Original Article

3D Printing of Personalized Artificial

Bone Scaffolds
Shailly H. Jariwala,1 Gregory S. Lewis,1,2 Zachary J. Bushman,3 James H. Adair,4 and Henry J. Donahue1,2,5

Abstract

Additive manufacturing technologies, including three-dimensional printing (3DP), have unlocked new possibilities for bone
tissue engineering. Long-term regeneration of normal anatomic structure, shape, and function is clinically important subsequent
to bone trauma, tumor, infection, nonunion after fracture, or congenital abnormality. Due to the great complexity in structure
and properties of bone across the population, along with variation in the type of injury or defect, currently available treatments
for larger bone defects that support load often fail in replicating the anatomic shape and structure of the lost bone tissue. 3DP
could provide the ability to print bone substitute materials with a controlled chemistry, shape, porosity, and topography, thus
allowing printing of personalized bone grafts customized to the patient and the specific clinical condition. 3DP and related
fabrication approaches of bone grafts may one day revolutionize the way clinicians currently treat bone defects. This article gives
a brief overview of the current advances in 3DP and existing materials with an emphasis on ceramics used for 3DP of bone
scaffolds. Furthermore, it addresses some of the current limitations of this technique and discusses potential future directions
and strategies for improving fabrication of personalized artificial bone constructs.

Introduction modification, and differences in limited using traditional manufacturing

structure of bones from different sites of techniques.3
Bone defects resulting from severe the body suggest the need for alternative
trauma, nonunion after fracture, tumor methods.1,2 Structural allografts provide Because of the above drawbacks of
removal, infection, or congenital scaffolds with a range of different shapes allografts and autografts, CaP cements
abnormalities are often too large to heal and sizes, but are associated with limited have been investigated for application
on their own and can lead to long-term revascularization2 and risks of infection, as  bone graft substitutes due to their
deformity such as limb shortening, immunological rejection,3 and long-term injectability and ability to harden at body
leaving patients with reduced bone mechanical failure. Sintered blocks of temperature.4 Although CaP cements are
structure and function. Autografts are calcium phosphates (CaP) such as osteoconductive (when the bone graft
considered the clinical gold-standard tricalcium phosphate (TCP) and material serves as a scaffold for new bone
treatment for bone defects because they hydroxyapatite are used as bone growth), there are still crucial issues such
include a scaffolding structure along substitute materials due to their chemical as weak cohesion of solid–liquid phase,
with cells and other biologics from the similarity to the organic apatite crystals intrinsic microporosity, and disintegration
same patient. However, donor- site of bone.3 However, they may require upon contact with blood or body fluids
morbidity, limited availability for intraoperative modifications and the that need to be addressed to satisfy
harvesting, requirement of intraoperative ability to fabricate microstructures is clinical needs. 5 Furthermore, with

1
Division of Musculoskeletal Sciences, Department of Orthopaedics and Rehabilitation, and 5Department
of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania.
2
Department of Biomedical Engineering, Penn State College of Engineering, University Park, Pennsylvania.
3
Chemistry Department, Eberly College of Science, and 4Materials Science and Engineering, College of
Earth and Mineral Sciences, Pennsylvania State University, University Park, Pennsylvania.

56 3D PRINTING MARY ANN LIEBERT, INC. • VOL. 2 NO. 2 • 2015 • DOI: 10.1089/3dp.2015.0001
 Personalized 3D-Printed Bone Scaffolds

injectable CaP pastes it is difficult to

control porosity, surface topography, and
shape of the graft. It is also challenging to
create a composite graft material having
mechanical properties similar to cortical
or cancellous bone.

Another concern in developing

efficacious bone graft substitutes or a
scaffold is that significant variation in
bone anatomy exists between patients.
Furthermore, defect shape and size will
be variable depending on the type of
defect.6,7 These anatomical characteristics
must be considered during graft fixation
and design in order to improve graft
osseointegration with host tissue. This
suggests the need for using additive
manufacturing (AM) technology along
with computer-aided design (CAD) so
that bone grafts or scaffolds with
complex shapes, identified in patients via
medical imaging techniques such as
computed tomography (CT) and
magnetic resonance imaging, can be Figure 1. Schematic comparing various 3DP modalities discussed in this article.
manufactured.8,9 These grafts or scaffolds Stereolithography uses light (UV) to cross-link photopolymer liquids that polymerizes layer-by-layer
could then be used in biomedical by immersion of a platform downward into the liquid. Fused deposition modeling, on the other
applications ranging from customized hand, involves deposition of a melted thermoplastic (filaments) by extrusion through a nozzle.
medical implant design to tissue Selective laser sintering modality uses long-wavelength lasers (or a high-energy light source) to
engineering.10,11 AM also has the distinct fuse beads of material one layer at a time, whereas powder 3DP does the same using a binder
advantage of enabling scaffolds or solution that locally hardens the powder bed where the binder is deposited. Ink-jet 3DP involves
artificial constructs to be built with direct printing of liquid (polymer, cells, and biomolecules) using a nozzle and a print head in
predefined micro - as well as order to fabricate tissue engineering constructs. 3DP, three-dimensional printing.
macrostructures.12 Microstructure of
constructs is also important because the extrusion, photopolymerization, high optimized through control of scaffold
pore size, orientation, and surface temperatures, or laser-assisted sintering features such as surface topography.
chemistry on the micron-scale dictate for a layer- by - layer creation of 3D
the extent and nature of vascular and scaffolds, is a direct deposition process17
bone tissue in-growth. (Fig. 1 and Table 1). Unlike other methods, Powder-Based 3DP
3DP enables fabrication of heterogeneous
There are several different AM tissue constructs composed of deposited Materials and Printing Process
techniques, such as three-dimensional cells, growth factors, extracellular matrix
printing (3DP), 13,14 selective laser molecules, and the biomaterial of The 3DP method considered here is
sintering,12,15,16 sheet lamination,12 and interest.18 3DP is also a powder-based a  powder- based ink - jet printing
fused deposition modeling,15,16 that could fabrication method using an ink-jet print technique.20 This technology is useful for
be applied to generate 3D scaffolds head that prints binders on to loose printing bone scaffolds because a variety
(Fig. 1). O’Brien et al.17 provide a concise powders in a powder bed. This allows the of powders (including metal and
overview of the application of these manufacture of personalized 3D models ceramic) and binders can be used. A
different AM techniques for fabrication guided directly from computer data.19 typical 3DP procedure is divided into
of tissue-engineered scaffolds in the For instance, a patient’s CAD data can be four steps. First, a homogenous powder
fields of bone, osteochondral, neural, used for fabrication of customized bed surface is created by spreading fine
and vascular tissue regeneration. Table 1 implants without the need of making a powder granules using a set of rollers.16
summarizes comparisons between mold. Here we describe 3DP procedures, Flowability of the powder is critical for
scaffolds generated using various AM materials used, technical possibilities, and the powder to spread, and is dependent
techniques along with their relative limitations of this technique. The purpose on particle size, shape, and surface
advantages and disadvantages. Among of this commentary is to provide the 3DP roughness.15 The size of the powder
these AM techniques, there has emerged community a concise introduction to granules determines the smoothness and
great interest in 3DP to manufacture AM-based bone tissue engineering, thickness of the powder bed formed,
bone scaffolds. This is because 3DP, including processes and materials, and which in turn affects the resolution of the
unlike other AM techniques that use how bone regenerative medicine may be final printed construct. High flowability

MARY ANN LIEBERT, INC. • VOL. 2 NO. 2 • 2015 • DOI: 10.1089/3dp.2015.0001 3D PRINTING 57
Jariwala et al.

Table 1. Examples of several additive manufacturing techniques used to fabricate scaffolds for
bone tissue engineering
AM technology Printing materials Advantages Disadvantages References

Powder PCL Direct printing Lower green strength 13–14,23–24,35–37,

three-dimensional Hydroxyapatite Wide range of material Postprocessing technique 39–40
printing (binder solution) HA/TCP choice restricts biomolecule
HA/collagen Cost effective incorporation
Ceramics (calcium
phosphates)
Polymers
Composites
Ink-jet bioprinting (direct Polymers (hydrogels) Processing conditions Limiting choice of 17,18
liquid printing) Living cells milder biomaterials
Proteins and Allows for incorporation of High required cell density
biomolecules biomolecules (proteins)
(collagen) and living cells
(multiple cell types)
Fused deposition Thermoplastic polymers No platform or support Material restrictions due to 15–17
modeling (heated (PCL, poly-lactic acid, needed need for melting (require
extrusion) etc.) Higher mechanical filaments of thermoplastic
TCP strengths of printed polymers)
scaffold High temperatures
Fast and inexpensive Cannot incorporate
biomolecules/cells
Difficult to replicate
geometries, low resolution
Not suitable for
musculoskeletal
applications
Selective laser sintering Polymers Higher resolution Requires long-wavelength 12,15–17
(laser source) Ceramics No postprocessing or high-energy source
required (cannot print cells)
Higher mechanical Resolution depends on laser
properties beam diameter
Slow process, expensive
Restricted to stiff materials
Stereolithography Polymers Higher resolution Only applicable with 12
(UV/photopolymerization) (photocrosslinkable) photopolymers
Support structure required
Use of UV light source
restricts incorporation of
biomolecules and living
cells

Summary of different biomaterials used along with advantages and disadvantages between various additive manufacturing (AM) techniques.

and finer size granules permit formation between the nanoparticles, increased the of 6, 18, 29, 35, and 50 μm size. Their
of thin powder layers enabling higher interparticle distance, reduced van der results revealed that it was difficult to
resolution.19 However, fine powder can Waals forces, and improved flowability. print with particles that were either too
agglomerate due to attractive interactions Thus, a trade-off between flowability and small or too large (6 or 50 μm) due to
between spherical particles (van der Waals resolution is unavoidable. Seitz et al.22 issues with low flowability and powder
forces)21 that can dominate gravitational recommends using spherical granules bed stability, respectively. They concluded
forces and reduce flowability, resulting in (e.g., CaP) of mean diameter below that an optimal particle size range for
poor compaction and unacceptable 100 μm to ensure good resolution. getting good printability was between 20
powder bed recoating. However, Butscher Butscher et al.21 conducted a systematic and 35 μm.
et al.21 also subjected their fine powder to evaluation of powder properties such as
plasma treatment with monomer powder size and flowability in order to In the second 3DP step, the print head
hexamethyldisiloxane, which deposited better understand the effect of these sprays binder solution droplets on the
tiny point-like nanostructures on the characteristics on printability of CaP. powder bed in several passes guided by
powder surface that acted as spacers They fabricated and tested CaP powders a  CAD file. The final part consists of

58 3D PRINTING MARY ANN LIEBERT, INC. • VOL. 2 NO. 2 • 2015 • DOI: 10.1089/3dp.2015.0001
 Personalized 3D-Printed Bone Scaffolds

material only at these specific locations. synthetic (e.g., polylactic acid) or 3DP allows manufacturing bone scaffolds
The binder solution can be an organic or naturally occurring (starch, dextrose, with scalability, different anatomical
aqueous solution (e.g., phosphoric acid23 collagen, etc.). Synthetic polymers have geometries, and porosity. Calcium
or dextrin24) that can not only wet the better mechanical properties, quality phosphate bind to living bone, giving
surrounding powder, but also locally control, and degradation rates compared these materials advantages as bone
harden the wetted area.25,26 Binder drop to natural polymers. However, they lack scaffold material. Klammert et al.35
volume and wettability are important integrin - binding ligands and have fabricated brushite (di CaP dihydrate)
parameters to consider before printing. hydrophobic surfaces resulting in lower and monetite (di CaP anhydrous) 3D
Binder wettability influences the green cell proliferation,29 which may necessitate scaffolds to demonstrate the capability of
strength (the initial strength after their surfaces to be modified with 3DP for reconstruction of cranial defects
printing but before postprocessing steps) receptors or hydrophilic coatings. and concluded that 3DP implants
of the printed object, and is directly Natural polymers are hydrophilic and complied with the geometric requirements
related to the powder particle surface can be used with water-based binders, and provided an adequate fit. These
energy, chemistry, and binder viscosity. whereas synthetic polymers require investigators fabricated anatomically
Excessive wetting characteristics can lead organic solvents like chloroform. 19 shaped scaffolds using CAD files
to binder droplet spreading to a larger Collagen is a main organic constituent of generated by scanning a human cadaver
area than specified by the CAD file, bone, and collagen scaffolds demonstrate skull having specific cranial defects. Tada
resulting in poor resolution. 19 excellent biological performance in vivo et al.36 fabricated HA-TCP implants for
Additionally, plasma treatment can due to their high porosity, permeability, reconstruction of facial deformities by
impact wetting characteristics of the and biocompatibility. However, collagen utilizing three-dimensional patient CT
finer particles allowing binder droplets scaffolds are weak and compliant.29 data that were transferred to create a
to displace them.27 Printing thinner life-sized CAD model of the defect,
layers utilizes higher shear forces for which in turn was used for shaping the
Due to their excellent biocompatibility
recoating that require powder bed artificial HA-TCP bone implant. They
and osteoconductivity, CaP ceramic
stabilization. This necessitates applying concluded that anatomically shaped
powders, with acid binders such as
water moisture to the top powder layer templates and implants helped in
phosphoric acid/citric acid, are used
leading to rearrangement of fine powders optimizing the implant design and
widely in bone tissue engineering.13,14,23,30
due to capillary effects.27 resulted in better contouring in cases
There are two main approaches to using
with complex defects. Temple et al.37
ceramic powders in the context of 3DP. In
In the third step, following binder demonstrated feasibility of 3DP
the first approach, sacrificial polymeric
deposition, the printed 2D layer is polycaprolactone (PCL) scaffolds with
binders (that pyrolyze upon sintering)19
allowed to dry. In this step, a new layer of varying pore diameters having the shape
are used to improve green strength. In the
powder is also rolled over the printed of human mandibular and maxillary
second, the binder dissolves ceramic
layer following drying, in order to form bones. Grayson et al.38 successfully
particles and forms new crystals that then
a  powder bed for the next binder developed decellularized bone scaffolds
interdigitate, forming stiffer ceramic
deposition. The above three steps are that were shaped based on human
networks. Composite materials such as
repeated iteratively until the final 3D temporomandibular joints, were seeded
combinations of ceramic (TCP), Bio-
part is printed in a layer-by-layer manner. with human mesenchymal stem cells,
Glass, or polymers (natural polymers like
and were provided appropriate bioreactor
collagen) have also been studied for use
The fourth and last step is de-powdering systems for the maturation of the graft
in 3DP. Composites can be formed either
of the 3D printed part in order to remove before implantation.
during printing using a polymeric binder
any loose powder from the printed body.
with ceramic powder31 or by initially
Postprocessing steps such as sintering19 Seitz et al.13,14,39 investigated the feasibility
starting with a ceramic/polymer powder
and polymer infiltration15,28 have also of fabricating 3DP HA scaffolds with
blend32 and an acid binder. However,
been applied in the case of ceramic 3DP complex internal structures and high
powder and binder materials need to be
to improve mechanical properties, for resolution, using a water-soluble polymer
selected with care as free radical initiators
example, compressive strength, of the binder (Schelofix) and sintering. They
after printing can compromise
printed part or to form a polymer– demonstrated that fabrication of
biocompatibility.33
ceramic composite better mimicking cylindrical scaffolds with inner channel
bone’s natural structure. Sintering at high dimensions down to 450 μm was possible
temperatures, however, produces In Vitro and In Vivo Testing and allowed for osteointegration. 13
significant shrinkage of the printed part. of 3DP Bone Scaffolds Additionally, osteoblastic MT3T3-E1
This must be compensated for by cells attached, proliferated, and
increasing dimensions in the initial CAD Synthetic bone grafts with the greatest maintained their morphology on 3DP
model,24 as shrinkage may change the potential to be efficacious are three- HA scaffolds.14 Another study39 looking
desired resolution. dimensional, biocompatible, and at biocompatibility of 3DP HA, TCP, and
bioresorbable. Grafts should possess bovine HA blocks found, using human
A range of materials, including polymers, sufficient mechanical properties and yet periosteal cells, that 3DP TCP and
ceramics, and composites, can be used be porous, to permit the flow of nutrients, bovine HA blocks were biocompatible.
for 3DP. Polymeric materials can be vascularization, and bone ingrowth.1,16,33,34 These findings are important for bone

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Jariwala et al.

augmentation as periosteal cells are Limitations and Future the postprocessing steps and may result
directly in contact with biomaterials in in vivo cytotoxicity. Thus, selection of
in  many situations. Castilho et al.23
Prospects a more biocompatible binder–powder
fabricated 3D biphasic CaP (BCP) With AM techniques, the overall combination is required. Use of
scaffolds using a hydraulic setting resolution achievable with current polymeric binders that can be resorbed
reaction of HA- TCP powders systems and the range of useable during the postprocessing steps could
incorporating phosphoric acid and materials for developing prototypes are be  one way to address this problem.
posttreatment with polylactic-co-glycolic two limiting characteristics. From an Composites of ceramics using resorbable
acid solution. They demonstrated that engineering perspective, overcoming low glass materials to enhance mechanical
osteoblastic MG63 cell proliferation was mechanical strength, limited resolution, properties could be another potential
greater on BCP composites compared to and slow degradation of 3DP structures solution. The composite scaffold
pure HA or TCP scaffolds. Becker et al.24 are major challenges in developing approach is promising for generation of
fabricated 3DP HA and TCP blocks, as porous ceramic and composite scaffolds stronger, more ductile, ceramic scaffolds,
well as a bovine HA blocks with a central for bone substitutes. Poor mechanical but differences among cortical and
channel, using dextrin as a binder properties can render the ceramic 3DP trabecular bone structures still require
solution for intramuscular bone scaffolds unsuitable for high-load- functionally graded materials, with local
induction in a rat model. They found bearing applications. 3DP HA scaffolds variations in material composition and
that HA and TCP blocks induced new impregnated with bis-GMA43 and TCP- mechanical properties, to be developed.
bone formation demonstrating in vivo sintered scaffolds31 were shown to
biocompatibility. improve mechanical properties. A 10- Micro- and nanoscale features of a
fold increase in compression strength scaffold may also have important effects
More recently, Inzana et al.40 fabricated a (76 MPa) of 3DP TCP and tetra CaP on osseointegration of the scaffold. For
CaP and collagen composite 3D scaffold (TTCP) scaffolds has been reported by instance, osteoblastic and preosteoblastic
using phosphoric acid binder to optimize Khalyfa et al. with sintering as compared cells have been shown to respond in vitro
the cytocompatibility and material to untreated scaffolds (0.7 MPa).28 They to specific nanotopographical features
parameters of 3DP ceramics. Using a also infiltrated the sintered scaffolds with that replicate bone’s native surface
murine segmental defect model, new bismethacrylated oligolactide macromer structure.44,45 Similar features were
bone formation that proceeded primarily (DLM - 1), containing 10 wt % of associated with improved healing of a
through the intramedullary canal was 2-hydroxyethyl methacrylate as co- critical-sized defect in vivo.46 Therefore,
demonstrated. They also demonstrated monomer and observed increases in it may be advantageous to replicate in
periosteal bone formation that the compression strength to 54 MPa as scaffolds the nanotopographical features
incorporated the degrading scaffold compared to untreated scaffolds (slightly of bone’s native surface. However,
material. The biocompatibility and lower than sintered scaffolds). Gbureck scaffolds with nanotopographical
resorbability of 3DP scaffolds, using pure et al. 33 reported an increase in features require higher spatial resolution
HA, β-TCP, and a mixture of HA and compressive strength of biphasic TCP than current 3DP can generally provide.
TCP, was also studied using pre- scaffolds from 0.9 to 8.7 MPa (30  wt% One approach to improving the
osteoclastic RAW264.7 cells.41 RAW264.7 acid concentration) with increasing resolution of 3DP would be to use fine
differentiated into osteoclast-like cells concentrations of phosphoric acid powder granules with higher flowability,
that resorbed CaP surfaces, but large binder. They also observed a fourfold and include an optimal binder solution
lacunae formation was observed only increase in compressive strength from and binder drop volume to avoid
on  the surface of biphasic HA-TCP 5.3 MPa to more than 22 MPa, with aggregation of finer powder particles
composites. This illustrates the influence 20 wt% acid concentration, after repeated that would result in a lower resolution.
of phase composition on resorption of postprinting hardening in diluted
ceramic 3D scaffolds.41 Furthermore, phosphoric acid. Another approach to increasing 3DP
Konopnicki et al.42 fabricated 3DP 50% resolution would be to incorporate
PCL and 50% TCP composite scaffolds particles of a nanoscale size into the 3DP
seeded with porcine bone marrow However, with sintering the minimum “ink” to create nanoscale patterns. This
progenitor cells (pBMP) and implanted pore size achieved thus far, without approach is based on previous work
them for 8 weeks into mandibular defects affecting the resolution of the printed showing that specific nanotopographies
in minipigs. Unseeded scaffolds were ceramic, is 300  μm.28 Also, one of the (60–80 nm but not 15–25 or over
used as controls. They found that outcomes of sintering is nonuniform 100 nm), fabricated from HA, increase
TCP/PCL scaffolds seeded with pBMPs shrinkage, which makes it difficult to adhesion, proliferation, and osteoblastic
provided good bone penetration into the mimic cortical and trabecular bone differentiation of mesenchymal stem
scaffold. They also observed angiogenesis structure as porosities in the scaffold will cells.46 These nanotopographies refer to a
at the center of the construct and around change during sintering. Most polymeric mixed and variable topography, containing
newly formed bone. These studies binders work well in improving strength bumps, islands, and fractal patterns, as
demonstrate the feasibility of using 3D and ductility in the powder–binder shown in Figure 2. The 25–30 nm coating
ink-jet printing for fabricating bone composite materials; however, polymeric had primary islands (900 nm in
scaffolds and also demonstrate their binders are capable of producing residues diameter), and the 50–60 nm coatings
in vitro and in vivo biocompatibility. that might not be easily removed during had secondary islands (200 nm in

60 3D PRINTING MARY ANN LIEBERT, INC. • VOL. 2 NO. 2 • 2015 • DOI: 10.1089/3dp.2015.0001
 Personalized 3D-Printed Bone Scaffolds

diameter) in addition to primary islands,

while the 100–120 nm coating displayed
tertiary islands (40 nm in diameter).46
However, the trough-to-crest heights of
these different nanotopographies were not
significantly different. These studies
suggest that these specific fractal patterns,
and not the trough-to-crest heights, of
the nanotopographies enhance
osteoblastic differentiation and
osteogenic potential. We propose that
these optimized nanotopographic
geometries can be incorporated into 3D
printed scaffolds by incorporating
nanoparticles into the 3DP “ink.” This
approach would create printed nanoscale
geometries not currently attainable with
traditional AM technologies.

Figure 2. Schematic of the different HA nanotopographies (25–30, 50–60, and 100–120 nm) We are developing a technique wherein
showing the varied fractal patterns and islands. Secondary island formation was observed piezo-electric (SonoPlot, SonoPlot, Inc.,
with 50–60 nm topography, while tertiary islands were observed on the 100–120 nm Middleton, WI) 3DP (Fig. 3) is used
topography. to  print a suspension of calcium

Figure 3. Schematic of a 3DP approach to develop personalized bone scaffolds with a lip that matches the cross section geometry of the
defect. (a) A micro-CT scan of the patient or animal model, combined with computer modeling and design, can be used to obtain the
geometry of the defect that can be replicated during the bone graft fabrication. The personalized lip would provide additional support and
fixation. (b) Illustration of the piezo-electric 3D printer. (c) Schematic showing the process of piezo-electric 3DP. The ultrasonic vibrations via
the piezoelectric are used to deploy the colloidal suspension of calcium phosphosilicate particles of different diameters (20–100 nm) in
polyvinylpyrrolidone.

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Jariwala et al.

In summary, 3DP and other AM

approaches are promising technologies
for developing artificial bone constructs
or scaffolds that are equally as osteogenic
as autografts or allografts. Furthermore,
there is a strong potential to use medical
imaging combined with computer
modeling and design to develop artificial
bone grafts personalized to an individual
patient’s particular defect.

Acknowledgments
This work was supported by National
Center for Research Resources grant KL2
TR000126 (GSC), National Institute of
Arthritis and Musculoskeletal Diseases
grant R01 AR54937 (HJD), and the
Figure 4. Computer-generated image of the proposed personalized artificial bone scaffold Musculoskeletal Transplant Foundation
with 3D nanotopography. The balls are calcium phosphosilicate nanoparticles that can range (HJD).
in diameters of 10–100 nm. We envision that particles of only one given size would be used in
a given construct. As the construct is resorbed, the nanotopographic surface would remain
constant.
Author Disclosure Statement
phosphosilicate particles of different biomaterials not amenable to 3DP. In this No competing financial interests exist.
d i am e t e r s (20–100 nm) in case, etching could be used to apply the
polyvinylpyrrolidone. This will result in desired nanotopgraphy on the surfaces of
a scaffold composed of calcium the scaffold. An advantage of a lost-mold References
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