A Comprehensive Review On Recent Advances in Preparation, Physicochemical Characterization, and Bioengineering Applications of Biopolymers

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Polymer Bulletin (2023) 80:7247–7312

https://doi.org/10.1007/s00289-022-04443-4

REVIEW PAPER

A comprehensive review on recent advances


in preparation, physicochemical characterization,
and bioengineering applications of biopolymers

Abinash Das1 · Togam Ringu1 · Sampad Ghosh2 · Nabakumar Pramanik1

Received: 28 March 2022 / Revised: 20 July 2022 / Accepted: 15 August 2022 /


Published online: 25 August 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022

Abstract
Biopolymers are mainly the polymers which are created or obtained from living
creatures such as plants and bacteria rather than petroleum, which has traditionally
been the source of polymers. Biopolymers are chain-like molecules composed of
repeated chemical blocks derived from renewable resources that may decay in the
environment. The usage of biomaterials is becoming more popular as a means of
reducing the use of non-renewable resources and reducing environmental pollu-
tion produced by synthetic materials. Biopolymers’ biodegradability and non-toxic
nature help to maintain our environment clean and safe. This study discusses how
to improve the mechanical and physical characteristics of biopolymers, particularly
in the realm of bioengineering. The paper begins with a fundamental introduction
and progresses to a detailed examination of synthesis and a unique investigation of
several recent focused biopolymers with mechanical, physical, and biological char-
acterization. Biopolymers’ unique non-toxicity, biodegradability, biocompatibility,
and eco-friendly features are boosting their applications, especially in bioengineer-
ing fields, including agriculture, pharmaceuticals, biomedical, ecological, industrial,
aqua treatment, and food packaging, among others, at the end of this paper. The pur-
pose of this paper is to provide an overview of the relevance of biopolymers in smart
and novel bioengineering applications.

* Nabakumar Pramanik
[email protected]
1
Department of Chemistry, National Institute of Technology, Arunachal Pradesh, Jote,
Arunachal Pradesh 791113, India
2
Department of Chemistry, Nalanda College of Engineering, Nalanda, Bihar 803108, India

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7248 Polymer Bulletin (2023) 80:7247–7312

Graphical abstract

The Graphical abstract represents the biological sources and applications of biopol-
ymers. Plants, bacteria, animals, agriculture wastes, and fossils are all biological
sources for biopolymers, which are chemically manufactured from biological mon-
omer units, including sugars, amino acids, natural fats and oils, and nucleotides.
Biopolymer modification (chemical or physical) is recognized as a crucial technique
for modifying physical and chemical characteristics, resulting in novel materials
with improved capabilities and allowing them to be explored to their full potential
in many fields of application such as tissue engineering, drug delivery, agriculture,
biomedical, food industries, and industrial applications.

Keywords Biopolymers · Biocompatibility · Biodegradation · Bioengineering ·


Pharmaceuticals · Eco-friendly

Abbreviations
PA Polyamide
PVC Polyvinylchloride
PP Polypropylene
PE Polyethylene
PMMA Poly(methyl methacrylate)
PGA Poly(glycolic acid)
PLA Poly(lactic acid)
PCL Polycaprolactone
PHB Polyhydroxy butyrate
PPF Polypropylene fumigates
PDS Polydioxanone
DS Degree of substation
DDSA Dodecenyl succinic anhydride
CDs Cyclodextrins
PPV Poly(p-phenylenevinylene)
POB Poly-3-hydroxybutyrate

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EPS Extracellular polymeric substances


ALE Alginate-like exopolymer
TC Cholesterol
AI Apolipoprotein
HDL Lipoprotein density
DDA Degree of deacetylation
DA Degree of acetylation
DOX Doxorubicin
HAp Hydroxyapatite
CS Chitosan
RSM Response surface method
TPS Thermoplastic starch
UDP-GLC Uridine diphosphate glucose
NC Nanocellulose
KGM Konjac glucomannan
KSAP KGM-based superabsorbent polymer
AA Acrylic acid
UV Ultraviolet
PU Polyurethane
KL Kraft lignin
WG Wheat gluten
HPLC High-performance liquid chromatography
GSE Grapefruit seed extract
HNT Halloysite nanotube
ST Starch
GL Glycerol
PLGA Poly(lactide-co-glycolic acid)
NPs Nanoparticles
RROP Radical ring opening polymerization
MDO 2-Methylene-1,3-dioxepane
ROP Ring-opening polymerization
PLLA Poly(L-lactide)
PDLA Poly(D-lactide)
PDLLA Poly(DL-lactide)
3D Three dimension
DMSO Dimethyl sulfoxide
DCs Dendritic cells
NMR Nuclear magnetic resonance
XRD X-ray diffraction
SEM Scanning electron microscope
TEM Transmission electron microscopy
FTIR Fourier transform infrared
ATR​ Attenuated total reflection
CMC Carboxymethyl cellulose
CNF Cellulose nanofibrils
BC Bacterial cellulose

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PAC Polyaluminum-chloride
COD Chemical oxygen demand
SS Suspended solids
PA Polyamide
PEGDA Poly(ethylene glycol) diacrylate
MCC Microcrystalline cellulose
BNC Bacterial nanocellulose
LDPE Low-density polyethylene
EAA Poly(ethyleneco-acrylic acid)
HPMC Hydroxy propyl methyl cellulose
CAB Cellulose acetate butyrate
PHAs Polyhydroxyalkanoates
PVAP Poly(vinyl alcohol phosphate)
TPP Tripolyphosphate
GSH Glutathione
PEG Poly(ethylene oxide)
CaP Calcium phosphate
SC Supercapacitor
PHA Polyhydroxyalkanoates
MO Methyl orange
GG Guar Gum
XG Xanthan Gum
CN Cellulose nitrate
MC Methyl cellulose
AgNPs Silver oxide nanoparticles
5-FU 5-Fluorouracil

Introduction

Monomers are simple building blocks. A polymer is a substance made up of a


large number of molecules with a high molecular mass. A polymer is created by
the repeating unit of a monomer chain, which can occur naturally (natural poly-
mer) or be created artificially (manmade polymer or synthetically derived poly-
mer). Biopolymers are natural polymers found in living organisms. A biopolymer
is a long chain molecule made up of monomeric components that are covalently
bound together to produce a biodegradable molecule. Plants, trees, microbes, and
other natural sources are the primary sources of biopolymers. Synthetic poly-
mers are simpler and more arbitrary than biopolymers, which are complex mol-
ecules with well-defined three-dimensional structures [1]. Renewable resources
are used to create a wide range of biopolymeric materials with various physical
and chemical characteristics. Nature contains lignin, starch, cellulose, hemicel-
luloses, and a variety of other biopolymers [2]. Biopolymer’s future demands on
manufacturers for novel materials are enormous. However, because the materi-
als are being given expressly for sustainable development, their cost-effectiveness
must improve. The qualities of these polymers should be used in applications that

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utilize novel materials, and products should be produced based on those features.
They are beginning to appear as a result of this for being more responsible in car-
ing for the planet we live in. New biodegradable polymers with good skeletal and
mechanical characteristics have been the focus of recent study. Biopolymers orig-
inating from natural organisms have been manufactured in enormous quantities.
The biodegradability of biopolymers has been linked to the presence of certain
microorganisms and enzymes with distinct degradable characteristics [3]. The
biodegradability of biopolymers is facile, because the biopolymers are bearing
the oxygen and nitrogen atom in their skeletal backbone. Biopolymer is converted
to ­CO2, water, biomass, humid water, and other natural components during bio-
degradation. Biodegradable polymers offer a wide range of applications in bioen-
gineering, including tissue engineering, drug delivery systems, and wound dress-
ing, among others [4]. Biopolymers have a distinctive helical structure, stiffness,
charge-free chains, and a strong resistance to salt and cold; thus, they thicken and
stabilize better under harsh pool conditions [5].

General conversion of monomer to polymer

Monomers are small molecules, most of which are organic, that may combine
with other monomers to produce larger molecules, known as polymers. Every
monomer molecule has the ability to make chemical connections with at least
two other monomers. Polymers are a type of synthetic material made up of sev-
eral smaller pieces known as monomers. Polymers are chains of monomeric units
with an undetermined number of them. Polymerization is a chemical reaction
in which a large number of monomer molecules combine to produce a polymer
(Fig. 1). A polymerization can yield macromolecules with a linear or branching
structure. They can also take the form of a three-dimensional complicated net-
work. The basic approach for converting monomer to polymer is shown in the
diagram depicted below.

Fig. 1  Polymerization of monomer to polymer

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Biopolymer and classification of biopolymers

Biopolymers are naturally occurring polymer found in living organisms such as


plants, animals, microbes and other natural sources. Biopolymers are basically clas-
sified according to their origins, into two groups, i.e., natural and synthetic biopoly-
mer and classified in Fig. 2.

Natural biopolymer

Natural biopolymer is a biopolymer that formed organically from living organisms.


Proteins and polysaccharides are biopolymers that fall under the category of natural
biopolymers [6].

Protein

Proteins are big, complex molecules that serve a number of important functions in
the human body. Proteins are made up of hundreds or thousands of smaller com-
ponents known as amino acids that are linked in lengthy chains. They perform the
majority of the work in cells and are essential for the construction, function, and
control of the body’s tissues and organs. A protein is made up of 20 distinct types
of amino acids that may be combined in different ways. Plant proteins, such as those

Monomers
(Basic Unit)

Polymers
(Occurs by Polymerization
of Monomers)

Biopolymers (naturally
occurring compounds produced
by green plants, animals,
microbes, and fungus during
their life cycles)

Natural Biopolymer Synthetic Biopolymer


(Produced by the (Man-made ,produces
organism's living cells) through abiotic chemical
routes)

Polysaccharides Bio- Degradable


Proteins chitosan, chitin, Non- Biodegradable
Biopolymer
Collagen, silk, alginic acid, Biopolymer
fibrinogens etc. starch, cellulose, PA, PVC, PP,
konjac, guar gum PE,PMMA, PGA, PLA, PCL,PHB,
etc. Polycarbonate, PPF, polydioxanone
Polyurethane etc. (PDS) etc.

Fig. 2  Classification of biopolymers

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Polymer Bulletin (2023) 80:7247–7312 7253

found in foods like wheat, corn, and soybeans, are more immunogenic than animal
proteins. Plant proteins have a low molecular weight and a large net negative charge,
which makes them ideal for effective medication delivery. Proteins are hydrophilic
in nature because they include polar amino acids, which attract cells sympatheti-
cally. Natural biopolymers such as collagen, silk, and fibrinogens are accessible;
commercially available collagens are utilized as injections for skin sensitization and
antibody responses, as well as immunological uses [7]. Proteins’ main structure is
made up of peptide bonds and disulfide bonds. A peptide bond is produced when the
carboxyl group of one molecule combines with the amino group of the other mole-
cule, releasing a molecule of water in the process ­(H2O). This is a condensation pro-
cess (also known as a dehydration synthesis reaction) that happens between amino
acids. The mechanism of a peptide bond is seen in the diagram below (Fig. 3).

Polysaccharide

Polysaccharides are lengthy chains of monosaccharides connected by glycosidic


linkages that our bodies normally employ for energy or to aid cellular structure. Chi-
tosan, chitin, alginic acid, starch, cellulose, konjac, and gums (guar gum, gum Ara-
bic, gum karaya, etc.) are examples of naturally occurring polysaccharides. Chitosan
is a natural polysaccharide with a wide range of uses in medication administration
and tissue engineering. In the food business, alginic acid is used extensively in food

Fig. 3  Peptide bond formation in protein biomolecules

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processing and manufacturing. Starch is a typical natural polysaccharide that is used


as a coating and adhesive because it is water-insoluble [8].

Synthetic biopolymer

Synthetic biopolymers are polymers that have been modified from natural polymers
or chemically produced from synthetic monomers such that they can degrade natu-
rally without leaving residues that are hazardous to living things and the ecosystem.
Synthetic biopolymers have received a lot of interest in recent years due to their
significant advantages over natural polymers in terms of stability and flexibility
to fit a wide range of applications. Synthetic biopolymers, on the other hand, are
preferred over synthetic polymers due to their biodegradable qualities and environ-
mental safety. Synthetic biopolymer synthesis may now be tuned to match specific
applications thanks to breakthroughs in new molecular designing tools and polymer
chemistry. Because of some of its unique qualities, including as stability, controlled
release, no immunogenicity, and removal from the body, synthetic biopolymers have
found one of their most important uses in the medical industry, which matches their
application in human bodies. In comparison with ceramic and metal particles, syn-
thetic biopolymers are easier to produce in many shapes and sizes. They are used
in industry and have cheap production costs, and they play a vital part in our daily
lives. Enzymes and live cells generally carry out biopolymer synthesis to the target
biopolymer molecules [9]. Synthetic biopolymers are generally classified into two
categories, i.e., non-biodegradable biopolymers and degradable biopolymers.

Non‑biodegradable biopolymer

Non-biodegradable polymers are those that are resistant to environmental break-


down and hence end up in the form of garbage. Non-biodegradable biopolymers
are resistant to the environment and are often used in non-biomedical applications.
Some common examples are PA, PVC, PP, PE, PMMA, polycarbonate, PU, etc.
[10].

Biodegradable biopolymer

Biodegradable polymers are those that breakdown when exposed to the elements.
Biopolymer’s biodegradability makes it a viable alternative for replacing petrochem-
ical-based packaging materials. Synthetically biodegradable polymers are made in a
controlled environment and have consistent skeletal and mechanical characteristics,
such as rigidity and accomplished modulus. When compared to biological scaffolds,
they are less expensive to make and promote contact with endothelial cells [11].
Artificially generated biodegradable synthetic polymers serve an important role in
tissue engineering and other biological fields. The decomposition of synthetic poly-
mers is accomplished by simple hydrolysis [12]. PGA, PLA, PCL, PHB, PPF, PDS,
etc., which are the synthetically biodegradable polymers have been used in medi-
cine and pharmaceuticals process. The hydrophilicity of PGA is extensively greater

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than that of PLA, leading to higher crystallinity; thus, it was used as evolutionary of
entire initially synthetic adsorbable structure [13].

Properties of biopolymers

Biopolymers are a type of polymer made from biological resources. Because of their
abundance, high tolerance, high thermal stability, non-toxicity, antibacterial activ-
ity, antifungal activity, biocompatibility, biodegradability, and other unique qualities
such as strong adsorption capacities and ease of functionalization, they have been
studied for a variety of applications in the industrial, biomedical, pharmaceutical,
drug-delivery, tissue engineering, medications, tablets, adhesives, paper, food, cot-
ton, and rayon sectors, including sorption [5].

Synthesis methods of biopolymers

Synthetic biopolymers are biopolymers that have been artificially modified by a


biotic chemical process. Biopolymer synthesis may be accomplished using a variety
of methods and techniques. Some typical biopolymer synthesis techniques for pro-
ducing well-generated structural and mechanical characteristics of biopolymer are
listed below

• Esterification of biopolymers
• Dehydration of biopolymers
• Polycondensation of biopolymers
• Hydrolysis of biopolymers
• Granulation of biopolymers etc.

Esterification of biopolymer

Esterification is a chemical process that occurs during the ester’s synthesis. Esterifi-
cation is a chemical reaction that produces an ester (RCOOR) and water by combin-
ing alcohol (ROH) with an organic acid (RCOOH). Through an esterification reac-
tion between a carboxylic acid and an alcohol, this chemical reaction produces at
least one ester product. The esterification of following biopolymer starch, cellulose,
and hemicelluloses is given below.

Esterification of cellulose

Esterification of cellulose occurs either in throughout polymeric chain or occurs at


outer cellulose thread to design cellulose ester. When enormous amounts of cel-
lulose are generated by a homogeneous or heterogeneous process, the surface is
altered. Cellulose nitrate (CN) is the most widely used inorganic cellulose ester,
with huge volumes generated in industry. It’s commonly found in plastics, coatings,

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explosives, and propellants, among other things. In heterogeneous equilibrium, the


esterification of cellulose nitrate is carried out by cellulose and a combination of
nitric acid and sulfuric acid with a degree of substitution (1.8–2.8). The heterogene-
ous direct reaction between cellulose and sulfuric acid is known as CS esterification.
Synthetic CS is formed through the displacement of an ether or ester group in cel-
lulose [14].

Esterification of starch

As an esterification reagent, acetic acid and acetic anhydride are used to make starch
acetate. The pH, time interval, and the presence of a catalytic agent all influence the
incorporation of acetyl groups into starch molecules. For low (0.01–0.2), medium
(0.2–1.5), and high (1.5–3) acetyl starch, the degree of substation (DS) ranges
from 0.01 to 0.2. The alkenyl succinic anhydride DDSA is a unique alkenyl suc-
cinic anhydride. The esterification of DDSA starch in an aqueous solution produces
a water-resistant product that is widely utilized in the film and paper industries [15].

Esterification of hemicellulose

Hemicellulose is a polymer present in plant dell cells and cell walls. Hemicelluloses,
a biopolymer used to make films and hydrogels, has been employed in biomedical
applications such as medication delivery and tissue engineering. Chemical synthe-
sis of hemicellulose yields furfural, xylitol, ethanol, and lactic acid. The eco-friend-
liness, low hydrophobicity, higher electrochemical and thermal balance, and faster
reaction rate of biomaterials such as cationic hemicelluloses, carboxymethyl hemi-
celluloses, lauroylated hemicelluloses, and acylated hemicelluloses are the homog-
enous upgradation of hemicellulose. The esterification of xylan-rich hemicelluloses
with maleic anhydride in the presence of a catalyst, LiOH, in an ionic liquid medium
under homogeneous conditions with a degree of substation (DS) of (0.095–0.75) has
a wide range of applications in agriculture, food, waste water treatment, and phar-
maceutical industries [16].

Dehydration of biopolymers

Trehalose’s exceptional performance as a cryo- and dehydroprotectant of fluctuating


systems is the dehydration of biopolymer. Cyclodextrins (CDs) have been employed
as a dehydrating agent to increase the mechanical potentiality of proteins using the
dehydration technique. Chemical conjugation between enzymes and CD deriva-
tives in aqueous medium leads in enhanced thermal stability of the enzymes due to
supramolecular superior reciprocal action on the enzyme surface. The bimolecular
of biopolymer is well protected by dehydration of the biopolymer [17]. Glass transi-
tion features are seen in the biopolymer polysaccharide. The glass transition affects
the thermal characteristics of native dehydrate biopolymers in a significant way [18].
The pace of dehydration is slowed by the evaporation of free water. Water diffusion
occurs in the liquid phase, the vapor phase, or both phases during the dehydration

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of biopolymers. The shrinking of the film during the dehydration process causes a
change in the structure of the polymer film. Adhesives, coatings, food industry, and
drug delivery in the pharmaceuticals sectors have all leveraged the kinetics of dehy-
dration of diverse biopolymers [19].

Polycondensation of biopolymers

Polycondensation is the process of combining different monomers to generate pol-


ymers. The process is frequently accompanied by the release of a variety of low-
molecular-weight sub­sidiary products (water, alcohol, and salt). The polyconden-
sation synthesis of biopolymers provides a flexible toll procedure for biopolymer
modification. Polycondensation of diols and diesters of H-phosphonic acid, phos-
phoric dihalides, or phosphoric acid can be used to make phosphorus-containing
polymers. In poly-condensation synthesis techniques, dihydroxy(oligolactide) and
ethyl dichlorophosphate react in solution to create bulk polilactofate [20]. In acidic
settings, polycondensation of water-soluble melamine/formaldehyde results in a gel
with a large spherical cavity. Melamine polycondensation and melamine replace-
ment with formaldehyde can also be utilized to generate more flexible foam and
fiber resins. In addition, monodisperse melamine/formaldehyde microspheres may
be made using the polycondensation method [21]. During the Knoevenagel poly-
condensation synthesis, where the backbone double bond substitution occurs, where
the modified PPV containing cyano groups has a higher electropolymerizing activity
[22].

Hydrolysis of biopolymer

The non-toxic properties of biopolymeric synthetic polymers are attributable to the


fact that they do not need the formation of hydrocarbons or carbon dioxides; their
breakdown produces water. The ultimate outcome is carbon dioxide, which is dam-
aging to human biology and globalization. Azotobacter maintains a critical role in
the creation of the synthetic biopolymer Poly-3-hydroxybutyrate (POB) through
hydrolytic modification. In the presence of phosphate buffer, the hydrolysis of POB
synthetic biopolymer forms a film at 70 °C. The temperature, incubation medium,
chemical content of the biopolymer, and molecular weight all influence the hydro-
lytic breakdown of POB. The hydrolysis of PBA occurs at the surface area during
the hydrolytic synthesis [23]. The biopolymer cellulose has a strong intermolecular
arrangement in its structural backbone, which gives it significant strength and resil-
ience to hydrolysis, whereas hemicellulose is random and amorphous in nature, with
little cohesiveness. Dehydration followed by hydrolysis reaction at critical water
condition was used to initiate thermal cleavage at one end of the cellulose biopoly-
meric chain. The bond brake occurs during the hydrolysis of cellulose at tempera-
tures of 200–350 °C in the presence or absence of a catalyst in a nitrogenic envi-
ronment. Lignin and hemicellulose are biopolymers that may be generated through
hydrolysis, which involves the breakdown of bonds around -critical water. In an
aqueous atmospheric solution, enzymatic hydrolysis of the cellulose biopolymer

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produces xylitol and furfural. In addition, hydrolysis is important in the destruc-


tion of lignin because the reaction medium is encouraged by the high ion product of
water [24].

Granulation of biopolymer

The biopolymer’s granular production method has become speculative and uncer-
tain. The bio granulation of biopolymers dominates the prospective applicabil-
ity, which includes greater toxicity tolerance, treatment of high-loaded carbon/
nutrient load pollutants, high-grade settleability, and increased biomass with hold-
ing, among other things [25]. Granulation produces EPS, which include proteins,
lipids, humic acids, polysaccharides, and nucleic acids that keep microorganisms
together. For full granulation of biopolymer, a long time period of roughly 308 days
is required, which accelerates through two phases, phase-1 and phase-2. Phase
1 takes day 0 ~ 182–220 for low granular mechanism, whereas phase 2 takes pale
after 182–220 days for steady granular mechanism. Granulation under local micro-
bial composition improves the stability of ALE, which aids in subsequent qualitative
research for industrial use [26].

Physical properties and geographical orientation of recent studied


biopolymers

Chitosan (CS)

Rouget, who discovered chitosan in 1859, discovered it when chitin was heated in
an alkaline medium. However, Hoppe-name Seyler’s was first used in 1894 [27].
CS is an a linear amino polysaccharide biopolymer derived naturally from shrimp
and crab exoskeletons. Hoppe-alkaline Seyler’s deacetylation of chitin to produce
chitosan. CS is a heterogeneous polymer with a well-defined chemical structure that
consists of 1–4 connected 2-acetamido-2-deoxy-β-D-glucopyranose and 2-amino-
2-deoxy-β-D-glucopyranose. The structure and processing of chitosan is given in
Fig. 4.
CS’s biocompatibility and degradability make it useful in biomedical applications
such as wound healing and tissue engineering. CS’s unique structural and antibac-
terial qualities make it suitable for use in film or membrane fabrication as well as
medication administration. Chitosan is water insoluble but soluble in acidic media.
In the presence of a nucleophilic amino group, Chitosan has three reactive groups
that cause a nucleophilic substitution process. CS’s potential actions, such as dis-
infection, non-toxicity, antibacterial, and antimicrobial qualities, make it a good fit
for biopesticides and the food industries as cited in Fig. 5 [28]. When human serum
albumin is exposed to peroxyl radicals, CS has a similar potency to vitamin C in that
it prevents the formation of carbonyl and hydroperoxide groups. Because CS has a
low molecular weight, it limits neutrophil activation and serum albumin oxidation,
which reduces oxidative stress. The availability of high molecular weight chitosan

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Fig. 4  Deacetylation of chitin forms chitosan

will lower cholesterol (TC) and apolipoprotein (AI) levels while increasing lipopro-
tein density (HDL) [29].
With increasing antimicrobial action, the degree of deacetylation (DDA) of CS
rises. CS is a biomolecule with a DDA of 70 percent or less, whereas water-soluble
chitosan has a DDA of 50 percent or less. Protonation is facilitated by the amino
group (R-NH2) rather than the acetamido group (R-NH-C(O)-CH3) at the ­C2 posi-
tion of chitosan, which has a higher DDA value. When the protonation half-life
period occurs, chitosan delivers a positive charge, resulting in a reduction in pH
when the protonated group attaches to its cytoskeletal molecular body [30]. CS is
a polysaccharide-rich in bonding hydrogen that degrades before reaching the glass
transition. CS solution is used to make films, gels, fibers, and sponges as a result of
this phenomenon. The dissociation potential of CS in acidic solution will be dem-
onstrated by its polyelectrolyte charters and polycationic nature (pKa). The value
of pKa at zero charge of chitosan varies from 6.46 to 7.32, depending on the degree
of acetylation (DA) [31]. CS, which is found in mango and also in guava, inhibits
the growth of bulk bacteria, resulting in a decrease in weight and respiration rate
[32]. CS-based hydrogels are used for sensory detection. Hydrogel is a biocom-
patible biopolymer with a high fluid absorbability property that may be utilized
to make a base biosensor. A CS-based hydrogel was used to detect certain target
chemicals electrochemically. Furthermore, because to their difficult cell–matrix

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Fig. 5  Life cycle of chitosan biopolymer

interaction, chitosan-based nanofibers play a significant role in drug delivery and tis-
sue engineering, as evidenced by the formation of doxorubicin (DOX)-incorporated
hydroxyapatite (HAp)-chitosan (CS) nanocomposite induced on osteosarcoma cells
[33]. Life cycle of other biopolymers is depicted in Figs. 6, 7, and 8.
CS derivatives are used in the textile industry for antimicrobial finishing of bioac-
tive textiles and in the paper industry to increase paper weight strength [34]. Because
the green biopolymer CS contains antibacterial agents, it limits surface contamina-
tion of meat and fish. According to recent study, the antibacterial capabilities of CS
film against L-monocytogenes make roast beef suitable for food consumption [35].
CS’s biocidal qualities have been employed to prevent the growth of spoilage micro-
organisms, making it useful for food preservation and food safety [36].

Gelatin

Gelatin is a macromolecular protein biopolymer that is formed by the perfect hydrol-


ysis of collagen. When compared to other naturally occurring biopolymers, it exhib-
its non-toxicity, a thermally reversible sol–gel transition, high mechanical strength,
high water solubility, and greater elastic characteristics [37]. Amino acids are linked
together through peptide linkage in the biopolymer gelatin’s structural makeup. The
chemical structure of gelatin is depicted in Fig. 9.

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Fig. 6  Life cycle of gelatin biopolymer

Fig. 7  Life cycle of cellulose

Gelatin is odorless and tasteless, and it is insoluble in acetone, chloroform, ether,


ethanol (95%), and methanol, but it is soluble in acids, alkalis, and glycerin. Gela-
tin biopolymer molecules are soft and swell due to their high absorption and water
binding capability. After full dissolution, the mixture of hot water and gelatin is

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Fig. 8  Life cycle of PLA

Fig. 9  Chemical structure of gelatin

cooled to form a jelly structure. In the presence of functional groups, gelatin biopol-
ymers’ particular properties to water produce hydrogels (OH, N ­ H2, COOH). The
hydrolytic reaction produces two forms of gelatins (A&B), which are generated by

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acidic hydrolysis of pig skin and basic hydrolysis of bones, with positive and nega-
tive properties for animal skins, respectively. At particular pH levels, the presence of
charge on the gelatin body affects biocompatibility [38, 39]. Recent study has shown
that gelatin produced from the kumakuma (Brachyplatystoma filamentosum) spe-
cies is suitable for response surface technique (RSM) [40]. Also, gelatin biopolymer
extraction from the lamina of lizard fish. In a conventional laboratory process, the
Zhou and Regenstein method will detect the percentage of yield concentration of
gelatin biopolymer, whereas the Biuret method using bovine serum albumin would
detect the concentration of protein in the extract solution [41]. Bovine and porcine
gelatin biopolymer are the most common sources for gelatin extraction and manu-
facture. Chitosan is utilized in vitamin encapsulation, plasma replacements, capsule
and tablet binder, and other biomedical science applications. The special qualities
of gelatin form gelation are employed in food sectors for chewing, gelling, sanitary
food packaging, and dairy product manufacture. It is also used to make film coat-
ings, printer ink, and colored sheets [42]. Biomimetically preparing gelatin and HAp
composites under coprecipitation results in well-organized pore architectures with
significant tissue scaffolding potential. Biopolymer gelatins have a higher propensity
for hydrophilicity and gas barrier, making them suitable for tissue engineering appli-
cations. However, their lower skeletal strength makes them unsuitable for usage in
packing materials [43].

Starch (ST)

ST is a natural biopolymer obtained from plant photosynthesis, by using carbon


dioxide and water as a basic supplement, providing energy to human beings. Entire
structural biodegradability, less price and suitable renewable properties of starch
have been used for developing of viable bio-based polymeric compounds. ST-
based biopolymeric materials has been successfully used for conservation of pet-
rochemical resources and decrease the harmful biological impact on atmosphere.
Ecofriendly and biodegradable polymeric behavior of starch molecules is used for
developing novel bioplastic polymeric materials. The modification of thermoplastic
starch (TPS) with different di-isocyanate derivatives will enhance the modulus and
tensile strength and hydrophobic nature of TPS promotes a bosting plasticizer [44].
ST molecules have complex helical structure made up of D-glucose units, bonded by
α-D (1–4) glucosidic linkage form linear polymeric backbone chain (amylase) and
α-D(1–4) linkage with α-D (1–6) linkage glucosidic backbone chain form branched
(amylopectin) represented in Fig. 10 [44, 45].
The biomolecule starch plays an essential part of the human food hierarchy
system. Tacca leontopetaloides is a Polynesian arrowroot starch that is related to
corn starch and belongs to the Dioscoreaceae family. Tacca starch contains 77.5%
amylopectin and 22.5 percent amylase. This ST is a perennial herb with a tuber-
ous rhizome that serves as a biocompatible processing substitute. Recent research
has shown that incorporating glycerol into tacca starch results in the development of
ecofriendly biodegradable polymers with poor specific resistance capabilities [46].

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Fig. 10  Basic chemical structure of starch biopolymer

The blend of ST-based polymer became poor, because of their immiscible


nature in biofield. So, ST-based biopolymer is needed to be modified chemically
for enhancing the supermolecular mechanical properties and extensional environ-
mental uses. The hydroxyl modification and graft copolymerization are the versatile
method for chemical modification of ST through by which its properties get change.
Biocompatibility uses of starch-g-polymer occur through graft copolymerization.
Also, starch-g-PCL and starch-g-PLA that are the graft co-polymer have been used
as direct thermoplastics and compatibilizer and are clearly biodegradable and reveal
supermechanical supports [47].
ST is the prevalent carbohydrate stored in many plants like potato, tapioca, corn-
starch, wheat etc. The biopolymer starch has semicrystalline morphology with
distinctive degree of crystallinity. Amylose and amylopectin are the two leading
ingredients of starch bio- molecules with linear linkage. ST without accumulative
is biodegradable and non-toxic and performs excellent biocompatibility. ST is a
most common present biomolecule which is capable of switching synthetic poly-
mer. The biomolecule starch was discovered as an applicable agent for the polyester
fiber assembly. Spinning technology has been used for modification of fiber based
starch molecules. Wet spinning technology was liable to eject the contents of aque-
ous starch dispersion and glycerol in a methanol/glycerol coagulation bath to accom-
plished starch fibers. According to the study, the melted thermoplastic ST eject
through a spinneret to produce filaments for fabrications. Fiber spinning is carried
out by using distinct plasticizer and used melt spinning technology. Recent research
has been proved that the assembly of ST filaments, by using mixture of ST, water,
plasticizers and other alternative supplement through electrospinning technology
[48]. ST-based modified substances have low water accomplished attribution and
week mechanical support, as analyze to synthetic polymer due to their high hydro-
philicity and water binding capacity. It has been found that the film made by mixture
of urea plasticizer and corn starch is resulting, enhance of mechanical strength of

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starch by increasing the urea plasticizer concentration within that film [49]. Phlo-
roglucinol, also known as 1,3,5-trihydroxybenzene, is a phenolic compound that is
antagonistic to marine brown seaweeds (phaeophyceae). In the perinuclear region of
microbes, acetyl-malonate is used in the biosynthesis of phloroglucinol. Phloroglu-
cinol monomeric units bind together to form the backbone of over 700 secondary
metabolites. Antiplasmodic, antibacterial, antiviral, antimalarial, antioxidant, anti-
depressant, and anticarcinogenic properties have been demonstrated for phloroglu-
cinol and its derivatives. The encapsulation of soluble starch provides significant
protection to phloroglucinol, extending its control release potential [50].

Cellulose

Cellulose is a molecule made up of hundreds, if not thousands, of carbon, hydrogen,


and oxygen atoms. Cellulose is the main substance in plant cell walls, which helps
plants stay stiff and upright. Although cellulose cannot be metabolized by humans, it
is essential in the diet as a source of fiber. Anselme Payene was the first to discover
cellulose. Due to their biocompatibility and ecological livable, cellulose and its
derivatives are attracting increasing immersion and are thought to have big implica-
tions. It is critical nowadays to keep packaged food from spoiling. Particularly in the
current COVID-19 pandemic situation, where industries, workers, and transporta-
tion are completely shut down, certain premeditated strategies to prevent food waste
and degradation are required. As a result, the material used in food packaging can
help to keep food from spoiling. Cellulose is a low-cost element with high mechani-
cal strength and a high demand in the global market, particularly in the food and
textile industries [51, 52]. The chemical structure of cellulose and its intramolecular
hydrogen bonding is given in Fig. 11.
Cellulose is polymerized by organisms other than plants. Bacteria are also
able to generate the polysaccharide. Acetobacter xylinum has been the most
extensively studied bacterial cellulose synthesis. The physiochemical influence
of bacteria-produced cellulose is assumed to be used to aid in flocculation or to
preserve specific environments, such as aerobic environment or allowing connec-
tion to plants. Bacterial cellulose is assembled similarly to plant cellulose, with

Fig. 11  Structure of cellulose

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polysaccharide chains forming microfibrils and microfibril bundles forming rib-


bons. Bacterial cellulose, unlike plant-based cellulose, is highly pure and does
not require separation from lignin during processing. In addition, bacterial cel-
lulose has excellent moisture absorption properties to plant cellulose; plant cel-
lulose has a water holding capacity value of 60%, whereas bacterial cellulose can
hold water up to 1000% of the cellulose specimen. Bacterial cellulose’s superior
water weight permits the polymer to have high crystallinity while remaining
seamless and malleable, increasing its viability for therapeutic diagnostics such
as building elements of artificial abdominal organs and blood vessels. In plants,
cellulose syntheses is a challenging of enzymes that encompasses the entire cell
membrane; in bacteria, it covered the whole cell wall. Uridine diphosphate glu-
cose (UDP-GLC) is an essential cofactor in the synthesis of cellulose including
both plants and bacteria. The cellulose synthase comprehensive takes the glucose
monomers from UDP-GLC, carries it all over the cell membrane or cell wall, and
attaches it to the incipient extracellular cellulose backbone chain [53–56].
The production of nanocellulose microfibers from cellulose biopolymer occurs
through the use of acid hydrolysis methods and analytical techniques, which
result in a high surface area and homogeneous communication with the polymeric
resins. The microfiber nanocellulose (NC) was created by polymerizing micro
limpid cellulose with a routine method that did not require the use of any harmful
chemicals such as sulfuric acid or hydrochloric acid. The bionanocomposite film
based on agar-nanocellulose, which is totally biocompatible and biodegradable,
has a significant potential for use in biodegradable packaged foods or bio sensing
applications [57].
Due to their adequate mechanical and physical properties, cellulose and its
variants have sparked significant interest as biocompatible polymers for advance-
ments in the biomedical field. By taking advantage of its hierarchical structure,
cellulose innately develops functionality, flexibility, and high specific strength.
It is also low in density, low in cost, and biodegradable. Cellulosic materials
allow for the fine-tuning of permeability and interdependences, both of which
are beneficial for biological and biomedical applications. Conventionally, cellu-
losic resources have been used in companies to develop paper and textiles, but in
recent decades, cellulosic ingredients have been used for a wide range of appli-
cations, including tissue engineering applications [58]. Because of their cyto-
compatibility, good biocompatibility, biodegradability, and minimal side effects,
cellulosic materials in particular hold great potential as cost-effective forward-
looking materials for biomedical applications. Cellulosic components can also be
conveniently developed to produce high-quality substances due to their chemi-
cal features and functions. Mechanisms are shown conventional disease surveil-
lance but also medic-care relies heavily on cellulosic natural resins. Meantime,
many emerging application regions, such as tissue engineering, wound healing,
enzymatic manipulation, and drug carriers, are being investigated. The results of
extensive examination on cellulose from numerous sources and the preparation
of cellulose derivatives, as well as their applications as innovative medical and
biological ingredients in the fields of tissue regeneration, antiseptics, and drug
delivery etc. health related resources.

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Fig. 12  The fundamental biochemical structure of cellulose derivatives can be mono-, di-, or tri-substi-
tuted depending on -R group

Table 1  There are a variety Cellulose derivatives Functional groups (R)


of -R groups that are capable
of occurring in molecules of Cellulose acetate H, ­C2H3O
cellulose derivatives
Cellulose sulfate H, ­SO3H
Cellulose nitrate H, ­NO2
Carboxymethyl cellulose H, ­CH2CO2H
Ethyl cellulose H, ­CH2CH3
Methyl cellulose H, ­CH3

Derivatives of cellulose

Cellulose derivatives are a feasible alternative to pure cellulose because of their


greater dissolving capabilities. Ethanolic or aqueous hydrolysis may also convert
them to cellulose, which can then be used to make paper. Cellulose esters (cellulose
acetate), ethers (carboxymethyl cellulose, methyl cellulose, and ethyl cellulose), cel-
lulose sulfate, and CN are the most well-known cellulose derivatives, although oth-
ers exist (Fig. 12, Table 1). Various cellulose derivatives have been produced and
used in biomedical sectors to increase the value or broaden the adaptability of cel-
lulose. The functionalization pattern throughout the polymer chain affects the char-
acteristics of cellulose derivatives in addition to the type and degree of substitution.
Because of cellulose’s low solubility in organic solvents and its bulky and stiff main
chain, it is difficult to synthesize certain cellulose derivatives regio-selectively. On
the cellulose chain, the hydroxyl group is the most reactive and may be targeted for
reaction. It is difficult to take advantage of the modest reactivity variations between
the 2-, 3-, and 6-OH groups because cellulose hydroxyl groups are generally weak
nucleophiles. Excipients, filtration membranes, wound dressings, bioadhesives, and
drug delivery systems are just some of the many uses of cellulose derivatives in the
cosmetic and pharmaceutical industries.

Cellulose sulfate Cellulose sulfate has unique biological characteristics and is a


semi-synthesized cellulose derivative with a simple chain structure. It is an ester
of cellulose that may be generated using heterogeneous, homogeneous, or quasi-

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homogeneous sulfation processes. Water solubility and antibacterial capabilities


at high concentrations are two benefits of cellulose sulfate over virgin cellulose.
For heterogeneous sulfation of cellulose, H ­ 2SO4 and propanol are the most often
employed reactants In order to synthesize cellulose sulfate using S ­ O3-complexes
as a reactant, N
­ 2O4/DMF was employed, which has equal distribution, strong solu-
bility, and minimal chain degradation. Cellulose acetate is a chemical that might
be used to synthesize cellulose sulfate because of its high solubility in reactants
and ease of purification [59].
Cellulose sulfate has well-defined structure and absence of polymer chain
branching, cellulose sulfate is ideal for quality control and study into the rela-
tionship between structure and activity. Cellulose sulfate has been discovered to
have a stronger anticoagulant activity than heparin in their experimental settings,
and in vivo investigations have shown that the anticoagulation activity of this
compound was accomplished by speeding the inhabitation of antithrombin III on
coagulation components in plasma.
Recent study has found that the microencapsulation benefits from cellulose
sulfate generated in a homogenous process because of its high viscosity, strong
water solubility, and consistent sulfate group distribution. Novel research shows
was discovered that the chitosan-cellulose sulfate system might be utilized to
carry drugs directly to the colon, where they would be destroyed by bacteria
present in the colon, rather than the bloodstream. A study has demonstrated that
cellulosic sulfate may be useful in the control of cell activity. As a result, it is
a potential material for cell immobilization/encapsulation, which protects cells
from the external environment and provides a milieu for cell promotion, and con-
trols cell survival, proliferation, and the release of therapeutic compounds.

Cellulose nitrate Cellulose nitrate (CN) is a polynitrate ester that is derived from
cellulose. Its structure typically contains 2.2–2.8 nitrate groups for per glucose
unit. A powerful nitrating agent is used to nitrate cellulose derived from wood pulp
or cotton linters (e.g., nitric acid). The electrophilic assault of ­NO2+ ions on the
OH moieties of cellulose replaces the hydroxyl groups with nitrate esters during
the nitration process.
The use of commercial lateral flow assay (LFA) kits, which are based on anti-
bodies or nucleic acids immobilized on a CN membrane, makes it possible to
identify particular biomolecules within the materials that are being examined.
This makes it possible to provide an accessible platform for prenatal testing, test-
ing for oncogene mutations, the diagnosis of infectious disorders, and the identi-
fication of microorganisms. NC/PCL membranes are utilized in bioengineering
for the detection of Zika virus and enzyme-linked immunosorbent assays, among
other applications (ELISA) [60].

Methyl cellulose Methyl cellulose (MC) is a major cellulose ether. MC is the sim-
plest alkyl ether that may be made in an alkaline media using a methylating agent,
such as methyl chloride or dimethyl sulfate. No matter how much you substitute
for the water in an organic solvent, you’ll still be able to dissolve methyl cellulose.

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For example, MC dissolves in water when the degree of substitution is between 1.4
and 2.0, and it is typically soluble in water and several organic solvents when this
degree is between 2.4 and 2.8.
During the hydrogelation process, silver oxide nanoparticles (AgNPs)
were synthesized in situ from Ag + ions using a silver acetate precursor salt
­(CH3COOAg). Both the burn wounds and the skin regeneration were improved by
the use of hybrid materials that were successfully evaluated. Post-surgery tissue
adhesion is minimized thanks to the polymeric blend’s lubricant coatings, such as
those seen on the CMC/PEG/MC composites.
It is also beneficial for medication delivery systems because of its role as an
emulsifying agent. For biological applications such as tissue engineering, wound
healing, and pharmaceutical formulations, methyl cellulose is most often utilized
[61].

Carboxymethyl cellulose Carboxymethyl cellulose (CMC), one of the most sig-


nificant cellulose ethers, is made by treating raw cellulose with sodium hydrox-
ide, extracting the alkali cellulose, and reacting it with monochloroacetic acid or
sodium monochloroacetate in an alcohol medium.
The biomedical field can benefit from the application of CMC as a viscosity-
increasing agent, rheological control agent, binder, stabilizer, and film forming,
especially in drug delivery and tissue engineering systems. Many biological uses
of CMC and NaCMC have been investigated because of their excellent gelation
ability and pH-sensitive swelling capabilities, notably the development of smart
stimuli responsive hydrogels for controlled drug administration. This new study
shows how to make hydrogels with redox and pH-responsive behavior, better
mechanical characteristics and swellability by cross-linking CMC/quaternized
chitosan (HACC) hydrogels. 5-Fluorouracil (5-FU), a broad-spectrum antican-
cer drug, was included into the composite hydrogels. Under physiological set-
tings (pH 7.4), the model drug’s release was maintained, but it was accelerated
in an acidic or reducing environment. Because of its cheap cost, biodegradabil-
ity, biocompatibility, non-toxicity, and minor immunogenicity, CMC has been
extensively employed in tissue engineering applications. Biomimetic CMC/dopa-
mine tissue adhesive hydrogels were inspired by mussel sticky proteins. Due to
the interfacial interactions between the catechol moieties of the hydrogel and the
biomolecules on the wet tissue surface, the materials had a six-fold increased wet
tissue adhesion force over a commercial suture agent (fibrin glue). Furthermore,
the gels showed excellent biodegradation and biocompatibility.
As a result of recent reports that CMC has the capacity to promote bone
growth, several investigations have been undertaken on its bone tissue engineer-
ing applications. Using calcium phosphate (CaP)-loaded NaCMC nonwoven
sheets made by immersing protonated CMC alternately in calcium chloride and
sodium phosphate solution, researchers looked at how well they might stimulate
osteoblast development and bone repair in vivo. Even after lengthy storage at
room temperature, CMC provides a good support for protein and enzyme immo-
bilization [62].

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Konjac glucomannan (KGM)

Konjac glucomannan (KGM) is the key ingredient of konjac tubers, which are a
longstanding Araceae plant. Konjac glucomannan has been shown in biomedical
studies to improve health by limiting cholesterol in the blood and striving to improve
carbohydrate metabolic activity, bowel movement, and colonic ecosystems. KGM
is a staple ingredient that is commonly used to thicken and bind gravies, curries,
sauces, animal fat, and livestock. In an alkaline medium or when coupled with
certain other hydrocolloids like as xanthan gum or k-carrageenan, KGM can form
hydro gel. These gels are essential building blocks in a variety of food implementa-
tions, including jelly, noodles, tofu, and snacks. Collagen and KGM have been used
to transport drugs in living organisms. The combined emulsion effect of collagen
and konjac glucomannan can improve collagen dissolution in aqueous. The physical
properties of collagen, KGM, polyphenols, and ginsenoside Rb1 with polyphenols
and ginsenoside Rb1 may influence the ability to control release of drug. Further-
more, the appearance of these polymers in the complex can aid in the bioactivity and
storage of polyphenols and ginsenoside [63].
KGM is a naturally existing substance polysaccharide retrieved from the tubers of
Amorphophallus konjac. It is a copolymer made up of of β-(1,4)-linked D-glucose
and D-mannose residues in a molar ratio of 1:1.6 with a lower degree of acetyl moi-
eties at the C-6 position (1 in 17 residues, approximately). The structural representa-
tion of KGM is given in Fig. 13.
Because of the appearance of very active primary hydroxyl (­CH2OH) func-
tional groups at the C-6 position of KGM, a variety of chemical treatment, includ-
ing graft polymerization, are conceivable. KGM is extensively used in pharmaceuti-
cal and food applications due to its high viscosity, extremely good water retention
capabilities, gelling potency, non-toxicity, biocompatibility and biodegradability.
Recently, a KGM-based superabsorbent polymer (KSAP) was created by grafting
acrylic acid (AA) onto a KGM template and irradiating it with 60Co-g at room tem-
perature. FTIR spectroscopy and SEM imaging data analysis were used to character-
ize KSAP. The transplant of AA onto KGM was revealed by the large effect in bands
in the FTIR spectra of KSAP, KGM, and AA. XRD patterns revealed that crystalline
structure in KSAP was lower than in native KGM. SEM images revealed a rough
surface in the case of KGM and a micro porosity in the case of KSAP. The relatively

Fig. 13  Structure of Konjac glucomannan (KGM)

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hydrophilic nature of KSAP resulted in greater velocity and abilities for water
absorption. Graft copolymers compiled with an amount of radiation of 5.0 kGy and
a monomer to KGM ratio of 5 could accumulate 625 times their dry weight in water.
Ions, especially multivalent positively charged ions, considerably lowered KSAP’s
water permeability power [64]. In comparison with many other thermoreversible
gels, KGM forms a thermally balance gel after the addition of an alkaline agglom-
eration, and the gelation of KGM is aided by heating. Gelation happen as a conse-
quence of the arrangement of a network structure of crossing zones that are thought
to be established by hydrogen bonding. The green pharmaceutical characteristics of
KGM that contribute for its behavior in nanotechnology based drug delivery mecha-
nism include its elevated concentrations of mannose, which effectually enables the
communication of KGM with biotic surfaces that really are extremely lucrative in
mannose synapses, such as M-cells enveloping Peyer’s fragments and phagocyto-
sis. Ionic gelatinization of chitosan with TPP (chitosan/TPP ratio values of 3/1 and
6/1) yielded chitosan nanoparticles [65, 66]. By solubilizing phosphorylated KGM
in the nanoparticle rescinding medium, it was possible to incorporate it onto the
nanoparticle configuration. Intra—molecular hydrogen bonds, as well as electro-
static interactions among oppositely charged groups in phosphorylated KGM deriva-
tive and free – ­NH3+ in chitosan, are responsible for the heterotypic relationship in
this co-gelled system. As the chitosan/konjac glucomannan ratio changes from 6/6
to 6/24, the nanoparticles’ hydrodynamic diameter decreases from 800 to 400 nm.
Regardless of the CS/ KGM ratio, the zeta potential of these nanoparticles was close
to the expected neutral value, ranging from − 0.4 to − 2.3 mV for about the same
content. This has been explained as a result of the plant polysaccharide shielding the
chitosan charges. The addition of KGM fiber to a diet may enhance metabolic func-
tional capacity in humans, and rats with low levels of KGM have lower plasma cho-
lesterol. KGM can also be fabricated into films or formed into blend film for coating
and packaging implementations, and KGM gels have considerable potential applica-
tions in a controlled release matrix [67, 68].

Lignin

Lignin is the second most prevalent biomaterial in plant species after cellulose and
is a fundamental natural biopolymer found in the cell walls of woody materials. This
is one of the basic components with a high potential for use in the production of
bio fuels, and it can be used as an operational polymer in the synthesis of bio-based
polymer blends [69].
Lignin is among the most common natural polymer found in plants. Lignin,
the second most prevalent renewable bio-resource after cellulose, is regarded as
a solid waste in a variety of industrial processes. Attempts to valorize lignin have
been posted in a large number of articles and reports in recent years. The significant
characteristics of lignin, such as its abundance, inexpensive, and biodegradability,
increasing carbon content, aromaticity, and reinforcing abilities, make it an excel-
lent candidate as a potential component for bio-composites. Over 50 million tons of
lignin are produced as a by-product of bio refineries each year, with 98 percent of it

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being burned to generate energy. Only 2% of the lignin has been used for other pur-
poses, primarily as dispersants, adhesives, and fillers. Commercial lignin consists
primarily of lignosulfonates from sulfite pulp mills (approximately 1 mill. ton/year)
and less than 100,000 tons/year of Kraft lignin (KL) [70].
Depending on the application, lignin can be used as a factor in biocomposites
with or without modification. Acetylated KL was used to optimize its affinity with
PLA. The incarnation of Kraft lignin, on the other hand, diminished the tensile ulti-
mate strength of the PLA with rising lignin loadings of 10% and 20%. Additionally,
when acetylated lignin was combined with a thermoplastic, the tensile strength was
increased. Lignin can be integrated directly into a polymeric matrix without recon-
figuration, such as a UV-light stabilizer, antioxidant, flame retardant, plasticizer, and
flow enhancer, to reduce the cost of manufacture, plastic, and potentially enhance
mechanical characteristics. Lignin can also be used as a coupling agent in bio com-
posites made from natural fibers. Lignin can act as a cross-linking agent between
hydrophilic fibers and hydrophobic matrix polymers, thereby reinforcing the fiber
matrix interface. Lignin therapies of hemp and flax fibers have been shown to
improve the compatibility of the fibers with the thermoset matrix, thereby enhancing
the mechanical strength of the biocomposites. When compression-molded PLA-cot-
ton composites were treated with lignin, the tensile properties improved. Lignins are
formed through the polymerization of cinnamyl alcohols (monolignols), the struc-
ture of which varies depending on the plant type Coniferous wood lignin is almost
entirely composed of coniferyl alcohol (G-units), with minor amounts of coumaryl
alcohol (H-units) present. The latter, on the other hand, is a major component of
condensing wood lignin. In wood fibers, however, both coniferyl alcohol and sinapyl
alcohol (S-units) are used as building blocks, and all three alcohols are used as
lignin precursors in monocotyledonous tissue [71, 72]. The chemical structure of
lignin is given in Fig. 14.
Coniferous wood lignin is almost entirely made up of coniferyl alcohol (G-units),
with only trace amounts of coumaryl alcohol (H-units). In contrast, the latter is a
crucial constituent of condensing wood lignin. Coniferyl alcohol and sinapyl alcohol
(S-units) are both used as fundamental building blocks in wood fibers, and all three
alcohols are lignin blueprints in monocotyledonous tissue [72].
The polyurethane (PU) reaction is used to stabilize the soil for building engineer-
ing, in which two types of solution were implanted deep into the earth before tun-
neling and then the soil was exhumed after the reaction was completed. This strat-
egy is beneficial when removing a large amount of soil with an excavator because it
relieves the risk of collapse. However, the eliminated soil that has been cross-linked
by synthetic polymers is not biodegradable. To address the aforementioned issue, an
attempt was made to use lignin polyol to stabilize sand. The quantity of lignin polyol
used is less than 5% of the total sand, and a crystallized sand block can be obtained.
It has also attempted to develop PU composite encapsulated fertilizers that can be
kept in the soil for a longer period of time by releasing slowly [73].
The Mannich reaction was used to make a low-cost, environmentally friendly,
and magnetic lignin-based nano-adsorbent. Phosphate was effectively removed from
solution via adsorption. Furthermore, the nutrients in magnetic adsorbent nanoparti-
cles, such as recycled phosphate and chelated iron, can be reused as a multielement

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Fig. 14  Structure of lignin biopolymer

fertilizer. The release behaviors revealed that the Fe and phosphorus release rates
from M/ALFeP increased steadily over time, reaching 69.1% and 67.2 percent after
30 days in neutral soil, respectively. Batch experiments on cycle adsorption revealed
that M/ALFe has good recyclability and reusability, lowering costs and avoiding soil
pollution. As a result, a method for making lignin-based high-value-added nanoma-
terials in wastewater treatment has been developed, and phosphate-laden nanoparti-
cles as Nano fertilizers show promise in sustainable agriculture [74]. A number of
bio-based composites based on starch, lignin and cellulose were fabricated from an
ionic liquid, 1-allyl-3-methylimidazolium chloride and coagulated in a system with-
out solvent. The study found that the mechanical strength of the biocomposites was
evidently depending on the contents of lignin, starch and cellulose, resulting from
the mutual supplement among different components. High gas barrier ability and
great thermal stability were clearly observed in the biocomposites. Holocellulose
and acid insoluble lignin of Pecan nutshell fiber were utilized as reinforcements of
PLA-based bioplastics. Because of its radical scavenging activity, lignin can act as a
stabilizer in protein-lignin bioplastics. Thermal molding was used to incorporate KL
and WG into materials. During material mixing, the results suggested that KL has a
radical phagocytic action toward thiyl radicals.
The good connection of WG and KL was confirmed by size isolation HPLC. To
improve the physical and functional properties of the bioplastics, different concen-
trations of alkali lignin and lignosulfonates were added to enzymatically modified

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Fig. 15  Structure of agar

Fig. 16  Structure of agarose

soy protein. Alkaline lignin and lignosulfonates showed typical radical scouting
activity when compared to commercial butylated hydroxytoluene, suggesting that
they could be used in active packaging. The blends with alkaline lignin had a strong
UV-blocking ability due to the color of the lignin. Thermal stability and tensile sta-
bility of the lignin-added films were significantly improved when compared to the
control films without lignin [75].

Agar

Agar is a polysaccharide mixture made composed of agarose and agaropectin with


carrageenan-like functional characteristics. It is largely derived from red algal cell
walls. They are recovered in the same way as carrageenans are: with hot water.
Agars are employed as emulsion and suspension stabilizers and gelling agents, simi-
lar to carrageenans. Agar is utilized in the food sector for around 90% of its output;
the rest is used to create capsules for clinical use and as a medium for bioreactors
for cell and tissue development. Agar contains a few bioactive characteristics and
modulates UV light absorption [76, 77].
These are members of the Rhodophyceae family of red seaweeds. Agarose, which
is responsible for gelling, makes up the majority of agar. Its structural unit is made
up of (1–4) linked 3,6-anhydro-a-L-galactose and (1–3) connected b-D-galactose
units that alternate. The structures of agar and agarose are given in Figs. 15 and 16.
It is among the natural polymers with the strongest mechanical properties. Micro-
bial growth has little effect on the gel since agar is not enzymatically degradable by

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most bacterial species. As a result, it will remain stable, and microbial deterioration
will be low. Its high crystallinity guarantees a high level of strength and stiffness.
The food-grade agar used in this investigation was made by Urban Platter in Mum-
bai, India. Gelation hysteresis is a unique feature of agar biopolymer. As a result,
the temperatures at which it melts and gels varies significantly. The temperature at
which agar begins to dissolve in water is roughly 85 °C, while the actual temperature
varies depending on the agar source. When the temperature goes below 30–40 °C,
the viscosity of an agar solution increases, and it forms a stiff unyielding gel. By
combining agar with soil in the form of a heated solution and enabling it to gel
within the porous medium of the soil sample, this feature of agar was used to gener-
ate homogeneous soil specimens [78, 79].
The biopolymer agar has lately been investigated for soil erosion management
and improved hydraulic conductivity. Among biopolymers, agar has the maximum
mechanical strength. Within the soil mass, it can create a three-dimensional gel net-
work, forming a thick film and covering the soil particles. Furthermore, the agar
biopolymer’s complicated structure assures that it is less biodegradable. It has a long
history of safe food consumption, which supports its environmental friendliness
[80].
Seaweed-based nanoparticles were utilized to construct and test the effect of
using seaweed nanoparticles filler in agar-based biopolymer composite on improv-
ing physical water vapor barrier, mechanical, and biodegradable qualities, according
to recent research. When agar-based biopolymer is reinforced with seaweed nano-
particles, the characteristics of the biopolymer alter, although there are no visible
changes in the water vapor transfer rate (WVTR). The mechanical strength of the
agar-based biopolymer was increased by increasing the concentration of seaweed
nanoparticles, indicating that the agar-based biopolymer composite incorporating
seaweed nanoparticles could be used in food industrial applications such as food
packaging to replace petrochemical-based plastics [81].
Proteins (beans, seaweeds like agar–agar, and seeds), starches (pectins and gums),
and certain other plant tissues are employed to stabilize emulsions in longer-lasting
suspensions. Dressings, frozen desserts, jellies, mousses, pickles, puddings, salad
dressings, sauces, and yoghurt are all common uses for stabilizers [82].
Agar is the most often used microorganism growth medium. Because of the ease
with which agar may be moved (dry, dissolved, and gelled), it is widely used in
modern laboratories. When fed with adequate nutrients, solid agar plates can pro-
mote microbial growth or be used for antibiotic selection. Agar medium is vital for
the study of microorganisms and molecular biology, and it is frequently employed
in pathogen cultivation and detection from contaminated food and water [83]. Agar
is also commonly employed in biomolecular separation and purification due to its
porous 3D architecture. Agar is a basic medium that is commonly used in gel elec-
trophoresis, gel bead chromatography, and size exclusion chromatography. Aside
from being used as a solid growth medium, agar has been manufactured in various
forms (e.g., microspheres and films) to encapsulate molecules for continuous drug
administration or to immobilize proteins for tissue engineering. Because of agar’s
gelation capability, it is most commonly utilized as a hydrogel. To provide long-term
medication administration, agar hydrogels were modified by including additional

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7276 Polymer Bulletin (2023) 80:7247–7312

Fig. 17  Chemical backbone structure of PVA

Fig. 18  Synthesis of PVA

biopolymers to build an interpenetrating network. This agar hydrogel network topol-


ogy can increase the mechanical properties of drug delivery devices while also
extending the drug release profile. Agar hydrogels with high porosity have demon-
strated encouraging outcomes in tissue engineering for promoting cell adhesion and
proliferation [84, 85].

Poly(vinyl alcohol)

Herrman and Haehnel developed poly(vinyl alcohol) (PVA) in 1928, which is an


odorless and tasteless transparent white or cream-colored granular powder. PVA is a
non-toxic, semicrystalline, biocompatible, and biodegradable polymer that is soluble
in water. Textile sizing, paper coating, flexible water-soluble packaging films, con-
trolled drug administration systems, dialysis membrane, wound dressing, and arti-
ficial skin are just a few of the uses. Due to its remarkable qualities, such as strong
oxygen and aroma barrier capabilities, high tensile strength and flexibility, and great
film building, emulsifying, and adhesive properties, it has a broad range of applica-
tions. The fully hydrolyzed and partially hydrolyzed grades of PVA have melting
points of 230 °C and 180–190 °C, respectively. It may pyrolyze at high temperatures
and has a decomposition temperature of around 200 °C [86, 87].The chemical back-
bone structure of PVA is given below (Fig. 17).
PVA is a thermoplastic biopolymer made from the hydrolysis of the polyvinyl
acetate precursor. The following is the PVA synthesis (Fig. 18):

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Polymer Bulletin (2023) 80:7247–7312 7277

The activity of biological microbes degrades it. Because of its increased crystal-
linity, it is extremely soluble in water. Many polymer end goods, such as liquors,
surgical threads, and food packaging, are made with PVA. It is a polymer that is
strong, ductile, and extremely flexible. PVA is a biodegradable and non-toxic poly-
mer that is used in food packaging. Contact lenses, heart surgery, medication admin-
istration, and wound dressing are just a few examples of biomedical uses [88, 89].
Other polymers, such as food additives like citric acid, succinic acid, and tar-
taric acid, could be blended with the biopolymer PVA. In the packaging industry,
PVA blended with poly(3-hydroxybutyrate) (PHB) can be used. PVA/CS films have
mechanical, water vapor barrier, and antibacterial qualities that make them suitable
for use in food packaging. For food packaging applications, PVA has been investi-
gated active packaging with grapefruit seed extract (GSE) and PVA. Active films
from apple pomace and PVA for antibacterial activities during food packaging
applications have been discovered in recent hybrid study [90, 91].
Halloysite nanotube (HNT) is a non-toxic material used largely for medicine
delivery in medical applications and food packaging. As a result, HNTs were used in
this study as natural reinforcement for a feasible poly(vinyl alchol)/starch/glycerol/
Halloysite nanotube, (PVA/ST/GL/HNT) nanocomposite film to enhance its water
resistance and water contact angle, as well as its mechanical and thermal behavior,
serving as a novel application for food packaging in the industries [92].
Although PVA hydrogels have been the most extensively studied biomaterials
for articular cartilage replacement due to their biocompatibility, permeability, load-
bearing characteristics, and ease of preparation, it has been discovered that they lack
the surface lubrication and biomechanical strength that natural cartilage requires.
The use of doxorubicin-encapsulated hydroxyapatite-polyvinyl alcohol (DOX-HAp-
PVA) nanocomposite for osteosarcoma-affected bone tissue healing has been dem-
onstrated in the recent study [93, 94]. In recent years, PVA or its extracts hydrogel
microparticles and NPs have been reported for a variety of drug carriers, includ-
ing PVA NPs encapsulated by poly(lactide-co-glycolic acid) (PLGA) microparticles
and paclitaxel-loaded PVA-g-PLGA NPs for the treatment of restenosis, as well as
DNA nanocarriers obtained by a modified solvent displacement method. Since the
late 1990s, PVA in the form of hydrogel NPs has been employed for protein/peptide
medication delivery [95]. The novelty production of a homogeneous microstruc-
tured HAp/PVAP nanocomposite might have applications in bone implantation [96].

Polycaprolactone (PCL)

PCL is a biodegradable semicrystalline aliphatic polyester with a melting point


of approximately 60 degrees Celsius and a glass transition temperature of around
60 degrees Celsius. In physiological settings (such as the human body), PCL is
destroyed by hydrolysis of its ester bonds, and as a result, it has attracted a lot of
interest for usage as an embedded biomaterial [97]. The structure of PCL and its
monomer unit is given in Fig. 19.
It has been proved that the first synthesis of PCL by thermal treatment of
ε-caprolactone. Despite several studies focusing on the radical ring opening

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7278 Polymer Bulletin (2023) 80:7247–7312

(A) (B)
Fig. 19  Chemical structure of A PCL and B PCL monomer unit

polymerization (RROP) of 2-methylene-1,3-dioxepane (MDO) under various condi-


tions and the condensation of 6-hydroxycaproic acid, PCL is still primarily synthe-
sized by ionic and metal catalyzed ring-opening polymerization (ROP) of the cyclic
monomer ε -caprolactone [98], which is given in Fig. 20.
PCL’s physical, thermal, and mechanical qualities are largely determined by
its molecular weight and degree of crystallinity, which also influence its capacity
to breakdown under physiological circumstances (through hydrolysis of its ester
bonds). PCL is extremely hydrophobic, semicrystalline, highly soluble at ambient
temperature, and easy to process due to its low melting temperature and excellent
mix compatibility, prompting researchers to investigate new uses, mostly in the bio-
medical industry [99]. Because it is versatile for multiple manufacturing techniques,
poly(caprolactone) (PCL) has been an exceptional polymer for use as a biomaterial
in scaffolding for use in tissue engineering as well as bioabsorbable sutures, wound
dressings, and adhesion boundaries among synthetic biodegradable polymers. Scaf-
folding techniques can be characterized as soft or hard tissue applications in the
context of tissue engineering and regeneration. Selection of material and fabrication

Fig. 20  Different synthesis methods of PCL biopolymer

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Polymer Bulletin (2023) 80:7247–7312 7279

process should be examined due to the variations in soft and hard tissues and their
needs. Recent research on the usage of PCL-based scaffolds in tissue engineering
applications are discussed in the next section [100]. The details of applications, ori-
gin of various biopolymers have been discussed in tabular form later (Table 2).

Polylactic acid (PLA, Polylactide)

PLA, a leading contender, is a thermoplastic, high-strength, high-modulus polymer


that may be manufactured from yearly renewable resources to generate a variety of
components for application in industrial packaging or biocompatible/bioabsorbable
medical devices. It can be easily processed into molded pieces, film, or fibers using
ordinary plastic processing equipment [116]. PLA is one of the most promising
biopolymers as a bioabsorbable polymer since the monomers may be made from
non-toxic renewable feedstock and because it is a naturally occurring organic acid.
PLA has stereoisomers such as poly(L-lactide) (PLLA), poly(D-lactide) (PDLA),
and poly(DL-lactide) (PDLLA). Lactic acid (2-hydroxypropionic acid, LA), a PLA
component unit, occurs as two enantiomers, L- and D-lactic acid [117]. PLA biopol-
ymer has chiral chemical structure containing asymmetric helical orientation, which
given in Fig. 21.
Lactic acid is produced by fermenting sugars derived from renewable sources
such as sugarcane or maize starch. As a result, PLA is a more environmentally
friendly substance with greater properties for usage in the human body (non-toxic-
ity). PLA is the first commercial polymer made from renewable resources that are
harvested once a year [118].
Poly(lactic acid) is made through a polycondensation process that starts with lac-
tic acid. L-lactide polymerization gives PLLA, whereas D-lactide polymerization
yields PDLA. Except for stereochemistry, PLLA and PDLA exhibit identical charac-
teristics. PLA may also be made with different proportions of L and D lactide. After
the polymerization process, the un-reacted monomer must be removed by washing
with ethanol, since the remaining monomer in the polymeric matrix might func-
tion as a plasticizer, lowering the mechanical strength and thermal stability of PLA
[119]. The PLA synthesis reaction is depicted in the diagram below (Fig. 22).
PLA/CS-based copolymers have a higher material potency and a longer time
to degrade. In vivo tests show that PLA strength is sufficient for 8–12 weeks after
implantation. PLA may be useful for internal bone fixation, according to these data.
PLA has also been shown to retain a high level of infertility, which aids in infection
prevention. To promote cell proliferation, orthopedic implantables made of PLA can
be injected with osteogenic or anabolic bioactive. Biodegradable fixation devices
can help prevent osteopenia from occurring as a result of stress shielding caused by
metallic implants. PLA produced with a L-LA/D-LA ratio of 85/15 was effectively
employed to make screws and fixing plates for fracture fixation. The findings dem-
onstrated that the plates may be used to mend fractures without the requirement for
extra support [120–122].
PLA has the potential to play a substantial role in tissue regeneration. PLA scaf-
folds may carry bioactive medicines that aid wound healing, similar to drug delivery
systems targeting carcinomas. Drug-loaded PLA scaffolds, on the other hand, may

13
Table 2  Targeted biopolymers in advance applications, with their origin and diagrammatic representation of their chemical structure
7280

Sl. No Biopolymers Origin: Sources/synthesis Applications Refs.

13
1 Chitosan Sources: crustacean shells, such as lobsters, crabs, and shrimp, as Biomedical applications, bioplastics, nanocomposites, textile [101]
well as fish scales and a variety of other creatures (insects and industries, packaging of food, fuel cell, Wastewater treatment,
fungi)
2 Gelatin Sources: Pig (porcine skins) and cow bones or beef hides, malian Food industry, crime scenes, fingerprints, gelling agent, cosmet- [102]
skins, biovin hides fishes, salmon, catfish, squid, bigeye snapper, ics (bath salts, shampoos, sunscreens, body lotions, hair spray
cuttlefish, lizardfish, etc. and facial cream), medical industry, pharmaceutical industry,
medicine, wine and beer, controlled drug delivery, wound dress-
ing, etc.
3 Starch Sources: Maize, wheat, rice, potatoes, banana, cassava, etc. Food industry (baked foods, confectioneries, pastas, soups [103]
and sauces, and mayonnaises), medicine, textile, paper, fine
chemicals, petroleum engineering, agriculture, and construction
engineering, physical and chemical modifications, drug delivery
applications, pharmaceuticals industries, etc.
4 Cellulose Sources: Agro-waste, domestic-waste, wood, plant, paper, Bio-fuels, consumables, film-forming agent, thickener, blocker, [104]
bamboo, sugar beet, banana rachis, potato tubers, cotton, fique, sustained-release agent, blending agent and suspending agent,
kapok, agave, jute, kenaf, flax, hemp, vine, sisal, coconut, grass, wound dressing, drug carrier, pharmaceutical applications, food,
wheat, rice and barley, etc. drug delivery, coating of solid dosage, scaffolding, biomedical
implants such as cardiovascular implants, Bone and connective
tissue repair, etc.
5 KGM Source: roots of the elephant yam, bulb of the konjac plant Improve metabolic control, lowering plasma cholesterol in rats, [68]
formation of films and blend membranes, coating and packag-
ing, controlled release matrix, food additives, thermoreversible
gels
6 Lignin Sources: agricultural residues, hemp, cotton, woody biomass, and Pharmaceutical industries, wound dressing, wound healing, medi- [105]
energy crops, jute, wood pulp, etc. cine, photocatalyst, drug delivery, controlling disease, immune
booster, electrospinning, water treatment, power sources,
electrochemical energy materials, synthesis of polymers, dyes,
adhesives and fertilizers 3-D printing- plastic composite, etc.
Polymer Bulletin (2023) 80:7247–7312
Table 2  (continued)
Sl. No Biopolymers Origin: Sources/synthesis Applications Refs.

7 Agar Sources: Found in the cell walls of certain species of red algae Antibiotic selection, culture and detection of pathogens from con- [106]
such as Gracilaria and Gelidium taminated food and water, bimolecular separation and purifica-
tion, gel electrophoresis, gel bead chromatography, drug release,
tissue engineering, drug delivery, vaginal capsules, bacteriologi-
cal culture, food industries,
8 PVA Synthesis: Obtained by the polymerization of vinyl acetate mono- Textile, paper industry, and food packaging industry, gene therapy [107, 108]
mers followed by partial hydrolysis
9 PCL Synthesis: Using a catalyst such as stannous octanoate, PCL is Plastics, weather resistance, drug delivery, tissue engineering, [109]
Polymer Bulletin (2023) 80:7247–7312

made via ring-opening polymerization of ℰ-caprolactone additives, food industry, textile industry, chemical factory, steel
manufacturing, automobile industries, paper industries, etc.
10 PLA Source: wheat, straw, corn, and sorghum etc. Tissue engineering, bone re generation, implants, industries, drug [110]
Synthesis: ring opening polymerization of lactate delivery, food industry, medical devices, dialysis, plastics, 3- D
printing, etc.
11 Gallen Gum Source: It naturally occurs on water lilies, secreted by the microor- Thickener, binder, and stabilizer in different food applications, [111]
ganism Sphingomonas elodea, stabilizes the water-based gels, such as desserts and drinking
Synthesis: synthesis chemically by fermenting sugar with a certain jellies, yogurt and sour cream in vegan items, bone repair and
bacterium strain cartilaginous tissue regeneration
12 Pullulan Source: Produced aerobically by growing a yeast like fungus Food industry (coating or packaging material of dried foods, [112]
Aureobasidium pullulans including nuts, noodles, confectionaries, vegetables and
meat), binder for (tobacco, seed coatings and plant fertilizers),
adhesives, pharmaceutical industry (tablets, pills, granules),
flocculating agent, rayon industries, paper industries, printing
and writing, photographic, lithographic and electronic applica-
tions , etc.
13 Dextran Synthesis: synthesized by the action of the bacterium Leuconostoc Anticoagulant, treatment against shocks, surgery, trauma, burn, [113]
mesenteroides drug, etc
7281

13
Table 2  (continued)
7282

Sl. No Biopolymers Origin: Sources/synthesis Applications Refs.

13
14 Curdlan Source: Produced by bacteria, such as Alcaligenes spp., Agrobac- Food (pasta, canned meat) and Dairy products, Therapeutic [114]
terium spp., Paenibacillus spp., Rhizobium spp., Saccharomyces products, Adjuvant, Antioxidant and anti-inflammation agent,
cerevisiae, Candida spp., and fungal sources like Aureobasidium Protection against hyperglycemia, immunomodulation, anti-
pullulan, Poria cocos, etc. Synthesis: Biosynthesis of curdlan allergic activity, etc
from glucose (uridine diphosphate (UDP)- glucose as primary
precursor in the presence of enzyme UDP-glucose pyrophos-
phorylase)
15 Scleroglucan Sources: Produced by various filamentous fungi especially of Oil industry for thickening, discharge of drilling mud’s and [115]
the genus Sclerotium, belonging to the phylum basidiomycota. enhanced oil recovery, construction engineering, adhesives,
Industrially it obtained from, S. rolfsii and Sclerotium glucani- water colors, printing inks and liquid animal feed composition,
cum, Schizophyllum commune, Botrytis cinerea, and Epicoccum thickener in paintings, stabilizer in fire drencher foams and in
nigrum pesticides used in agriculture, food industry (stabilization of
dressings and ice creams), cosmetics, creams and protective
lotions, pharmaceutical products, drug delivery, antitumor, anti-
viral and antimicrobial compound, immune-stimulator , etc
Polymer Bulletin (2023) 80:7247–7312
Polymer Bulletin (2023) 80:7247–7312 7283

Fig. 21  Chiral structure of PLA biopolymer

Fig. 22  Synthetic route of PLA biopolymer

be limited owing to unanticipated changes in the scaffold’s and/or pharmaceuticals’


characteristics during the synthesis method. The PLA/PEG-based porous matrix
films for the delivery of gentamicin sulfate or metronidazole for wound dressing
treatment have been described in recent studies [123]. PLA-based drug delivery sys-
tems have showed potential in cancer therapy therapeutic methods. PLA scaffolds
offer a particularly desirable property for drug delivery systems: long-term drug
release, thanks to their adjustable breakdown rate. In cervical cancer mice models
and in vitro studies, PLA stereo complexes demonstrated drug transport potential.
Improved tumor cell absorption of anti-tumor drugs is aided by sustained doxo-
rubicin release. As a consequence, as compared to non-loaded drug performance,
tumor cell activity was reduced using the drug delivery mechanism. Doxorubicin-
loaded stereocomplex micelles also showed increased tumor prevention rates [124].
Modern technical breakthroughs have broadened the scope of critical care equip-
ment uses. In response to the COVID-19 outbreak, 3D printing has been used to
manufacture ventilators that can handle many patients. Novel studies described a
3D-printed circuit splitter that allowed two patients to be ventilated using a single
ventilator [125, 126].

Gellan gum

Gellan gum is a water-soluble negatively charged polysaccharide generated by Pseu-


domonas elodea. It is generally made up of a tetrasaccharide, which is made up of
two D-glucose residues and one each of D-glucuronic acid and L-rhamnose resi-
dues. One of the most costly hydrocolloids is gellan gum in the market [127].
Gellan is a linear anionic heteropolysaccharide with a straight chain made up
of 1.5:1:1 molecular ratios of the building ingredients d-glucose, l-rhamnose, and

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7284 Polymer Bulletin (2023) 80:7247–7312

d-glucuronic acid. The chain is made up of a tetrasaccharide repeat unit that is


joined together by β-(14)-linked glucose, glucuronic acid, glucose, and rhamnose
in α-(13) linkage given in Fig. 23. The natural product is partly esterified, with
a C2-linked l-glycerate and roughly 50% C6-linked acetate substituents in the
(13)-linked glucose residue. Two acyl substituents—acetate and glycerate—are
present in its natural or high-acyl form. Both residues are found on the same glu-
cose residue, with one glycerate and one acetate for every two repeating units on
average. After heating and cooling, the molecule is anticipated to acquire a two-
or triple helical form, according to X-ray diffraction investigations [128].
Gellan gum is a non-cytotoxic substance that may be injected into tissues.
It has been employed as an eye medication delivery vehicle in humans in vivo
[13]. Gellan is a gelling agent that is widely used. It may, however, be utilized to
make structured liquids that are very effective suspending agents. These struc-
tured liquids are gelling systems that were sheared during or after the gel for-
mation [129]. In comparison with other polysaccharide hydrogels (carrageenan,
alginate, and agar), gellan gum hydrogel is less pH dependent. As a result, gellan
gum is widely employed in the medical and food industries. Despite the fact that
gellan gum hydrogel has good gelation and mechanical properties, there are few
reports of gellan gum hydrogel 3D printing [130]. Ionically cross-linking gelation
through trivalent aluminum cations and covalent cross-linking have been used to
create a new type of glipizide-loaded acetylated gellan gum hydrogel network-
ing beads in recent study (using glutaraldehyde). Spherically shaped trivalent
aluminum cation-induced gellan gum beads were shrunk with distinctive wrin-
kles on the filament surface after treatment with glutaraldehyde for drug delivery
techniques [131]. Despite having unique features that make it ideal for producing
wound healing dressings, gellan gum remains an underutilized polysaccharide.
Gellan is also endotoxin-free when purchased commercially and has been found
to be a viable material for tissue engineering. Gellan gum has also been studied
for use in the administration of antimicrobial medications to wounds and as a
non-toxic tissue engineering scaffold. As a result, gellan gum has the potential to
be used as a multipurpose dressing that can be used as an in situ gelling liquid or
a hydrogel sheet. Despite the fact that gellan gum is an appealing wound healing
source material, there are limited published data on its effectiveness in vivo [132,
133].

Fig. 23  Chemical structure of Gellan Gum

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Pullulan

Pullulan is a microbial polymer generated in the extracellular matrix of Aureoba-


sidium pullulans, a polymorphic fungus. It is a linear homopolysaccharide made
up of repeated units of maltotriose and maltotetraose linked by α-(1,6) and α-(1,4)
linkages. Although pullulan’s chemical composition is mostly made up of repeating
maltotriose units, maltotetraose repeating units can make up to 7% of the overall
length. Regular changes in the α-(1, 6) and α-(1, 4) bond geometry result in impor-
tant features including structural flexibility and high solubility [134, 135].
Pullulan is a non-hygroscopic polymer that is soluble in water but not in organic
solvents [except DMSO]. It is also esculent, non-toxic, and non-carcinogenic, with a
decreased viscosity in aqueous solutions. Pullulan’s repeated linking pattern [α-(1,6)
and α-(1,4)] gives thermal stability up to 250 degrees Celsius. It possesses a number
of distinguishing characteristics, including fiber formation, adhesiveness, and bio-
degradable film formation. As a result, pullulan is used as a blood plasma replace-
ment, as well as a culinary, beauty products, and medicinal ingredient [136, 137].
The chemical structure of pullulan is given in Fig. 24.
Pullulan solutions aid in the maintenance of normal colloid-osmotic pressure in
the blood and tissues, as well as the extension of plasma supply. It functions as a
plasma extender, providing the required therapeutic impact while avoiding unwanted
side effects. Pullulan, when mixed to antigens or viruses as a carrier, makes it easier
to inject antigens or viruses into animals, resulting in antibodies or antiviral vac-
cinations. Pullulan gels can be used to purify enzymes chromatographically or as a
support for enzyme immobilizations [138]. Pullulan bioconjugates can be deployed
to target tumors and deliver genes or drugs. Pullulan-containing hydrogels can help
with wound healing, function as molecular chaperones, and minimize phototoxicity.

Fig. 24  Chemical structure of pullulan, bears α-(1, 4) linkage and α-(1, 6) linkage

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7286 Polymer Bulletin (2023) 80:7247–7312

Pullulan and its derivatives, like other polysaccharides, can be utilized to improve
the biocompatibility of different nanoparticles as well as their colloidal stability
[139, 140].
When compared to direct application on the food surface, the benefit of integrat-
ing antimicrobials into pullulan films is the control and gradual release of the com-
pounds over time. There are three benefits to employing pullulan packaging films
as an antibacterial delivery technique for meat and poultry products. When antimi-
crobials are included into pullulan films and coatings, less antimicrobial is required
to inhibit microorganisms on food surfaces. Furthermore, antimicrobial-containing
pullulan films exhibited long-term inhibitory efficacy and allowed for regulated anti-
microbial component transfer from the film to the food product [141].

Dextran

Dextran is a hydrophilic polysaccharide made up of D-glucopyranose with α-1,6


linkage shown in Fig. 25. Dextran is made from sucrose and maltodextrins, respec-
tively, using dextransucrase and dextrinase enzymes. Dextran may be broken down
using dextranase, which can be found in mammalian tissue [142]. Dextran is a
non-toxic, biocompatible polysaccharide extensively utilized in pharmaceutical
and biological applications [143]. Dextran has been extensively employed in organ
transplantation to minimize inflammatory responses, circulatory thrombosis, and
ischemia reperfusion damage as a reactive oxygen species scavenger and excess
platelet activation reduction. Dextran can be utilized as a blood supplement in emer-
gency situations, according to reports. Dextran has also been utilized as a coating on
substrates to increase their biocompatibility [144, 145]. The chemical structure of
dextran is given in Fig. 25.
Dextran appears to have antithrombotic effects as well as the ability to build
scaffolds that prevent protein and cell adhesion. Dextran-based scaffolds have been
examined for use as coatings for brain implants because of this. Dextran has been
used as a biomaterial in several biomedical research because it is biocompatible,
biodegradable, and accessible in a variety of molecular weights, as well as being
easily derivatized [146].

Fig. 25  Chemical structure of dextran

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Polymer Bulletin (2023) 80:7247–7312 7287

In the field of tissue engineering, a novel conductive interpenetrating poly-


mer network (IPN), preparations of hydrogel composed of polyaniline-grafted
gelatin, carboxymethyl CH, and oxidized promotes, conductive hydrogels have
gained considerable attention, combining conductivity properties with the abil-
ity to form a three-dimensional network. Cell attachment, proliferation, and
differentiation can all be aided by these hydrogels. The amino groups of modi-
fied gelatin were connected with carboxymethyl CH using oxidized dextran as a
cross-linker in that study [147].
Dextran-modified liposomes have been studied for a range of biological appli-
cations, including improved thrombolysis, vascular targeting, and the formation of
pH-sensitive liposomes. Liposomes were enhanced using a pH-sensitive dextran
derivative containing 3-methylglutarylated residues as an efficient antigen-deliv-
ery method. They were able to successfully transfer antigen into the cytoplasm of
dendritic cells (DCs). The formulation increased the induction of antigen-specific
humoral and cellular immune responses in mice when given subcutaneously. Also,
Human endothelial cells were targeted using liposomes modified with functional-
ized dextran [155]. The details of chemical modifications of some specific biopoly-
mers along with modified skeletal structures have been given in tabular form dis-
cussed later in Table 3.

Curdlan

Curdlan is a bacterial polysaccharide produced by Alcaligenes faecalis fermenta-


tion, and its linear structure is made up completely of 1,3-β glucosidic links found
throughout nature shown in Fig. 26. Curdlan has lately gotten a lot of interest
because of its remarkable gelling qualities, which include the capacity to form either
a thermo-reversible or thermo-irreversible gel and powerful physiological functions
including anti-tumor and anti-HIV activity [156].
Alkali-soluble curdlan biopolymer, microbial nutrition, and acid-producing alka-
liphilic bacteria were combined together and injected into Berea Sandstone cores
[157]. Due to their intrinsic biological activity and capacity to form polymeric matri-
ces, sulfated curdlan has medicinal uses as an antiviral and anticancer drug [158].
The anticancer effects of MGlu-curdlan-modified liposomes were greater than those
of dextran derivative-modified liposomes. Furthermore, even in the absence of a tra-
ditional lipid adjuvant (MPLA), MGlu-curdlan-modified liposomes generated robust
antitumor immunity, that may be due to MGlu-strong curdlan’s adjuvant function
and MGlu-curdlan-modified liposomes’ excellent intracellular delivery capability
[159, 160].

Scleroglucan

Scleroglucan is a neutral polymer generated by aerobic fermentation by the fun-


gus Sclerotium rolfsii. Scleroglucan is a branched neutral homopolysaccharide
composed of a linear (1–3)-linked β-D-glucan main chain with (1–6)-linked β-D-
glucopyranosyl groups connected to every third residue. Scleroglucan produces by

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7288 Polymer Bulletin (2023) 80:7247–7312

Table 3  Recent chemical modification of some specific biopolymers with specific reagents and their
modified structures
SI No Biopolymer Modifying agent Modified biopolymer Refs

1 [148]

2 [148]

4 [149]

5 [150]

6 [151]

7 [152]

8 [153]

9 [154]

Fig. 26  Structure of biopolymer curdlan

the fungus that forms linear rod-like triple helices that are kept together by intermo-
lecular hydrogen bonds [161]. The chemical structure of scleroglucan is represented
in Fig. 27.

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Polymer Bulletin (2023) 80:7247–7312 7289

Fig. 27  Structure of scleroglucan

Scleroglucan has a variety of industrial uses, but it was first utilized in the oil
sector for thickening, discharge of drilling muds, and increased oil recovery, where
it outperformed xanthan and other polymers in terms of efficiency and durabil-
ity. In building engineering, scleroglucan and other pseudoplastic biopolymers are
used. Adhesives, water colors, printing inks, and liquid animal feed formulation are
among the other industrial applications. Scleroglucan would be ideal for the stability
of sauces and ice creams in the food business. However, food safety law in Europe
and the USA has yet to authorize scleroglucan [115].

Characterization of biopolymers

The capacity to correctly assess and validate the structures and purity of biopoly-
mers is provided through characterization. When novel materials are being synthe-
sized, a competitor product is being analyzed, or a product’s performance has to be
enhanced, biopolymer characterization is critical. The molecular weight distribu-
tion, molecular structure, shape of biopolymers, thermal characteristics, mechanical
properties, and any additions are all part of polymer characterization. Microscopy
methods, FTIR spectroscopy, NMR spectroscopy, and XRD are all covered in the
physicochemical characterization section. Physical characterizations of biopolymer
membranes and films, such as swelling, degradation/erosion degree, and Porosity
measurements, are then explained. Finally, the primary biological characterizations,
such as cytotoxicity and antimicrobial research, are presented.

Physicochemical characterization

Nuclear magnetic resonance (NMR)

For the determination of polymer structures and the presence of functional groups in
polymer chains, NMR is the most sensitive and powerful enabling technology. NMR

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spectroscopy provides information on the number of magnetically different atoms of


the type being researched and is a frequent technique for determining the structure
of a chemical as well as material purity. The sample weight is less than a milligram,
and the substance might be solid or liquid, pure or mixed. In fact, when used in con-
junction with IR spectroscopy, it generally provides enough information to establish
the chemical structure [162, 163].
NMR can be a useful tool for biopolymers. Recent research using ­23Na+ NMR
measurements has been conducted, and they have proven to be significant in
the investigation of anionic biopolymers as blood flow sensors [164]. The use of
NMR to analyze the antibiotic lipopeptide daptomycin in 1,2-dihexanoyl-sn-glyc-
ero-3-phosphocholine micelles was reported in the recent study [165]. Solid-state
NMR is useful for studying the structure and dynamics of insoluble and non-crys-
talline biopolymers, and it’s also useful for probing membrane protein structure and
dynamics in natural lipid membranes, despite its low sensitivity and poor resolution.
Additionally, some approaches, such as magic angle spinning in solid-state NMR
spectroscopy to characterize the structural dynamics of biopolymers at atomic reso-
lution, can be employed to optimize the research [166, 167].

XRD

The XRD method is used to determine if a material is crystalline or amorphous.


It will specify how cementation materials will be quantified. The atomic arrange-
ment, crystallite size, and defects of crystalline materials may all be investigated
via XRD analysis. An X-ray source of Cu Ka radiation (11/4 1.5406 Aͦͦ) is used for
the XRD examination. It will use the Brag Brentano approach to evaluate and iden-
tify unknown crystalline substances [168, 169]. Because each solid substance has
its own X-ray diffraction pattern, this approach may be used to determine the phases
and components present. The XRD approach involves concentrating an X-ray beam
at an initial angle of 2θ on the biopolymer membrane or film and then reading the
intensity of the diffracted ray using specialized detectors. Following the reading, the
incident ray’s angle 2θ is changed for a fresh reading up to a final 2θ value Bragg’s
law governs the diffracted beam by crystalline phases (Eq. 1)
𝜆 = 2d (sin𝜃) (1)
where ’d’ is the crystalline phase separation between atomic planes, ‘λ’ is the inci-
dent radiation wavelength, and ‘θ’ is the angle of incidence with respect to the eval-
uated plane. A copper radiation source (Cu Kα) with a 2 scan range from 5 to 70
degrees (0.20 degrees/min–0.30 degrees/min scanning speed) is often utilized for
biopolymer film examination [170, 171].

SEM

Scanning electron microscope (SEM) is an acronym for scanning electron micros-


copy. The SEM is a microscope that creates images by using electrons rather than
light. The sample picture is created when an electron beam interacts with the atom

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sample, creating various signals that are collected by detectors. Because biopoly-
mers are non-conductive, SEM examination requires the sputtering of a thin coating
of metal [172].
The SEM method is utilized for surface and fracture investigation in biopoly-
mer films and membranes, allowing for the determination of sample structure and
morphology features. The surface of biopolymer films and membranes is gener-
ally smooth and uniform, especially when created using the casting process [173].
Depending on the film preparation technique and/or biopolymer mixing, a porous
structure can be observed by SEM on the surface and fracture analysis in some cir-
cumstances. SEM may be employed as an essential tool to validate the structure of
the sample on silk fibroin/gelatin multilayered films, according to a recent study.
This approach is important because it offers three-dimensional images of the eye’s
interior, which aids knowledge of component components’ surface morphology
[174, 175].

TEM

When an electron beam is conducted through a testing material sample, transmis-


sion electron microscopy (TEM) pictures are acquired from electron interactions
with resources. Because of the 3-D effect, TEM pictures offer more detailed views
of the surface. In compared to SEM photos, the images acquired through TEM anal-
ysis provide a more enlarged perspective of the material TEM gives a more com-
prehensive surface morphology to understand the behavior of the contacts before
and after the interactions due to the magnification and 3-D analysis capabilities. The
thickness of the outer surface of the testing material may also be determined using
TEM images [176, 177].
Microstructural investigation of biopolymer films and membranes not visible by
SEM, such as microporous structures generated in a modified film production pro-
cess, can be done with the TEM method [178]. In biopolymer composites, TEM is
also utilized to investigate nanoreinforcement dispersion [179].

FTIR

Infrared spectrometry is for investigating how matter interacts with light radia-
tion, especially infrared radiation in the electromagnetic spectrum. Chemi-
cal substances and materials can be identified and characterized using infrared
spectroscopy. In biopolymers, FTIR may be utilized to investigate the different
functional groups and interactions. Hydrogen bonding, amide linkage, and other
interactions may be easily spotted by studying the spectra [180]. Attenuated total
reflection (ATR) sampling device-based Fourier transform infrared (ATR-FTIR)
spectroscopy is one of the methodologies being studied. It needs minimum sam-
ple preparation, allows for simultaneous estimation in both lab and field settings,
and is simple to use. Variable-temperature Fourier transform infrared (FTIR)
absorption spectroscopy was used to explore the thermotropic phase behavior of
a group of recently created self-forming synthetic biopolymers [181]. The FTIR
method has been extensively utilized to investigate the physical and mechanical

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Fig. 28  Physicochemical characterization of biopolymers

Fig. 29  Physical characterization of biopolymers

characteristics of biopolymers in a number of research. The ATR spectral inten-


sity changes of immature and mature cotton fibers were studied using two-
dimensional (2D) correlation mapping [182]. The interactions between several
biopolymers in its composite materials may also be verified via FTIR measure-
ment [183]. The vibrational ranges of biopolymers were used to identify the
specific functional group of the biopolymers, such as ketones, R-CO-R, which
absorb at 1730–1740 ­cm−1. R-COOH carboxylic acids have two distinct bands at
1700 ­cm−1 and about 3500 ­cm−1 that correspond to the C=O and O–H stretching
vibrations of the carboxyl group, –COOH. Carboxylic salts or metal carboxylates
absorb at 1550–1610 ­cm−1, while saturated/aromatic carboxylic acids absorb at
1680–1690 ­cm−1 [184]. Although different characterizations of biopolymers can
be presented pictorically as in Figs. 28, 29, 30.

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Fig. 30  Biological characterization of biopolymers

Physical characterizations

Swelling degree

Polymer swelling is a mass transfer process caused by fluid diffusion into the sub-
stance. The tendency of polymeric systems to absorb the solution of interest, quanti-
fied in mass or volume is termed as swelling degree. Polymer swelling capacity is
determined by the nature of the polymer, the solvent/polymer interaction, and the
polymer structure, and it is a quality that has a direct impact on its use. Because of
their natural source and hydrophilicity, most biopolymers are more vulnerable to the
action of water (swelling characteristic) [185].
Swelling degree studies typically include measuring the sample’s initial mass and
the mass after ‘t’ time in contact with the solution of interest. The swelling degree is
expressed as a percentage in Eq. (2):
Wt − W0
Swelling Degree (%) = × 100% (2)
W0

W0 is the initial sample mass and Wt is the sample mass after ‘t’ time.
The swelling degree of biopolymers is a useful parameter for determining mate-
rial behavior after application. Low swelling qualities are required for food packag-
ing applications, since they provide better barrier features [186]. Swelling behavior
is an important feature in rehydration and exudates absorption for wound-healing
applications. For the optimum wound-healing environment, enough moisture must
be given to prevent dehydration, bacterial development, and infection [187, 188].

Degradation

The focus of biopolymer degradability research is on unwanted behavior or property


loss upon application. The word ‘degradability’ relates to the capability of a poly-
mer to deteriorate during or shortly after application. Photodegradation, mechani-
cal degradation, thermal degradation, and chemical degradation are all examples
of biopolymer degradation. Photodegradation is the degradation of polymer chains

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caused by ultraviolet (UV) light and radiation; mechanical degradation is the effect
of mechanical forces on polymer stability; thermal degradation is the degradation of
the polymer caused by temperature changes; and chemical degradation is the degra-
dation of the polymer caused by hydrolysis, enzymatic degradation, or pH change
[189].
Sample mass loss and mechanical property loss are the most typical criteria used
to assess biopolymer degradation. Degradation degree by sample mass is calculated
by Eq. (3)
Wi − Wt
Degradation(%) = × 100% (3)
Wi

where Wi and Wt are the dry weight of the sample with respect to time ‘t.’
The degradation degree is computed by measuring the mass or mechanical char-
acteristics of a sample in a simulated application environment (simulating chemi-
cal composition, pH, and temperature). Microscopy (in general, SEM method) may
also be used to see biopolymer erosion since deterioration destroys the biopolymer
structure. For a wide range of applications, determining the degree of degradation/
erosion of biopolymer membranes and films is critical. Degradation can be a goal
attribute depending on the application, for as in biodegradable bags and skin tissue
engineering [190–192].

Porosity measurements

Porosity measurement is a physical characterization method for determining the


capacity of polymer film membranes to absorb water. The procedure entails A little
piece of uniformly sized pre-weighed polymer films was submerged in the solution
like alcohol. The film fragments are removed after a few minutes, and the ultimate
weight is calculated.
The porosity of the polymeric film membrane can be calculated by using math-
ematical formula is given below in Eq. 4

(4)
( ) ( )
Porosity (P) = W2 − W1 ∕ 𝜌V1

where W1 and W2 are the weight of the film before and after immersing in the
alcohol solution, respectively. V1 is the volume of the solution taken before the
immersing the film and ρ is the density of the solution.

Biological characterization

Cytotoxicity

Nowadays, most tests are carried out in vitro, in accordance with international rec-
ommendations to reduce in vivo testing. To evaluate the effect induced by the bio-
material’s exposure to the cells, the first three biocompatibility tests can be done
using cell cultures, either primary or cell lines. The cytotoxicity test, which is done

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on all biomaterials, employs BALB/c 3T3 mouse fibroblasts or normal human


epidermal keratinocytes as the cytotoxicity endpoint and neutral red uptake as
the cytotoxicity endpoint. Other vital dyes, such as 3-(4,5-dimethyl-2-thiazolyl)-
2,5-diphenyl-2H-tetrazolium bromide (MTT) or 3-(4,5-dimethyl-2-thiazolyl)-5-(3-
carboximetoxiphenyl)-2-(4-sulfophenyl)-2H-tetrazolium bromide (MTT), might be
used [193]. The toxicological endpoint linked with substances that have the inher-
ent capacity to produce skin sensitivity is known as sensitization. An overreaction
of the adaptive immune system causes this negative consequence. Sensitization
was induced on the initial touch with allergy symptoms, and subsequent interaction
resulted in sensitization [194, 195].

Antimicrobial activity

In terms of antimicrobial activity, the biostatic or biocide microbiological charac-


teristics of films in solid or liquid media may be determined. The procedure used
will be determined by the qualities of the film as well as the microorganism to be
utilized. The Clinical and Laboratory Standards Institute standards for macrodilu-
tion and microdilution in broth might be used to test antimicrobial activity. Employ-
ing bigger volumes and, as a result, more samples, macrodilution is used. In both
situations, the microorganism was put in varied quantities to the tubes (macrodilu-
tion) or 96 microplate wells (microdilution), and the films were added in proportion.
There were both positive and negative controls. Using pure medium as a control,
the final concentration was determined as the minimum concentration that resulted
in no observable bacterium development after 24 h of incubation at 37 °C, depend-
ing on the studied microorganism. The biostatic level was evaluated by plating a
100 L solution from the test tubes onto agar plates without obvious bacteria growth
and incubated for further 24 h at 37 °C. The films are regarded biostatic if there is
growth, but they are also considered biocides if there is no growth [196, 197].

Applications of biopolymers

Water treatment

Novel approaches for water purification have been developed by researchers. Water
recycling solutions that include green water treatment are also being researched.
Due to the remarkable qualities of biopolymers, using natural polymers in mem-
brane synthesis, manufacturing, and production to create entirely biodegradable
membrane materials becomes perfect and appealing [198]. The adsorption–desorp-
tion process has recently been utilized to remove chlorophenoxyacetic acid herbi-
cides from water using orange peel-activated carbon. As a result, chlorophenoxy-
acetic acid herbicides were considerably absorbed from water by this bio-sourced
activated carbon. Membranes may be adjusted using these biopolymers. Because of
their abundance of polysaccharides, cellulose polymers have been widely used in
water applications [199]. Membranes made from carboxymethyl cellulose (CMC),
cellulose nanofibrils (CNF), and bacterial cellulose (BC) modified cellulose with

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various functions. As a result, the azo and anthraquinone dyes were effectively
removed from wastewater using these modified membranes [200].
The electrospun cellulose acetate nanofibrous membrane may filter out chro-
mium, metal ions, and hazardous organic compounds in addition to microorganisms.
For the removal of lead from contaminated water, magnetic nanoparticles immobi-
lized on cellulose acetate nanofibrous membranes were created [201]. The densely
interconnected porous cellulose acetate nanofibers membrane with homogenous dis-
tribution over the polymer bodies has been discovered to have a unique use in water
filtering. The cellulose acetate nanofibrous membrane has an average fiber diam-
eter of 30–110 nm. As a result, the electrospun cellulose acetate membrane contains
homogeneous, continuous, smooth, and interconnected porous nanosized fibers,
which are mostly used to filter microorganisms in water [202].
Biopolymer-based flocculants have the promise to be scaled up for commercial
use. A triangle assessment model was designed to evaluate the effectiveness of
biopolymer-based flocculants in wastewater treatment in terms of economic sustain-
ability [203]. Chemical flocculants such as polyaluminum chloride (PAC) were uti-
lized in the removal of chemical oxygen demand (COD), suspended solids (SS), and
aluminum ­(Al3+) from unclean water during water treatment. CS composite floccu-
lants produced utilizing a mixture of CS, polyaluminum chloride, and silicate were
shown to be more effective in eliminating contaminants than standard flocculants
[204]. Tanfloc, a natural polymer derived from Black acacia, was compared to the
commercial synthetic polymers Flopam and Zetag for flocculation of microalgae,
Nannochloropsis oculata, and Chlorella vulgaris. Both commercial and biopolymers
effectively treated both fresh and marine water, showing that Tanfloc, a natural poly-
mer, can be used as a promising polymer due to its cheap cost and environmentally
benign properties [205].

Tissue engineering applications

Chitosan has a number of intriguing features, including the ability to form a gel,
increased adsorption capacity, superior biodegradability, exceptionally high biocom-
patibility, and non-cytotoxicity, as well as enhanced biological qualities including
antifungal, antibacterial, and antitumor activity. Because of its strong cell adhesion,
cell survival, cell interaction, and neurite outgrowth, the hydrogel form of chitosan
is most commonly utilized in tissue engineering. Long-term stability, elasticity, self-
assembly, and biological activity are all characteristics of elastin, a structural pro-
tein. Elastin is a protein that provides elasticity to organs and tissues. It is found
in organs, particularly elastic ligaments, blood vessels, skin, and the lungs, where
elasticity is important. Where the elastic effect in parts of our body, such as skin
and blood vessels, is visible, the insertion of elastin inside biomaterials is extremely
important. As a result, it is more commonly employed for soft tissue regeneration
[206, 207].
In the recent decade, interest in DNA- and RNA-based scaffolds has grown at
an exponential rate. DNA-derived polymers can build nanostructures or tridimen-
sional networks among hybridized DNA or RNA chains, in addition to serving as

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cross-linkers between copolymers, as in DNA-acrylamide hydrogels. When certain


sequences were recognized by the enzymatic complex, DNA-based hydrogels were
used to regulate the mechanical characteristics of the materials. Hydrogels based on
DNA–polyamide (DNA–PA) have improved cellular behavior and may be used for
tissue cultivation in live organisms. The convergence of poly(ethylene glycol) dia-
crylate (PEGDA)/DNA hybrid hydrogels for a cell-free system using a physically
cross-linked DNA network-based cell fishing technique has been described in recent
works. As a consequence, bone marrow mesenchymal stem cells were efficiently
captured via 3D enveloping and enzyme-triggered release [208, 209].

Drug delivery

The qualities of biopolymers and their derivatives were superior in terms of func-
tionality, water solubility, non-toxicity, biodegradability, and biocompatibility. Fur-
thermore, by releasing drugs in a regulated manner, these biopolymers can lessen
medication toxicity. Collagen is the most prevalent protein in the animal kingdom,
consisting of a glycine–proline–hydroxyproline repeating unit in a triple helix shape.
It has been used in drug delivery applications as microparticles, coatings, and films
due to its good biocompatibility [210].
The most ubiquitous biopolymer, cellulose, has outstanding mechanical and
biological features such as biocompatibility, low cytotoxicity and biodegradability.
Microcrystalline cellulose (MCC), cellulose nanomaterials (CNC and CNF), and
bacterial nanocellulose (BNC) are examples of materials with different aspect ratios
that are good prospects for drug delivery systems [211]. Chitosan-drug conjugation
is among the most effective drug delivery methods. Various molecular weights of
chitosan were utilized for conjugation formation, and the cleaving condition might
be pH or GSH (glutathione) sensitive depending on the drug type. For any sensitive
protein or gene delivery, chitosan hydrogel production is another option [212].

Agriculture applications

A variety of natural biopolymers incorporating pesticide active groups have been


commercialized in order to generate suitable controlled release combinations for
fungicides and herbicides. When coupled with one or more fungicides, the gum
biopolymers have a specific use in the defense of seeds against fungal pathogens
[213].
Chitin and CS are naturally occurring chemicals that have the potential to manage
plant diseases in agriculture. They were shown to have antifungal, antiviral, antibac-
terial, and antiparasitic properties. They have also been used to chelate nutrients and
minerals to prevent diseases from gaining access to them, as well as to boost plant
defense [214].
A degradable agricultural mulching film made from a starch-polyvinyl alcohol
film containing up to 40% starch, urea, ammonia, and varying amounts of low-den-
sity polyethylene (LDPE) and poly(ethyleneco-acrylic acid) (EAA) might be cov-
ered with a thin layer of water-resistant biopolymer [215].

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The biopolymeric coating offers various advantages, including the ability to


extend the active ingredient’s action. Because it releases the appropriate quantity of
active agent over a longer period of time, biopolymer coating permits significantly
smaller amounts of effective component to be employed than traditional pesticides
[216].
To allow an initial burst of 2,4-D followed by a regulated bioactive release, the
non-toxic and biodegradable matrices of cellulose derivatives ethylcellulose/hydroxy
propyl methyl cellulose (HPMC), cellulose acetate butyrate butyryle (CAB)/HPMC,
and pure CAB were utilized in microparticles. This method enabled for high herbi-
cide effectiveness to be achieved early on and to be maintained for a long time [217].

Food packaging

polyhydroxyalkanoates (PHAs) are now one of the most abilities of different to fos-
sil-derived polymers in the Bioeconomy, with the greatest potential to replace poly-
olefins in packaging applications, due to their biocompatibility and physical quali-
ties,. Although cellulose acetate’s gas and moisture barrier qualities are not ideal
for food packaging, it is ideal for items that require a lot of moisture since it allows
for breathing and avoids fogging [218, 219]. According to recent study, PE and PP
packaging foils coated with CS and polyphenol colloidal formulations have a lot
of promise as active (antioxidant and antibacterial) packaging in the food business
[220].

Application of biopolymer for energy

Biopolymers are used to study polymer electrolytes. Membranes holding ions dis-
solved in polymer serve as polymer electrolytes. Ionic conduction requires the pres-
ence of electron donor atoms, such as N, O, or S, in the polymer. The dissolved
salt cations have just a weak interaction with these atoms. Conductivity in poly-
mer electrolytes is influenced by both cations and anions. Biopolymers Only two
of the compound’s atoms, O and N, have a lone pair of electrons. Since chitosan’s
backbone comprises hydroxyl, ether (C–O–C) and amine functional groups, it may
be designed to address the needs of a particular application. The presence of polar
functional groups in their structure explains their water-attracting abilities [221].
Dissolving CS in acetic acid produces a membrane layer with extremely low
room temperature conductivity (− ­10−10 to ­10−9 S ­cm−1). It may, however, func-
tion as a matrix for ionic conduction because of its strong film-forming capacity and
ability to solvate numerous inorganic salts. Adding lithium salt or ammonium salt
to chitosan for proton conduction improves the conductivity at room temperature.
An very high conductivity (2.42 ± 0.01) × ­105 (S c­ m−1) was achieved using the phth-
aloylation combination of 70% phthaloyl chitosan–30%NH4SCN (S c­ m−1) [222].
Glucose molecules with three hydroxyl functional groups are bonded to form
the polymer cellulose. It is defined as the average number of substituted hydroxyl
groups per glucose in the specified form of methyl cellulose. Because of the pres-
ence of lone pair electrons on the oxygen atoms in methyl cellulose, these atoms

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may function as complexation sites and interact with salt cations in a weak way.
An electrolyte based on methylcellulose exhibits ionic conductivity when com-
posed of 63.75 weight percent methylcellulose, 21.25 weight percent ­NH4NO3,
and 15 weight percent PEG, as well as 75 weight percent methylcellulose, 25
weight percent ­ NH4NO3 − 1.1 × ­10−4, and 2.10 × ­10−5 (S ­ cm−1), respectively
[223].
Recently, it has been shown that polymer electrolyte membranes are very
efficient and dense in energy. By using biopolymer in polymer electrolyte fuel
cells (Fig. 31), less C­ O2 is released into the atmosphere, which benefits the
environment.
Solid gellan gum (GG) polymer electrolyte for energy use has been shown
in recent study. Solid gel electrolyte synthesis based on carbohydrate polymer
(Phytagel/GG) was established in this work. As a dye-sensitive solar cell mate-
rial, this substance might be used (DSSC) [224].
In chemistry, physics, materials, and microelectronics, biopolymers are
employed in FETs. Material applications expand beyond sophisticated biologi-
cal devices to electrical/electronic materials, making them unique for electronic
switches, storage devices, gates, biosensors, and biologic transistors. Due to
their vast surface area, excellent electrical conductivity, and porous nanostruc-
tures, biopolymers are being employed to produce Supercapacitor (SC) (more ion
adsorption and active sites for the charge transfer reactions). Biopolymer dielec-
trics boost supercapacitor efficiency. Due to their cheap cost and photolytic eco-
friendliness, biopolymers are employed in LED, PV, and photodetector systems
[225].

Fig. 31  Diagram showing polymer electrolyte membrane fuel cell

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Environmental application

Biopolymers are viable alternatives to non-renewable goods because of their biodeg-


radability, environmentally benign production methods, and broad variety of uses.
Since synthetic polymers have harmed our ecosystem, it is clear that any attempt to
get materials from renewable sources that degrade rapidly in the environment is crit-
ical if we are to repair the damage done by their indiscriminate use and avoid further
deterioration. Biopolymers such as lipids, polysaccharides, and proteins, which have
been examined as renewable raw resources and are viewed as a replacement to plas-
tic non-biodegradable and based on petroleum, have been increasingly in demand in
recent decades [226].
The thermoplastic nature of biopolymers means that they have many of the same
qualities as petroleum-based plastics. Unlike synthetic materials, biodegradation by
bacteria, fungus, and algae yields products such as ­CO2, water, and compost. Poly-
hydroxyalkanoates (PHA), a biopolymer generated by microorganisms, has physical
qualities comparable to petroleum-based plastics (e.g., are rigid, brittle or flexible)
[227].
Polyaniline-based titanium dioxide nanocomposite (PANIs/TiO2 NCs) has been
shown to have been blended by hydrothermal and low-temperature thermal treat-
ment processes in recent study. Photocatalytic activity for the liquid-phase break-
down of methyl orange (MO) was shown to be greater in the PANIS/TiO2 NCs when
irradiated with both UV and visible light. An improved sol–gel photocatalytic activ-
ity was used to make the hierarchical 3-D flowerlike T ­ iO2/PANIs NCs, which were
effective in degrading organic contaminants when exposed to visible light. Under
visible-light irradiation, Pei et al. created a synergetic effect of ZnO/PANIs NCs by
chemisorption and a cold plasma treatment approach [228].
To enhance soil properties, biopolymers may be useful because of their biodeg-
radability, which has no detrimental impact on the environment. Also, unlike MICP,
biopolymer treatment may be utilized to enhance soil with a finer particle size distri-
bution. Biopolymers also have an advantage over MICP since they do not need to be
injected with nutrients before they can be utilized to enhance the ground. Research
has shown that biopolymers like Guar Gum (GG), Xanthan Gum (XG), CS, and
Beta 1,3/1,6 Glucan (BG) can significantly enhance the engineering qualities of soil
[229].

Advanced biomedical applications

Biopolymers have a wide range of medical applications, including occlusion, sutur-


ing, covering, fixing, isolation, adhesion, cellular proliferation, controlled drug
delivery, contact inhibition, and tissue guiding. As a result of their outstanding pli-
ability and consistent knot toughness, poly-(L-lactic acid), poly-(glycolic acid), and
copolymers of these two substances are commonly used as sutures. Poly(ortho ester)
and poly-hydroxy groups are often used in medication delivery. In order to create
artificial blood arteries, polyurethanes must have properties like pliability, hardness,

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and resistance to wear and tear [230, 231]. The administration of drug delivery,
the creation of hydrogels, and tissue engineering all benefit from the use of poly-
esteramides. These include surgical masks, gloves, surgical gowns, towels, sanitary
napkins and diapers as well as surgical headgear, panties shielded and antimicro-
bial textiles for surgical curtains and surgical curtains as well as wipes. In surgi-
cal gowns, bio-based PET may be used in lieu of cotton, polyester, and PE [232].
Due to the adaptability of polylactic acid, it may be used to create a wide variety
of items, including but not limited to hats, gowns, and masks. For its remarkable
absorption properties, thermoplastic starch is an essential ingredient in the manu-
facture of diapers for young children. Alginate fibers, catgut, collagen, chitosan, and
superabsorbent polymer are just a few of the biomaterials often used in medical and
hygienic applications [233].

Challenges and future perspectives

In this review, we discussed the potential use of biopolymeric materials in bioen-


gineering applications, which has been expanded by evaluating their physical,
mechanical, degradability, biocompatibility, etc. qualities, the most promising prov-
ince technologies for the synthesis of smart biopolymers, and the varied green uses
in bioengineering.
The most pressing issues for humanity in the future will be energy and resources,
food, health, transportation and infrastructure, and communication. Biopolymers
will be crucial in overcoming these issues. Polymers will be the material of the next
century, and their manufacture will provide global access to the best solutions. Syn-
thetic biopolymers have long been used in medicine. Synthetic polymers are used to
make medical devices and artificial organs. Future pharmacy may also use synthetic
polymers. Polymer science can conserve energy and boost renewables. In the future,
fossil fuels will not meet global energy needs. Fuel cells are intended to help achieve
the aim. Fuel cells may replace batteries and ICE generators. Next, research will be
commercialized. Fuel cells will be a worldwide commodity. Modifying biopolymer
and nanofiller characteristics may increase their use in electrical components.
Biopolymers are expected to rise in value as new solid adaptations are developed
and the cost of manufacturing these bio-plastics continues to decrease. Bio-plastics
may replace conventional plastics in a variety of applications, such as food pack-
aging, plastic plates, mugs, cutlery, and storage packs, and so assist to reduce the
impact on the environment.
Electrical industries have increasingly accepted plastics for plugs, sockets, wire
and cable insulation, and housing electrical and electronic equipment. Major poly-
mer-targeting sectors include ceramics, stem cell biology and regenerative medicine,
packaging, food retorting, automotive, aerospace, and electronics.
According to research, smart packaging may improve the accuracy of predict-
ing the expiration date and time of packaged food and materials. Further study
on biopolymer and filler nanoparticles will provide nutritious packaged food and
increased shelf life for both food and packaging.

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In the future, new biopolymer-based materials with regulated functions will


be developed, allowing for a wider range of biomedical applications. Bioengi-
neering, biochemistry, and molecular biology advancements in recent years have
contributed to enhancing the biological performance of biopolymer-based formu-
lations and new application areas.
Cellulose is a sustainable biomedical material that has encouraged research-
ers to develop innovative cellulose-based products. Cellulosic materials have
good physical and biological characteristics, biocompatibility, biodegradability,
and low cytotoxicity, making them ideal for tissue engineering scaffolds, wound
and burn dressings, medical implants, and drug delivery systems. Surface and/or
bulk changes of cellulose allow for novel functional materials. Modification alters
materials’ physicochemical characteristics, particularly at the nanoscale. Future
studies should examine how foreign molecule inclusion affects nanocellulose’s
cytotoxicity and biocompatibility. The use of organic–inorganic bionanocom-
posite for vaccine administration is a relatively new phenomenon, and the area
has yet to witness substantial advancements. Calcium phosphate, iron oxide, and
layered double hydroxides are some of the nanoparticles that might be useful in
these applications.
This is an exciting new field of study that capitalizes on the synergistic assem-
bly of biopolymers and nanosized solids derived from natural or synthetic organic
and inorganic compounds.

Conclusion

Over the last few decades, there has been a progressive development in industry
interest in biopolymers and biopolymer-based green goods. Biopolymers are renew-
able, non-toxic, environmentally friendly, biodegradable, lightweight, easy to man-
ufacture and have a high skeletal behavior that improves mechanical strength and
stiffness and can be customized to meet a variety of performance needs. Many fac-
tors influence the qualities of hybrid biopolymer-based materials, including chemi-
cal composition, specific temperature, environmental effect, particle size, and sur-
face area. The comprehensive study showed that biopolymers are acceptable with
tissue engineering, drug control, agricultural, pharmaceutical, biomedical, bioengi-
neering, and food sectors, as well as that they have a wide range of uses. Further
research on biopolymer-based products has the potential to replace conventional
harmful non-biodegradable materials in the near future. When these bioproducts
grow more durable and function better, there is the potential for the establishment
of new markets. Continuous research into performance and life-cycle evaluation is
required to determine the biopolymers’ usefulness.

Acknowledgements The authors are grateful to the Council of Scientific and Industrial Research (CSIR),
New Delhi, for providing financial support (Project Grant No. 22(0847)/20/EMR-II, dated: 10.12.2020).
The authors also gratefully acknowledge to National Institute of Technology (NIT), Arunachal Pradesh,
India, for assistance and support.

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