Latest Biomaterials and

Tec h n o l o g y i n D e n t i s t r y
Roya Zandparsa, DDS, MSc, DMD

KEYWORDS
 Dental  Biomaterials  Technology  Implant  Navigation  Laser
 Nanotechnology  Tissue engineering

KEY POINTS
 In oral and maxillofacial surgery, navigation technology is applied with particular success
in arthroscopy of the temporomandibular joint, in the surgical treatment of posttraumatic
deformities of the zygomatic bone, in orthognathic surgery, and for distractions, osteoto-
mies, tumor surgery, punctures, biopsies, and removal of foreign bodies.
 The use of laser beams for caries removal allows the preservation of the natural shape of
decayed cavities without the need for preventive extension of prepared cavities.
 With nanodentistry, it is possible to maintain comprehensive oral health care by involving
the use of nanomaterials, biotechnology, and ultimately dental nanorobotics. Nanorobots
induce oral analgesia, desensitize teeth, manipulate the tissue to realign and straighten an
irregular set of teeth, and improve the durability of teeth. They can also be used for
preventive, restorative, and curative procedures.
 Strategies to engineer tissue can be categorized into 3 major classes: conductive, induc-
tive, and cell transplantation approaches.
 Several populations of cells with stem cell properties have been isolated from different
parts of the tooth. These populations include cells from the pulp of both exfoliated (chil-
dren’s) and adult teeth, from the periodontal ligament that links the tooth root with the
bone, from the tips of developing roots, and from the tissue (dental follicle) that surrounds
the unerupted tooth.

Replacement of missing tooth structure has been challenging. A long-term goal of

dentistry was the ability to anchor a foreign material into the jaw to replace a tooth.1,2

DENTAL IMPLANTS

It is thought that the history of dental implants dates back to the ancient Egyptians
around 3000 BC, because they used to hammer trimmed seashells into the jaw to
replace missing teeth. Dental implants require the optimization of several important
variables to enhance the chances of success, including appropriate material selection

Tufts University School of Dentistry, Postgraduate Prosthodontics Division, 1 Kneeland Street,

Boston, MA 02111, USA
E-mail address: [email protected]

Dent Clin N Am 58 (2014) 113–134

http://dx.doi.org/10.1016/j.cden.2013.09.011 dental.theclinics.com
0011-8532/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
114 Zandparsa

and design; an understanding and evaluation of the biological interaction at the inter-
face between the implant and the tissue; careful and controlled surgical techniques;
collaboration between various specialties to optimize patient selection; selection of
appropriate implant design, size, and surface; and long-term follow-up care.1,3
There have been 3 basic designs of dental implants. The endosseous implant was
preceded by the subperiosteal and transosteal implants. The most successful and
frequently used implant design is the endosseous type. Dental implants have been
made from many different materials, such as platinum, silver, steel, cobalt alloys, tita-
nium and alloy, acrylic, carbon, sapphire, alumina, tantalum, niobium, zirconia, and
calcium phosphate compounds.4–8 An implant is placed in a surgically prepared
osteotomy, submerged and integrated within the bone of the mandible or maxilla.
Success of endosseous dental implants depends on the formation of the biologic
interface between the bone and the implant, which is formed by the growth of new
bone. This interface, osseointegration, represents integration of the new bone along
the implant surface.

CERAMICS

Ceramics have been used for manufacture of dental implants based on the properties
of biocompatibility and inert behavior.3 Because bone is composed of a calcium phos-
phate ceramic, hydroxyapatite, bone replacement using a substance of similar
composition, such as synthetic hydroxyapatite, could be presumed to be suitable. Ce-
ramics are mixtures of nonmetals and metals and can be divided into metallic oxides
or other compounds. Ceramics have been used in manufacture of dental implants
because of their high strength, suitable color, and low thermal and electrical conduc-
tivity. Nevertheless, the limitation of this type of material is based on low ductility and
brittleness.7 These properties have led to the development of metallic implants, which
may be designed with calcium phosphate coatings.1,2
Metallic oxides (eg, Al2O3, ZrO2, TiO2) have been used for root form, endosteal plate
form, and pin-type dental implants. Calcium phosphate (CaPO4), also known as cal-
cium phosphate ceramics, has been used in dental reconstructive surgery, endosteal
implants, and subperiosteal implants as a coating for stronger implant materials.7,9

Zirconia Implants
The first ceramic implant placed in United States and Germany was used as a medical
joint substitute in the 1970s.9 Various zirconia dental implant systems are available
commercially as well as the use of zirconia particles comprising a coating material.
Many studies have shown enhanced implant osseointegration in titanium implant sur-
faces coated with zirconia and that zirconia implants are capable of contributing to
similar bone-implant contact to that of titanium implants.10–12
Yttria stabilized zirconia (Y-TZP) is currently considered an attractive and advanta-
geous endosseous dental implant material because it presents enhanced biocompat-
ibility, improved mechanical properties, high radiopacity, and easy handling during
abutment preparation.13 Zirconia ceramic is well tolerated by bone and soft tissues
and possesses mechanical stability.14 Because the difference in bone-to-implant
attachment strength between bioinert ceramics and stainless steel is not significant,
the affinity of bone to bioinert ceramics has almost the same capacity as metal al-
loys.14 This fact was confirmed in another in vivo study, in which no differences in
soft tissue health were seen in peri-implant mucosa adjacent to zirconia and titanium
abutment surfaces.15 From the available data, osseointegration of Y-TZP implants
might be comparable with that of titanium implants.16
 Latest Biomaterials and Technology 115

Regarding the impact of the design (1 piece vs 2 piece) on the biomechanical

behavior of Y-TZP implants using chewing simulation testing conditions, a prototype
2-piece zirconia implant revealed low fracture resistance at the level of the implant
head and therefore questionable clinical performance, whereas 1-piece zirconia im-
plants seem to be clinically applicable. Moreover, it preparation of 1-piece zirconia
implant to accept a crown had a statistically significant negative influence on the
implant fracture strength.14 Pirker and Kocher placed an immediate zirconia implant
in the maxillary first premolar region and evaluated the clinical outcome of this implant.
After a 2-year follow-up, a stable implant and unchanged peri-implant marginal bone
level was observed.17 Lambrich and Iglhaut18 compared the survival rates for zirconia
(Z-systems) and titanium dental implants. Zirconia implants had a comparable survival
rate with titanium as long as there was a high primary stability and load-free healing,
ideally under complete tooth-supported protective stents. Kohal and colleagues19
found that yttrium-partially stabilized zirconia (YPSZ) implants had a similar stress
distribution to commercially pure Ti implants and presented a pattern of low, well-
distributed stress along the implant-to-bone interface. Kohal and colleagues20 evalu-
ated the cyclic loading and preparation on the fracture strength of a zirconia dental
implant system and observed that preparation as well as cyclic loading can decrease
the fracture strength resistance of zirconia implants.

Zirconia Implant Abutments

All-ceramic implant abutments made from aluminum oxide ceramic material (glass
infiltrated or densely sintered alumina) were first introduced as an esthetic alternative
to titanium in the mid-1990s. The alumina abutments presented pleasing optical prop-
erties, adequate fracture strength for the anterior regions, and excellent 5-year prog-
nosis. Implant manufacturers are also producing abutments made from zirconia.
Besides strength considerations, Y-TZP implant abutments offer enhanced biocom-
patibility, metal-like radiopacity for better radiographic evaluation, and ultimately
reduced bacterial adhesion, plaque accumulation, and inflammation risk. Moreover,
Y-TZP abutments may promote soft tissue integration, whereas favorable peri-
implant soft tissues may be clinically achieved adjacent to zirconia or alumina-
zirconia abutments and zirconia healing caps.2 Zirconia abutments are successors
to the densely sintered high-purity alumina (Al2O3) abutments. Zirconia abutments
are radiopaque and show significantly higher resistance to fracturing.21
Zirconia abutments are available in prefabricated or customized forms and can be
prepared in the dental laboratory either by the technician or by using computer-aided
design/computer-aided manufacturing (CAM) techniques. The radiopaque esthetic
abutment has good biocompatibility and is designed to engage the implant directly.
They offer sufficient stability to support implant-retained reconstructions, especially
in the incisor and premolar locations. They are indicated in areas with limited gingival
tissue height and also minimize the gray color transmitted through the peri-implant tis-
sues associated with metal components.17,22

COMPUTER-AIDED NAVIGATION IN DENTAL IMPLANTOLOGY

Computer-assisted navigation systems are widespread in neurosurgery; orthopedics;

and ear, nose, and throat surgery.23–26 In oral and maxillofacial surgery, navigation
technology is applied with particular success in arthroscopy of the temporomandib-
ular joint; in the surgical treatment of posttraumatic deformities of the zygomatic
bone; in orthognathic surgery; and for distractions, osteotomies, tumor surgery, punc-
tures, biopsies, and removal of foreign bodies.23
116 Zandparsa

At present, a trend in the use of computer-assisted navigation in dental implantology

can be observed. Navigation systems are developed for research purposes and for
use by commercial companies that provide hardware and software to position dental
implants. A substantial advantage of navigation is precise preoperative planning,
which is optimized by taking into consideration prosthetic and functional aspects.
This advantage is of crucial importance to avoid an unfavorable mechanical load,
which can lead to peri-implant bone loss and thus an early loss of implants.23–27
Furthermore, navigation systems improve intraoperative safety, because damage to
critical anatomic structures such as nerves or neighboring teeth can be avoided.
The accuracy attainable with computer-aided navigation systems has been examined
in several studies and found to be sufficient.23–29
The work flow consists of getting all vital information from the patient’s anatomy
using a computed tomography (CT) scan or a cone-beam scan. The converted scan
data result in three-dimensional representations of the patient’s anatomy and provide
vital information needed to plan the implant placement. The treatment planning results
in creation of a customized drill guide that links the computer-assisted planning to the
surgery and helps the surgeon to place the implants more accurately. The computer-
aided surgical guide indicates the angle, position, and depth of the implants in the pre-
operative plan and can be placed on the bone or on the mucosa to guide the drill in the
planned position during the surgery (Fig. 1).30
At present, three-dimensional CT and cone-beam CT (CBCT) systems allow a more
reliable treatment planning than when only two-dimensional data were available, and
allow the virtual implant planning driven by restorative considerations and the succes-
sive fabrication of surgical guides by means of CAM or rapid prototyping techniques.
The developments in computer-aided planning by means of the use of three-
dimensional virtual models have modified the interventional possibilities in implant

Fig. 1. Navigator system for CT-guided dental implant surgery. (A) The three-dimensional
image is calculated and implants are planned. (B) The relation of the implants to the
bone and the planned restoration. (C) The SurgiGuide with drill guide. (Courtesy of Mate-
rialise Dental Inc, Available at: http://www.materialisedental.com.)
 Latest Biomaterials and Technology 117

dentistry. Multiple appointments are required, beginning with the initial diagnosis,
impressions to fabricate the diagnostic casts, the diagnostic waxing, and fabrication
of the radiographic template.31

CBCT RADIOLOGICAL SYSTEM

CT is routinely used in the diagnosis and treatment planning of dental and maxillofacial
structures, with particular reference to dental implant surgery.32–34 Special application
software allows attainment of two-dimensional images perpendicular to the dental
arch and panoramic views of the dental arch as well as three-dimensional views. How-
ever, the cost and complexity of these machines, along with the problems related to
the high dose absorbed by the patient, limit the use of this modality.
There is a new type of CT machine devoted to the imaging of dental and maxillofa-
cial structures and based on the cone-beam technique (CBCT). The CBCT technique
has been used in radiotherapy, using fluoroscopic systems or modified simulators in
order to obtain cross sections of the patient in the geometric conditions of the treat-
ment.35–40 The CBCT technique has also been used in vascular imaging and in micro-
tomography of small specimens for biomedical and industrial applications. The
technique seems to be promising because of the inherent efficiency in volumetric
acquisition and high efficiency in radiograph use. Moreover, it permits manufacture
of less costly CT machines. In principle, the CBCT technique allows faster data acqui-
sition than traditional CT. Overall advantages of the CBCT technique are a lower radi-
ation dose, a shorter acquisition time, and reduced costs. Disadvantages of CBCT
include the scattered radiation, the limited dynamic range of the x-ray area detectors,
the truncated-view artifact, and artifacts caused by beam hardening. These draw-
backs need to be considered because they may influence image quality and bone seg-
mentation accuracy.41–44
A large number of different computer-assisted guided implant systems are available
today in clinical practice. Differing levels and quantity of evidence were noted to be
available, revealing a high mean implant survival rate of 96.6% after only 12 months
of observation in different clinical indications. In addition, the mean percentage of
intraoperative complications and unexpected events was 4.6%.45
The accuracy of these systems depends on all cumulative and interactive errors
involved. There is not yet evidence to suggest that computer-assisted surgery is supe-
rior to conventional procedures in terms of safety, outcomes, morbidity, or efficiency.

LASER SYSTEMS IN DENTISTRY

In recent years, various laser systems have gained importance in dentistry as alterna-
tive methods for tooth preparation as well as for soft tissue management.46
The use of laser beam for caries removal allows the preservation of the natural
shape of decayed cavities without the need for preventive extension of prepared
cavities.46
In operative dentistry, some laser wavelengths have the ability to produce a melting
of dentinal surfaces by heat generation, which is potentially helpful in the treatment of
dental hypersensitivity.46
The high potential of disinfection of laser beams can be helpful for the eradication of
infected oral areas and for the treatment of viral tumors. Laser surgery induces a
different process for oral soft tissue healing. The advantages of using the laser
beam in oral surgeries are the reduction of inflammation and postoperative discom-
fort, appreciated quality of healed tissues, disinfection potential, and induction of fibrin
production in lased tissues.46
118 Zandparsa

The use of some wavelengths of laser beams is also beneficial in oral prosthetic sur-
gery. The nonsuturing of the wounds on patients having removable prostheses such
as complete dentures after the ablation by laser beam of tumors or any gingival hyper-
plasia allows the preservation and, in some cases, increase of vestibular length that is
beneficial for the stability and retention of dentures. Laser beams can also be helpful in
oral esthetic applications. The removal of gingival pigmentation (eg, melanin or
metallic tattoo) by laser beams can be performed in a bloodless surgical field, and it
also reduces postoperative discomfort. The use of laser beam seems to be the best
alternative for the treatment of mucositis, which is a common side effect of chemo-
therapy and radiotherapy in patients with cancer.46
Laser in Restorative Dentistry
Alternative technologies for cavity preparation, such as erbium yttrium aluminum
garnet (Er:YAG) laser, have been studied to reduce the inherent stresses, to minimize
the removal of sound tooth structure, and to provide a surface that is more suitable for
adhesive restorative materials.47
When laser light reaches a tissue, it can be absorbed, reflected, scattered, or trans-
mitted to the surrounding tissues. Absorption by water molecules plays a significant
role in thermal reactions.48 Laser energy is absorbed selectively by water molecules
and hydrous organic components of biological tissues in Er:YAG laser irradiation.
Erbium, chromium yttrium scandium gallium garnet (Er,Cr:YSGG) laser is more highly
absorbed by OH ions than water molecules and is expected to have a performance
similar to that of the Er:YAG laser.47 In both erbium lasers, absorption into water
and hydrous organic components occurs quickly, before the absorption into inorganic
components (ie, the cause of heat accumulation)47–49 takes place. Therefore these
two laser systems have been shown to remove enamel and dentin as safely as con-
ventional diamond burs.49–52
Veneer removal
Veneer removal is generally performed with a rotary instrument. With the introduction
of pulsed lasers into dentistry, there may be a beneficial application of such lasers for
removing veneers. The Er:YAG laser energy is transmitted through the veneer, and the
transmitted amount depends on the veneer thickness and composition. The veneer
resin cement absorbs the transmitted energy, which results in an ablation of the
cement. When enough cement is ablated through the veneer it slides off the tooth
surface.53
Laser in Soft Tissue Procedures
Many studies have shown that the use of laser in intraoral soft tissues may result in
increased coagulation, a dry surgical field, and better visualization. Laser increases tis-
sue surface sterilization, which reduces bacteremia, and decreases swelling, edema,
and scarring. Gingival depigmentation using laser ablation has been recognized as an
effective, pleasant, and reliable technique. Finkbeiner in 1994 suggested the useful-
ness of argon laser in soft tissue welding and soldering compared with conventional
tissue closure methods. At present, lasers are used for frenectomy, free gingival graft
procedures, crown lengthening, operculectomy, and many other procedures.54

NANOTECHNOLOGY IN DENTISTRY

Nanotechnology is engineering of molecularly precise structures. These techniques

use molecular machines that are typically equal to or less than 0.1 mm. The prefix
nano means 10 to the minus ninth power (10 9), or 1 billionth. The nanoscale is about
 Latest Biomaterials and Technology 119

a 1000 times smaller than micro, which is about 1/80,000 of the diameter of a human
hair. It is expected that nanotechnology will be developed at several levels: materials,
devices, and systems. At present, the nanomaterials level is the most advanced both
in scientific knowledge and in commercial applications. To understand nanodentistry
requires a background in nanotechnology and nanomedicine. Nanotechnology aims
to manipulate and control particles to create novel structures with unique properties
and promises advances in medicine and dentistry. The growing interest in the future
of medical applications of nanotechnology is leading to the emergence of a new field
called nanomedicine. With nanodentistry, it is possible to maintain comprehensive oral
health care by involving the use of nanomaterials, biotechnology, and ultimately dental
nanorobotics. Nanorobots induce oral analgesia, desensitize teeth, manipulate the
tissue to realign and straighten irregular sets of teeth, and improve durability of teeth.
They also can be used for preventive, restorative, and curative procedures.55,56
Major Tooth Repair
Many techniques have been proposed for tooth repair using tissue engineering proce-
dures, with the goal of replacing the tooth and all the mineral and cellular
components.57,58
Nanorobotic Dentifrice (Dentifrobots)
Development of dentifrobotics could lead to recognition and destruction of the path-
ogens that cause tooth caries. They will be delivered by either mouthwash or tooth-
paste and could be used to fight plaque formation, halitosis, and possibly
calculus.57,59
Dentin Hypersensitivity
Many patients have dentinal hypersensitivity. A goal of dental nanorobotics is to target
the exposed dentinal tubules and to relieve sensitivity.57,59
Orthodontic Nanorobots
Challenges in realignment of natural teeth occur as well as in the timing of tooth move-
ment. Use of orthodontic nanorobotics could affect the timing of tooth movement.57,59
Tooth Durability and Appearance
Tooth durability, appearance, and biocompatibility may be improved by replacing
enamel layers with covalently bonded artificial materials such as sapphire or diamond,
which are 100 times harder than natural enamel or contemporary ceramic veneers.
Like enamel, sapphire is susceptible to acid corrosion, but sapphire can be manufac-
tured in virtually any color, offering cosmetic alternatives. Pure sapphire and diamond
are brittle and prone to fracture if sufficient shear forces are imposed, but they can be
made more fracture resistant as part of the nanostructure of composite materials that
possibly include embedded carbon nanotubes.57,59–62
Nanocomposites are a new restorative nanomaterial that increases tooth durability.
The manufacture of nanocomposites can use nonagglomerated discrete nanopar-
ticles that are homogeneously distributed in resins or coatings to produce nanocom-
posites. The nanofiller includes an aluminosilicate powder with a mean particle size of
about 80 nm and a 1:4 ratio of alumina to silica. The nanofiller has a refractive index of
1.508; it has superior hardness, modulus of elasticity, translucency, esthetic appeal,
excellent color density, high polish, and 50% reduction in filling shrinkage. They are
superior to conventional composites and blend with a natural tooth structure much
better.59,63–65
120 Zandparsa

Strength alone does not explain the relationship of filler to wear resistance. Occlusal
wear occurs by several different mechanisms but mostly caused by abrasive particles
of approximately 0.1-mm diameter that exist within food and that are suspected to be
silica.66
The matrices all composites are subjected to wear. Manufacturers suggest a micro-
protection process in the design of the composite materials so that the filler covers
and protects the matrix from contacting abrasive food particles. This phenomenon
has been seen in some of the available dental composites such as microfills, microhy-
brids, and now in nanohybrids. Nanocomposites could become the composites of
choice in the near future.63
Nanofillers are not all the same. A variety of nanofillers have already been shown. 3M
uses sol-gel technology to produce tiny nanospheres called nanomers, which can be
agglomerated into nanoclusters, and either the spheres or clusters can become filler
particles for composite formulations.67
3M ESPE Filtek Supreme68 uses primarily nanoclusters in combination with submi-
crometer fillers to produce a hybrid. Pentron has had excellent success using polyhe-
dral oligomeric silsesquioxane (POSS) technology borrowed from hybrid plastics.69
Molecular-sized silicate cages are produced from silane and functionalized for core-
action with matrix monomers. This technology has great potential that is still being
explored. Other nanoscale fillers have been designed using tantalum nanoparticles
(Fig. 2A, B).70,71

Implants
Current trends in clinical dental implant therapy include use of endosseous implant
surfaces embellished with nanoscale topography. Nanoscale modification of titanium
endosseous implant surfaces can alter cellular and tissue responses to benefit dental
implant therapy. Three nanostructured implant coatings are in use: diamond, which
possess improved hardness, toughness, and low friction; hydroxyapatite, which pos-
sesses increased osteoblast adhesion proliferation and mineralization; and graded
metalloceramics, which have the ability to overcome adhesion problems (see
Fig. 2C).72

Nanoimpression
Impression material is available with nanotechnology application. Nanofillers are inte-
grated in the vinylpolysiloxanes, producing a unique siloxane impression material. This
material has better flow, improved hydrophilic properties, better model pouring, and
enhanced detail precision.59,64

Nanoanesthesia
One of the most common procedures in dentistry is the injection of local anesthesia,
which can involve long procedures, patient discomfort, and many associated compli-
cations. To induce oral anesthesia in the era of nanodentistry, a colloidal suspension
containing millions of active analgesic micrometer-sized dental robots will be instilled
on the patient’s gingiva. After contacting the surface of the tooth or mucosa, the
ambulating nanorobots reach the pulp via the gingival sulcus, lamina propria, and
dentinal tubules. Once installed in the pulp, the analgesic dental robots may be
directed by the dentist to shut down all sensitivity in any tooth that requires treatment.
After completion of the oral procedure, the dentist directs the nanorobots to restore all
sensation, to relinquish control of nerve traffic, and to egress from the tooth by the
same pathways that were used for ingress.57,59
 Latest Biomaterials and Technology
Fig. 2. Scanning electron micrograph of nanocomposite (Filtek supreme). (A) 1000 and (B) 2500 magnification of a spherical nanocluster of 1 to
4 mm; (C) NanoTite implants. (From Satyanarayana T, Rai R. Nanotechnology: the future. J Interdiscip Dentistry 2011;1:93–100; with permission.)

121
122 Zandparsa

DETECTION AND TREATMENT OF ORAL CANCER

Nanoparticles play a key role in developing new methods for detecting cancer. Detec-
tion of cancer in an early stage is a critical step in improving cancer treatment. The
various nanoparticles used are cantilever, nanopore, nanotubes, and quantum dot.
As cancer cells secrete their molecular products, the antibodies coated on the canti-
lever fingers selectively bind to these secreted proteins. The physical properties of the
cantilever change in real time and provide information about the presence and also the
concentration of different molecular expressions. A simple device for studying single
molecule interactions, called a nanomechanical force gauge, has been developed,
which consists of nanocantilevers fabricated from single-crystal silicon, an etched
nanometer reading scale, and a light microscope to read cantilever deflection along
reading scale.72
Another nanodevice is nanopore. Improved methods of reading genetic code will
help researchers in detecting errors in genes that may contribute to cancer. Nano-
pores contain tiny holes that allow DNA to pass through 1 strand at a time, making
DNA sequencing more efficient.73 Nanotube carbon rods about half the diameter of
a molecule of DNA will not only detect the presence of altered genes but also pinpoint
the location of those changes. Carbon nanotubes can be used as sensors for cancer
drugs and other DNA-damaging agents inside living cells. Carbon nanotubes fluo-
resce near infrared light, whereas human tissue does not. The interaction between
DNA and the DNA disrupter changes the intensity or wavelength of the fluorescent
light emitted by nanotubes.72

Quantum Dots
These are tiny crystals that glow when they are stimulated by ultraviolet light. When
injected into the body, they drift until encountering cancerous tissue. The cells then
attach to a coating on the glowing dots. The light particles show doctors where the
disease has spread.72

Treatment of Oral Cancer

A single dendrimer can carry a molecule that recognizes cancer cells, a therapeutic
agent to kill those cells, and a molecule that recognizes the signal of cell death. Den-
drimer nanoparticles have shown promise as drug delivery vehicles capable of target-
ing tumors with large doses of anticancer drugs. Nanoshells have a core of silica and a
metallic outer layer. By manipulating the thickness of the layer, scientist can design
beads to absorb near-infrared light, creating an intense heat that is lethal to cancer
cells. The physical selectivity to cancer lesion sites occurs through a phenomenon
called enhanced permeation retention.72

Decay-resistant Teeth
Researchers at the Clarkson Advanced Materials Center have found a way to use
nanotechnology to help protect almost any teeth or surface from caries. This protec-
tion is achieved by polishing teeth with silica that is made from nanoparticles. This ma-
terial is 90,000 times smaller than a grain of sand.72,73

Surface Disinfectant
EcoTrue is a surface disinfectant that safely kills 100% of human immunodeficiency
viruses and other particles. It has been used to sterilize tools and incisions to prevent
postoperative infections (EnviroSystems).72
 Latest Biomaterials and Technology 123

Nanotechnology could have a profound effect on dentistry. Once nanomechanics

are available, programmable and controllable microscale robots comprising nano-
scale parts fabricated to nanometer precision will allow dentists and doctors to
perform curative and reconstructive procedures at the cellular and molecular levels.
Before that, they the safety norms must be fulfilled. The current materials available
from nanotechnology through green nanotechnology have fulfilled the safety norms,
and have improved qualities compared with the previous technologies.74

TISSUE ENGINEERING

In the last decade, there has been a substantial and growing awareness of a new field
of applied biologic research called tissue engineering, which builds on the interface
between materials science and biocompatibility, and integrates cells, natural or syn-
thetic scaffolds, and specific signals to create new tissues. This field promises to
have enormous clinical potential, including in dentistry.
To date, most of the procedures performed in dentistry are limited to the replace-
ment of damaged tissues with biocompatible synthetic materials that may not pre-
sent chemical, biological, or physical characteristics and behaviors similar to the
host tissues. These discrepancies, together with the hostile environment of the oral
cavity, result in short-lived successful outcomes and frequent need for retreatment.
Tissue engineering is a multidisciplinary field focused on the development of mate-
rials and strategies to replace damaged or lost tissues with biologic materials by
merging principles, methods, and knowledge of chemistry, physics, engineering,
and biology.75
The concept underlying tissue engineering was first proposed in the United States in
the mid-1980s in order to reduce the donor scarcity for organ transplantation. The
classic cell-based tissue engineering approach involves the seeding of biodegradable
scaffolds with cells and/or growth factors, and then implanting it in order to induce and
conduct tissue growth. The key ingredients for tissue engineering are stem cells, the
morphogens or growth factors that regulate their differentiation, and a scaffold of
extracellular matrix that constitutes the microenvironment for their growth.75
The principal objectives of the current clinical approaches to tissue replacement
and reconstruction are to alleviate pain and to restore mechanical stability and func-
tion. Current strategies for treatment of lost tissues include the use of autogenous
grafts, allografts, and synthetic materials (alloplasts). Although all of these treatment
approaches have had successes and have been major advances in medicine, each
of them has limitations.76

Strategies to Engineer Tissue

Strategies used to engineer tissue can be categorized into 3 major classes: conduc-
tive, inductive, and cell transplantation approaches (Fig. 3).77
Conductive approaches use biomaterials in a passive manner to facilitate the
growth or regenerative capacity of existing tissue; for example, the use of barrier
membranes in guided tissue regeneration and osseointegration of dental implant.77
Inductive approaches involve activating cells in close proximity to the defect site
with specific biological signals. The origins of this mechanism are rooted in the discov-
ery of bone morphogenetic proteins (BMPs). These proteins are now available in re-
combinant forms and are produced on a large scale by biotechnology companies.
BMPs have been used in many clinical trials and are promising as a means of therapy
and supplementation in the regeneration and repair of bone in a variety of situations,
including nonhealing fractures and periodontal disease.77
124 Zandparsa

Fig. 3. Tissue engineering strategies. Three different tissue engineering approaches:

conductive, inductive, and cell transplantation. (From Alsberg E, Hill E, Mooney DJ. Cranio-
facial tissue engineering. Crit Rev Oral Biol Med 2001;12(1):64–75; with permission.)

Cell transplantation approaches involve direct transplantation of cells grown in the

laboratory. The cell transplantation strategy reflects the multidisciplinary nature of tis-
sue engineering, because it requires the clinician or surgeon, the bioengineer, and the
cell biologist.77
A common feature to all three of the tissue engineering strategies is that they typically
involve the use of polymeric materials. In conductive approaches, the polymer is used
primarily as a barrier membrane for the exclusion of specific cells that may disturb the
regenerative process. Inductive approaches typically use a carrier or vehicle for the
delivery of proteins (eg, BMP) or the DNA (gene) that encodes the protein.77

FOUNDATIONS OF TISSUE ENGINEERING

The 3 tissue engineering fundamental elements are cells, scaffold, and cell signaling.

Cells
Stem cells are clonogenic cells capable of self-renewal and capable of generating
differentiated progenies. These cells are responsible for normal tissue renewal as
well as for healing and regeneration after injuries.

Scaffolds
Scaffolds are temporary frameworks used to provide a three-dimensional microenvi-
ronment in which cells can proliferate, differentiate, and generate the desired tissue.
The design of the ideal scaffold for each tissue to be formed is a challenging task.
Scaffolds are usually made from ceramics, natural or synthetic polymers, or
 Latest Biomaterials and Technology 125

composites of these materials. The choice of scaffold material depends on the desired
outcome, thus physical as well as chemical characteristics must be considered.75
Several fabrication technologies have been applied to process biodegradable and
bioresorbable materials into three-dimensional polymeric scaffolds of high porosity
and surface area.78–80
The scaffold degradation is fundamental to achieve success in tissue engineering
therapies. It should ideally reabsorb once it has served its purpose of providing a tem-
plate for tissue regeneration. The degradation must occur at a rate compatible with the
new tissue formation.75

Cell Signaling
Cell signaling is part of a complex system of communication that governs cell activities
and organizes their interactions. The surface of scaffolding materials is important in
tissue engineering because the surface can directly affect cellular response and ulti-
mately the tissue regeneration. An ideal tissue engineering scaffold should mimic
extracellular matrix (ECM) and positively interact with cells, including enhanced cell
adhesion, growth, migration, and differentiated function. Although a variety of syn-
thetic biodegradable polymers have been used as tissue engineering scaffolding ma-
terials, they often lack biological recognition.81,82

TISSUES OF SIGNIFICANCE TO THE ORAL-MAXILLOFACIAL COMPLEX

The effect that tissue engineering may have in dentistry stems from its widespread
application to many different types of tissues related to the oral cavity, including
bone, cartilage, skin and oral mucosa, dentin and dental pulp, and salivary glands.75,83

Bone
Tissue engineering will likely have its most significant impact in dentistry via bone tis-
sue engineering and regeneration.75,83

Cartilage
The limited capacity of cartilaginous tissue to regenerate and the lack of inductive mol-
ecules have focused interest among researchers and manufacturers in developing cell
transplantation approaches to engineer cartilage. Transplantation of cells without a
carrier is now used clinically to repair small articular cartilaginous defects. Investiga-
tors have also shown in animal models that new cartilaginous tissue with precisely
defined sizes and shapes relevant to maxillofacial reconstruction (eg, nasal septum,
temporomandibular joint) can be engineered using appropriate biodegradable scaf-
folds for transplanting the cells.84–86

Skin and Oral Mucosa

The most successful application of tissue engineering to date is the development of
skin equivalents. Skin with both dermal and epidermal components is grown in the
laboratory using a combination of cells and various polymer carriers, and engineered
skin products were the first tissue-engineered products approved by the US Food and
Drug Administration for clinical use. A similar approach has also been developed for
the replacement of oral mucosa.79,80
Various gene-delivery methods are available to administer growth factors to peri-
odontal defects, offering great flexibility for tissue engineering.77
To date, the regeneration of small to moderate-sized periodontal defects using
engineered cell-scaffold constructs is technically feasible, and some of the current
126 Zandparsa

concepts may represent alternatives for selected clinical scenarios. However, the pre-
dictable reconstruction of the normal structure and functionality of a tooth-supporting
apparatus remains challenging.75

Dentin and Dental Pulp

The production of dentin and dental pulp has also been achieved in animal and labo-
ratory studies using tissue engineering strategies. There is now evidence suggesting
that even if the odontoblasts (cells that produce dentin) are lost because of caries, it
may be possible to induce formation of new cells from pulp tissue using certain
BMPs. These new odontoblasts can synthesize new dentin. Tissue engineering of
dental pulp may also be possible using cultured fibroblasts and synthetic polymer
matrices.81,82,87
Restorative dentistry is trying to develop techniques and materials to regenerate the
dentin-pulp complex in a biological manner.88 Tissue engineering-based approaches
have the potential to do this. The regeneration of the dentin-pulp complex with stem
cells might be clinically achievable. However, this may not be applicable to all clinical
scenarios (ie, old teeth with small pulp chambers and root canals and with closed
apices).89

Salivary Glands
The most challenging goal of tissue engineering is replacement of complete organs,
and significant progress has been made in efforts to engineer salivary gland function.
One method of treating salivary gland functional deficiencies makes use of an induc-
tive gene therapy approach. The aim in this approach is to make existing nonsecretory
ductal epithelial cells (following irradiation therapy) into secretory cells capable of fluid
movement. Success in animal models has been shown. Another method to restore
salivary gland function uses cell transplantation. The development of an artificial sali-
vary gland substitute composed of polymer tube lined by epithelial cells has been initi-
ated. This simple device could engraft into the buccal mucosa of patients whose
salivary gland tissue has lost function or been destroyed, and would have the physi-
ologic capacity to deliver an aqueous fluid to the mouth via the buccal mucosa. These
new approaches could be effective for treating conditions associated with lost salivary
gland function, including dysphagia, dysgeusia, rampant caries, and mucosal
infections.90–92

USE OF STEM CELLS FOR TEETH REGENERATION

Nonbiological approaches have been broadly used for restoring loss of teeth for cen-
turies. Materials such as gold, sapphire, and stainless steel were all used as teeth
replacements throughout the generations. However, these devices all induce foreign
body reactions and run the risk of rejection by the immune system, and thus biocom-
patibility is a requirement for the next generation of tooth replacements.93
Regenerative medicine offers opportunities to replace or restore tissues of the body
after disease and trauma. Biomimetic restorations for partial teeth structures, such as
dentin and periodontal ligament (PDL), have also been in development for several
years.93,94
Use of stem cells, either of embryonic or postnatal derivation, for tissue engineering
is attractive because it offers greater scope for using cell fate to try to mimic physio-
logic tissue architecture.95 Although tooth development is a complex process gov-
erned by redundant and reiterative signaling with temporal and spatial protein
expression patterns, efforts have been undertaken by including morphogens such
 Latest Biomaterials and Technology 127

as BMP, and delivery of platelet-derived growth factor gene therapy vectors, which
has resulted in partial dental tissue regeneration.93

STEM CELL CLASSIFICATION

Stem cells are cells that have the ability to divide for indefinite periods in culture, and to
give rise to specialized cells. The cells may be classified according to their origin as
embryonic stem cells, embryonic germ stem cells, or adult stem cells. As the name
implies, embryonic stem cells come from embryos that have developed from eggs
that have been fertilized in vitro. These embryos, used with the consent of the donors,
were leftovers from in vitro fertilization clinics. Separated from the other parts of the
early developing embryo, primitive cells can be grown in a culture medium to become
embryonic stem cells. These cells are not derived from eggs fertilized within the
body.96
Embryonic germ cells are similar to embryonic stem cells except that they are
collected from the fetus later in development. The cells come from a region known
as the gonadal ridge, which later develops into the sex organs. Because the cells
are farther along the development process, they are limited in their ability to give
rise to organs of the body.96 Adult stem cells originate in a mature organism and
help maintain and repair the tissues in which they are found. These stem cells are
responsible for replacing blood and tissues on a regular basis. One advantage of using
adult stem cells is that samples of tissues, or even patients’ own cells, can be used for
implantation, avoiding problems of rejection. Furthermore, the use of adult cells does
not involve the ethical issues that accompany embryonic research.96

Dental Stem Cells

Several populations of cells with stem cell properties have been isolated from different
parts of the tooth. These include cells from the pulp of both exfoliated (children’s) and
adult teeth, from the PDL that links the tooth root with the bone, from the tips of devel-
oping roots, and from the tissue (dental follicle) that surrounds the unerupted tooth.97
The first stem cells isolated from adult human dental pulp were termed dental pulp
stem cells (DPSCs) and were isolated from permanent third molars. In addition, in vivo
transplantation into immune-compromised mice showed the ability of DPSCs to
generate functional dental tissue in the form of complexes similar to dentine/pulp.
Further characterization revealed that DPSCs were also capable of differentiating
into other mesenchymal cell derivatives in vitro, such as odontoblasts, adipoctyes,
chondrocytes, and osteoblasts. DPSCs differentiate into functionally active neurons,
and implanted DPSCs induce endogenous axon guidance, suggesting their potential
as cellular therapy for neuronal disorders.97
Stem cells from human exfoliated deciduous teeth (SHED) have become an attrac-
tive alternative for dental tissue engineering. The use of SHED might bring several
advantages for tissue engineering compared with the use of stem cells from adult
human teeth:
 SHEDS were reported to have higher proliferation rate and increase cell popula-
tion doublings compared with stem cells from permanent teeth. This property
might facilitate the expansion of these cells in vitro before replantation.95
 SHED cells are retrieved from a tissue that is disposable and readily accessible in
young patients.95
Commercial banking of these cells is becoming widespread to enable them to be
used once the child becomes an adult. Limited studies have shown that frozen
128 Zandparsa

SHED cells maintain their properties after cryopreservation for 2 years, but one caveat
is that the effects of long-term storage (>10 years) have not yet been assessed.
Because children naturally lose 20 deciduous teeth, there are multiple opportunities
to bank these cells (unlike cord blood, for example).95
PDL Stem Cells
The PDL is a fibrous connective tissue that contains specialized cells located between
the bonelike cementum and the inner wall of the alveolar bone socket, which acts as a
shock absorber during mastication. The PDL has long been recognized to contain a
population of progenitor cells. Several recent studies identified a population of stem
cells from human PDL that were capable of differentiating along mesenchymal cell lin-
eages to produce cementoblastlike cells, adipocytes, and connective tissue rich in
collagen I in vitro and in vivo. These cells form cementumlike tissue when transplanted
into severe combined immunodeficiency mice. They also show the capacity to form
collagen fibers, highlighting their potential for PDL regeneration.97
Tooth Regeneration
Tissue engineering approaches have proved to be useful for dental tissue and whole-
tooth regeneration strategies. Based on preclinical cell and gene therapy strategies
used for soft tissue organs, reports of the emerging use of tissue engineering strate-
gies for dentin, pulp, and cementum as an alternative to commonly used root canal
and crown therapies are becoming more numerous.98
Because bioengineered tooth crown formation requires the interactions of both
dental epithelial cell progenitors and mesenchymal cell progenitors (as in natural tooth
formation), the ability to bioengineer a tooth of specified size and shape depends on
the ability to first identify, and then guide, the interactions of both types of cells.98
Stem Cell Therapies
Dental caries is one of the most prevalent diseases in the world. In the United States,
more than 50% of children, 85% of adults aged more than 18 years, and more than
50% of the elderly aged more than 75 years have caries lesions.99
Researchers have been able to grow human DPSCs in the laboratory to create both
soft tissues and mineralized dentin. The problem has been that the ameloblasts die off
by a process of apoptosis during tooth development. However, it has been possible to
establish ameloblast cell lines from rodents. The next milestone for scientists is to
refine the technology to use DPSCs and ameloblasts as part of tissue engineering
to synthesize bioengineered replacement tooth substance with a controllable struc-
ture and morphology. Once this has been accomplished, it is expected that bio-
engineered tooth filling materials will quickly become commercially available.
Bioengineered filling materials will be attached to existing tooth structure that is not
in contact with the systemic immune system; therefore, the risk of these materials
creating immune-rejection reactions is very low.99
In the future, the pulp tissue may be regenerated using stem cell therapy. The tissue
engineering of the dental pulp is less complex than the tissue engineering of a whole
tooth, because it is protected inside the tooth, which contributes to the success of
stem cell therapy as part of endodontic treatment.99
Whole-tooth Regeneration
The ultimate goal in dentistry is to have a method to replace lost teeth biologically;
a cell-based implant rather than a metal one. The minimum requirement for a biolog-
ical replacement is to form the essential components required for a functional tooth,
 Latest Biomaterials and Technology 129

Fig. 4. The process for tissue engineering of a replacement tooth. (Data from Garcia-Godoy F,
Murray PE. Status and potential commercial impact of stem cell-based treatments on dental
and craniofacial regeneration. Stem Cells Dev 2006;15(6):881–7.)

including roots, PDL, and nerve and blood supplies. The visible part of the tooth, the
crown, is less important because, although essential for function, synthetic tooth
crowns function well, and can be perfectly matched for size, shape, and color. There-
fore, the challenge for biological tooth replacement is to form a biological root
(Fig. 4).94,97,100

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