Rapid prototyping in tissue engineering: challenges and potential

Review TRENDS in Biotechnology Vol.22 No.12 December 2004 

Rapid prototyping in tissue 

engineering: challenges and potential 

Wai-Yee Yeong 1 , Chee-Kai Chua 1 , Kah-Fai Leong 1 and Margam Chandrasekaran 2 

1 

Rapid Prototyping Research Laboratory, Design Research Centre, School of Mechanical and Production Engineering, 

Nanyang Technological University, Singapore 639798 

2 

Forming Technology Group, Singapore Institute of Manufacturing Technology, Singapore 638075 

Tissue engineering aims to produce patient-specific 

biological substitutes in an attempt to circumvent the 

limitations of existing clinical treatments for damaged 

tissue or organs. The main regenerative tissue engineering 

approach involves transplantation of cells onto 

scaffolds. The scaffold attempts to mimic the function of 

the natural extracellular matrix, providing a temporary 

template for the growth of target tissues. Scaffolds 

should have suitable architecture and strength to serve 

their intended function. This paper presents a comprehensive 

review of the fabrication methods, including 

conventional, mainly manual, techniques and advanced 

processing methods such as rapid prototyping (RP) 

techniques. The potential and challenges of scaffoldbased 

technology are discussed from the perspective of 

RP technology. 

Tissue engineering has gained more attention in the past 

decade, owing to its success in enabling tissue regeneration 

for therapeutic purposes. It is an interdisciplinary 

field which applies the principles of engineering and life 

sciences to the development of biological substitutes that 

restore, maintain or improve tissue function [1]. 

Tissue engineering aims to produce patient-specific 

biological substitutes in an attempt to circumvent the 

limitations of existing clinical treatments for damaged 

tissue or organs. These limitations include shortage of 

donor organs, chronic rejection and cell morbidity. The 

main regenerative tissue engineering approaches include 

injection of cells alone, development of encapsulated 

systems and transplantation of cells onto scaffolds [2]. 

The latter approach appears to be the dominant method 

used in research on tissue engineering because it permits 

experimental manipulation at three levels to achieve 

optimal construct: the cells, the polymer scaffolds and 

the construction method [3]. 

The scaffold attempts to mimic the function of the natural 

extracellular matrix. The primary roles of scaffold are: (i) to 

serve as an adhesion substrate for the cell, facilitating the 

localization and delivery of cells when they are implanted; 

(ii) to provide temporary mechanical support to the newly 

grown tissue by defining and maintaining a 3D structure 

and (iii) to guide the development of new tissues with the 

appropriate function [4]. 

Corresponding author: Chee-Kai Chua (mckchua@ntu.edu.sg). 

Available online 2 November 2004 

www.sciencedirect.com 0167-7799/$ - see front matter Q 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tibtech.2004.10.004 

A successful scaffold should possess the following 

characteristics [5]: (i) a suitable macrostructure to 

promote cell proliferation and cell-specific matrix production; 

(ii) an open-pore geometry with a highly porous 

surface and microstructure that enables cell ingrowth; 

(iii) optimal pore size employed to encourage tissue 

regeneration and to avoid pore occlusion; (iv) suitable 

surface morphology and physiochemical properties to 

encourage intracellular signaling and recruitment of 

cells and (v) being made from a material with a predictable 

rate of degradation, with a nontoxic degraded material. 

Scaffolds can be produced in a variety of ways, using 

conventional techniques or advanced processing methods. 

Conventional scaffold fabrication methods 

Conventional methods for manufacturing scaffolds 

include solvent casting and particulate leaching [6], gas 

foaming [7], fiber meshes and fiber bonding [8], phase 

separation [9], melt molding [10], emulsion freeze drying 

[11], solution casting and freeze drying [12]. However, 

there are inherent limitations in these processing 

methods, which offer little capability precisely to control 

pore size, pore geometry, pore interconnectivity, spatial 

distribution of pores and construction of internal channels 

within the scaffold (Figure 1). 

Figure 1. Scaffold produced using conventional freeze-drying method. The pores 

formed are interconnected but inhomogeneous owing to the random freezing 

kinetics. The architecture of the pores can be adjusted by controlling the freezing 

kinetics of the solution. A dense layer of ‘skin’ is formed at the open surface, which 

greatly affects the diffusion efficiency of the scaffold.

644 


Consequently, researchers try to modify the conventional 

techniques to overcome these inherent process 

limitations. Kim and Mooney [13] produced polyglycolic 

acid (PGA) fibers bonded with poly-L-lactide (PLLA) to 

enhance the mechanical strength and the degradation 

rate of the unbonded PGA fiber meshes. As a variant to the 

freeze-drying process, Ho et al. [14] prepared scaffolds 

using a freeze-extraction method, which was relatively 

more time- and energy efficient. Murphy et al. [15] 

enhanced pore interconnectivity by fusing the porogen 

together to form a template, instead of using unbounded 

particles in so1vent casting/particulate leaching process. 

The result showed that holes were formed in pore walls, 

guaranteeing pore interconnectivity. Chen and Ma [16] 

created nanofibrous PLLA scaffolds which incorporated 

interconnected spherical macropores. The macropores 

were voids left by paraffin spheres, which were thermally 

bonded before the casting of the polymer solution. In place 

of paraffin spheres, Gross and Rodríguez-Lorenzo [17] 

used a sintered salt template to produce PLLA-reinforced 

apatite scaffolds. 

Notwithstanding the improvements that have been 

attained, the control over scaffold architecture using these 

conventional techniques is highly process dependent 

rather than design dependent. As a result, RP is seen to 

be a viable alternative for achieving extensive and 

detailed control over scaffold architecture [18,19]. 

Advanced scaffold-fabrication methods 

RP is a common name for a group of techniques that can 

generate a physical model directly from computer-aided 

design data. It is an additive process in which each part is 

constructed in a layer-by-layer manner. Table 1 presents 

and compares the RP techniques that can be used to 

fabricate scaffolds directly or indirectly. 

Direct RP fabrication method 

RP systems such as fused deposition modeling (FDM), 3D 

printinge (3-DP) and selective laser sintering (SLS) have 

been shown to be feasible for producing porous structures 

for use in tissue engineering. In this review, the tissue 

scaffold fabrication techniques are categorized by virtue of 

their mode of assembly into one of two processes: the melt– 

dissolution deposition technique and the particle bonding 

technique. 

Melt–dissolution deposition technique 

In a typical melt–dissolution deposition system, each layer 

is created by extrusion of a strand of material through an 

orifice while it moves across the plane of the layer crosssection. 

The material cools, solidifying itself and fixing to 

the previous layer [20]. Successive layer formation, one 

atop another, forms a complex 3D solid object. 

Porosity in the horizontal XY plane is created by 

controlling the spacing between adjacent filaments 

(Figure 2). The vertical Z gap is formed by depositing the 

subsequent layer of filaments at an angle with respect to 

the previous layer. Repetitive pattern drawing will 

produce a porous structure ready to be used as a scaffold. 

A representative system using melt–dissolution 

www.sciencedirect.com 

deposition is FDM. This method spins off several new 

systems that operate under similar principles. 

FDM: In this method, a filament of a suitable material 

is fed and melted inside a heated liquefier before being 

extruded through a nozzle. The system operates in a 

temperature-controlled environment to maintain sufficient 

fusion energy between each layer. 

Researchers have demonstrated the feasibility of 

utilizing FDM to fabricate a functional scaffold directly. 

Zein et al. [21] fabricated polycaprolactone (PCL) scaffolds 

with a honeycomb structure and a channel size of 160– 

770 mm. Samar et al. [22] have successfully produced a 

polymer-ceramic composite scaffold made of polypropylene-tricalcium 

phosphate (PP-TCP). The scaffolds were 

reported to have a pore size of 160 mm and a mechanical 

strength of 12.7 MPa, which is comparable to the tensile 

strength of natural cancellous bone, which has a value of 

7.4MPa [23]. In a recent study, human mesenchymal 

progenitor cells were seeded on PCL and PCL-hydroxyapatite 

(HA) scaffolds fabricated by FDM [24]. Proliferation 

of cells toward and onto the scaffold surfaces was detected. 

Drawbacks of the FDM technique include the need for 

input material of a specific diametric size and material 

properties to feed through the rollers and nozzle. Any 

changes in the properties of the material require effort to 

recalibrate the setting of the feeding parameters. As a 

result, FDM has a narrow processing window. The 

resolution of FDM is relatively low, at 250 mm. In FDM, 

a limited range of material s can be used, with almost 

complete exclusion of natural polymers, as the material 

used must be made into filaments and melted into a semiliquid 

phase before extrusion. The operating temperature 

of the system is too high to incorporate biomolecules into 

the scaffold, hence limiting the biomimetic aspects of the 

scaffold produced. Moreover, the material deposited 

solidifies into dense filaments, blocking the formation of 

microporosity. Microporosity is an important factor in 

encouraging neovascularization and cell attachment [25]. 

Modifications of FDM to circumvent these limitations 

have encouraged the emergence of several new techniques. 

These include techniques that eliminate the 

requirement of precursor filaments or a system with 

reduced operating temperatures. Some variants of the 

FDM process include the 3D fiber-deposition technique 

[26], precision extruding deposition (PED) [27] and precise 

extrusion manufacturing (PEM) [28]. 

3D fiber-deposition technique: In this method, the 

feedstock material is in a pellet or granule form that can 

be poured into the heated liquefier directly. Poly(ethylene 

glycol)-terephthalate-poly(butylenes terephthalate) 

(PEGT–PBT) block copolymer scaffolds have been 

fabricated for articulate tissue engineering applications 

[26]. Material flow is regulated by applying 

pressure to the syringe. 

PED: The extruder in this system is equipped with a 

built-in heating unit to melt the feedstock material, hence 

eliminating the need to produce precursor filaments. PCL 

scaffolds with a pore size of 250 mm were fabricated [27]. 

PEM: PLLA scaffolds with controllable porous 

architectures from 200 to 500 mm in size have been 

produced [28].

Table 1. Comparison of different rapid prototyping (RP) technologies applied in tissue engineering 

RP system Resolution (mm) Material Strength Weakness Refs 

Melt–dissolution deposition technique 

Fused deposition modeling 250 PCL a , PP-TCP, 

PCL-HA, PCL- 

TCP 

The melt process is generally undesirable from the 

perspective of scaffold bioactivity because of the elevated 

temperatures involved. This limitation drives researchers 

to replace the melting process with that of dissolution of 

materials. Systems developed include low-temperature 

deposition manufacturing (LDM) [29], multinozzle 

Good mechanical strength; 

versatile in lay-down pattern 

design 

High temperature; need to 

produce filament material; 

narrow processing window; 

rigid filament 

High temperature; 


3D fiber-deposition technique 250 PEGT-PBT Input material in pellet form; 

preparation time is reduced 

[26] 

Precision extruding depo- 250 PCL Input material in pellet form High temperature; 

[27] 

sition 


Precise extrusion 

200–500 PLLA-TCP Input material in pellet form High temperature; 

[28] 

manufacturing 


Low-temperature deposition 400 PLLA-TCP Can incorporate biomolecule Solvent is used; 

[29] 


requires freeze drying 

Multi-nozzle deposition 400 PLLA-TCP Enhanced range of materials Solvent is used; 

[30] 


can be used; can incorporate 

biomolecule 

requires freeze drying 

Pressure-assisted 

10–600 PCL, PLLA Enhanced range of materials Small nozzle inhibits 

[31] 

microsyringe 

can be used; can incorporate incorporation of particle; 

biomolecule; very fine resol- narrow range of printable 

ution can be achieved 

viscosities; solvent is used 

Robocasting 100–1000 Organic ink Enhanced range of materials Precise control of ink properties [34] 

can be used 

is crucial 

3D bioplotter 250 Hydrogel Enhanced range of materials Low mechanical strength; [35] 

can be used; can incorporate smooth surface; low accuracy; 

biomolecule 

slow processing; precise control 

of properties of material 

and medium; calibration for 

new material 

Rapid prototyping robotic 400–1000 Chitosanchito- Enhanced range of materials Precise control properties of [36] 

dispensing system 

san-HA 

can be used; can incorporate material and medium; requires 

Particle bonding techniques 

biomolecule 

freeze drying 

3-dimensional printinge 200 PLGA, starch- Microposity induced in the Material must be in powder [41] 

based polymer scaffold; enhanced range of form; limited mechanical 

materials can be used; water strength; Powdery surface 

used as binder; no support finish; trapped powder issue; 

structure needed; fast 

processing 

might require postprocessing 

TheriForme 300 PLLA Microposity induced in the Material must be in powder [45] 

scaffold; enhanced range of form; powdery surface finish; 

materials can be used; nonorganic 

binder is possible; no 

support structure is needed; 

fast processing 

trapped powder 

Selective laser sintering 500 PEEK-HA, PCL Microposity induced in the Material must be in powder [47] 

scaffold enhanced range of form; high temperature; 

materials can be used; 

powdery surface finish; 

Indirect RP fabrication method 

no support structure needed; 

fast processing 

trapped powder 

Melt deposition 250 Thermoplastic Enhanced range of materials Multisteps involved [48] 

polymer 

can be used; control of external 

and internal morphology 

Droplet deposition 180 Wax Enhanced range of materials 



Multisteps involved [49] 

Photo-polymerization 366 Resin Enhanced range of materials 



Multisteps involved [50] 

a 

Abbreviations: HA, hydroxyapatite; PCL, polycaprolactone; PEEK-HA, polyetheretherketone-hydroxyapatite; PEGT-PBT, poly(ethylene glycol)-terephthalate-poly(butylenes 

terephthalate; PLLA, poly-L-lactide; PP-TCP, polypropylene-tricalcium phosphate. 


Review TRENDS in Biotechnology Vol.22 No.12 December 2004 645 

[21] 

deposition manufacturing (MDM) [30], pressure-assisted 

microsyringes (PAM) [31] and robocasting [32]. 

LDM: The scaffold-building cycle is performed in a lowtemperature 

environment under 08C [29]. A PLLA–TCP 

pipe scaffold has been produced. 

MDM: This is an improved version of LDM, with the

646 

Figure 2. structure produced using fused deposition modeling. Uniformly 

interconnected square channels are obtained with a pattern setting of 08 or 908. 

The scaffold structure is highly regular and reproducible. The portion of the 

filament that spans across two supporting points is subjected to gravity-induced 

deformation during the solidification phase. Therefore, the setting of the machine 

parameters, as well as the material properties, must be precisely controlled to 

ensure minimum filament deflection. Filaments are aligned orthogonally, with 

grooves at the intersection point between consecutive layers. Cells on the scaffold 

must span across these grooves to cellularize the entire structure. 

advantage of being able to use a greater range of 

materials. The enhancement is achieved by incorporating 

more jetting nozzles into the system [29]. Support 

structures can be built using water, which is nontoxic 

and easy to remove. In the work by Zhuo et al. [30], 

biomolecules in the form of bone morphogenic protein 

were embedded in the bulk material and then released 

slowly as the scaffold degraded. 

PAM: A microsyringe is used to expel the dissolved 

polymer under low and constant pressure to form the 

desired pattern. The resolution of this method is on a 

cellular scale, which is remarkably high compared with 

the techniques described previously. Vozzi et al. [31] 

developed PCL and PLLA scaffolds with line width of 

20 mm. It has been demonstrated that the performance of 

this method is comparable to that of soft lithography [33]. 

However, capillaries with a very small diameter require 

careful handling to avoid any tip breakage. Higher 

pressure is also needed to expel the material from a 

small orifice. 

Robocasting: This patented system is able to lay down 

a highly concentrated, pseudoplastic-like colloidal suspension 

[32]. Therriault et al. [34] fabricated a 3D microvascular 

network by robocasting fugitive organic ink, 

followed by scaffold infiltration with epoxy resin and 

further postprocessing. 

In general, the scaffolds fabricated using the melt or 

solution deposition techniques described are usually 

meant to serve as hard-tissue scaffolds. Landers and 

Mülhaupt [35] have developed an aqueous system, the 3D 

bioplotter, to meet the demand for fabrication of hydrogel 

scaffolds useful in soft-tissue engineering. Hydrogels are 

becoming increasingly popular as a material for tissue 

engineering because of their high water content and the 

fact that they have similar mechanical properties to those 

of many soft tissues in the human body. Ang et al. [36] 



adopted a similar concept to develop a robotic dispenser, 

the rapid prototyping robotic dispensing system(RPBOD), 

for the fabrication of a chitosan scaffold. 

3D bioplotter: The key feature of this method is the 

3D dispensing of liquids and pastes into a liquid medium 

with matched density. The plotting material leaves the 

nozzle and solidifies in the plotting medium after bonding 

to the previous layer. The liquid medium compensates for 

gravity and hence no support structure is needed. 

Hydrogel scaffolds with well-defined internal pore 

structure were prepared by Landers et al. [37]. The 

hydrogel scaffolds had interconnected pores, 200–400 mm 

in diameter. However, the hydrogel presented a smooth 

surface, which might be nonadherent to cells [38]. Therefore, 

further surface coating was required to render the 

surface favorable for cell-adhesion. Fibroblasts seeded on 

the scaffolds showed almost complete coverage of cells. 

However, the scaffolds had limited resolution and mechanical 

strength. Material rigidity was shown to influence 

cell spreading and migration speed, as demonstrated by 

Wong et al. [39]. Cells displayed a preference for stiffer 

regions, and tended to migrate faster on surfaces with 

lower compliance. 

RPBOD: This system, developed by Ang et al. [36], 

consists of a computer-guided desktop robot and a onecomponent 

pneumatic dispenser. Material in liquid form 

was dispensed into a dispensing medium through a small 

Teflon-lined nozzle. Chitosan scaffolds with pore size of 

400–1000 mm were produced in the preliminary study. 

Particle-bonding techniques 

In particle-bonding techniques, particles are selectively 

bonded in a thin layer of powder material. The thin 2D 

layers are bonded one upon another to form a complex 3D 

solid object. During fabrication, the object is supported by 

and embedded in unprocessed powder. Therefore, this 

technique enables the fabrication of through channels and 

overhanging features. After completion of all layers, the 

object is removed from the bed of unbonded powder [20]. 

The powder utilized can be a pure powder or surfacecoated 

powder, depending on the application of the scaffold. 

It is possible to use a single one-component powder or a 

mixture of different powders, blended together. 

These techniques are capable of producing a porous 

structure with controllable macroporosity as well as 

microporosity. The microporosity arises from the space 

between the individual granules of powder. These techniques 

offer control over pore architecture by manipulating 

the region of bonding. However, the pore size is limited 

by the powder size of the stock material. Larger pores can 

be generated by mixing porogen into the powder bed 

before the bonding process. 

The powder-based materials provide a rough surface to 

the scaffold. It has been suggested that topographical cues 

might have a significant effect upon cellular behavior [40]. 

As a cell attaches to the scaffold, stretch receptors are 

activated. Receptors on the scaffold surface might be 

subjected to varying degrees of deformation, leading to 

activation of cell signal transduction pathways. Therefore, 

scaffolds fabricated via a particle-bonding technique

might be more advantageous in the context of cell 

attachment. 

Typical systems in this category include 3-DP [41], 

TheriForme [42] and SLS [43]. 

3DP: In this process, a stream of adhesive droplets is 

expelled through an inkjet printhead, selectively bonding 

a thin layer of powder particles to form a solid shape [20]. 

The resolution achieved is w300 mm. Kim et al. [44] 

employed 3DP using a particulate leaching technique to 

create porous scaffolds using polylactic-co-glycolic acid 

(PLGA) mix with salt particles and a suitable organic 

solvent. Pores formed were of the scale 45–150 mm with 

60% porosity. In vitro cell culture with hepatocytes showed 

ingrowth of these cells into the pore space. 

In an effort to render the system more biocompatible, 

Lam et al. [43] have formulated a blend of starch-based 

polymer powders that can be bonded together using 

distilled water. The group also tried to enhance the 

mechanical property of the scaffold produced by infiltrating 

the structure with PLLA and PCL copolymer solution. 

TheriForm: This system is similar to 3DP, in that a 

printhead assembly deposits binder droplets onto selected 

regions of the powder, swelling and dissolving the polymer 

powder in the printed regions. Zeltinger et al. [45] 

performed a study on a TheriForm-built PLLA scaffold 

with different pore sizes using canine dermal fibroblasts 

(DmFb), vascular smooth muscle cells (VSMC) and 

microvascular epithelial cells (MVEC). They found that 

DmFb is indifferent to pore size, whereas MVEC and 

VSMC favored a pore size of 90 mm and 107 mm, respectively, 

suggesting the existence of an optimal pore size for 

different cell types. 

SLS: This technique uses a deflected laser beam 

selectively to scan over the powder surface following the 

cross-sectional profiles carried by the slice data. The 

interaction of the laser beam with the powder elevates the 

powder temperature to reach the glass-transition 

temperature, causing surfaces in contact to deform 

and fuse together [20]. Thisisthepreferredfabrication 

process for producing complex porous ceramic matrices 

suitable for implantation in a bone defect, as demonstrated 

by Vail et al. [46]. 

The authors’ group has successfully sintered polyetheretherketone-hydroxyapatite 

(PEEK-HA) powder blends 

on a commercial SLS machine [47]. In the research, 

different weight percentage compositions of physically 

mixed PEEK-HA powder blends were sintered by varying 

the laser power and temperature settings (Figure 3). 

Indirect RP fabrication methods 

RP systems can also be utilized to produce a sacrificial 

mould to fabricate tissue-engineering scaffolds. These 

multistep methods usually involve casting of material in 

a mould and then removing or sacrificing the mould to 

obtain the final scaffold. Such techniques enable the user 

to control both the external and the internal morphology of 

the final construct. In addition, indirect methods also 

require less raw scaffold material while increasing the 

range of materials that can be used and making it possible 

to use composite blends that might require conflicting 

processing parameters. The original properties of the 



Figure 3. Micrographs of 90% polyetheretherketone by weight and 10% hydroxyapatite 

by weight sintered using selective laser sintering. The bonding between 

granules of particles is clearly observed, indicating the formation of microporosity 

within the structure. The surface topography of the powder is irregular and rough. 

biomaterial are well conserved because no heating process 

is imposed on the scaffold material. Common RP techniques 

employed include melt deposition [48], droplet 

deposition [49] and photopolymerization [50]. 

Melt deposition techniques 

The operating principle of these techniques, of which FDM 

is an example, is presented above. 

FDM: Bose et al. [48] produced alumina and b-TCP 

ceramic scaffolds with pore sizes in the range of 300–500 mm 

and porosity of 25–45%. The moulds were made using a 

standard thermoplastic polymer. Their research aimed to 

investigate the effect of pore size and porosity on the 

mechanical and biological responses. 

Droplet deposition technique 

This technique is based on inkjet printing technology. A 

stream of molten thermoplastic droplets is deposited on a 

working surface. Thermal energy in the deposited droplet 

causes local melting on the previous layer and solidifies as 

one piece. 

Droplet deposition is a complex interaction of droplet 

spreading upon impact, settling as a result of viscous and 

surface-tension forces, and a solidification process. A 

representative system is the ModelMakerIIe (MMII) [20]. 

MMII: This machine uses a single jet each for a plastic 

building material and a wax-like support material, which 

are held in a melted liquid state in reservoirs. The printer 

head ejects droplets of the materials as they are moved in 

X-Y fashion. After an entire layer of the object has 

hardened, a milling head is passed over the layer to 

ensure that a uniform thickness has been achieved. 

Taboas et al. [51] produced PLLA scaffolds with microand 

macroporosity for bone tissue engineering, in this case 

specifically trabecular bone. The global pores (500 mm 

wide channels) were computationally designed, whereas 

the local pores (50–100 mm wide voids) were formed by the 

porogen. PLA–PGA discrete composites were made using 

melt processing.

648 

MMII is selected by researchers to fabricate calcium 

phosphate scaffolds because the building material has a 

very low coefficient of thermal expansion. There will be 

minimal risk of fracture due to coefficient of thermal 

expansion mismatch with the ceramic during pyrolysis. 

Limpanuphap and Derby [52] fabricated TCP scaffolds 

with controlled internal porosity using a suspension of 

TCP in an acrylate binder. A similar route was used to 

produce a polymer–TCP scaffold, which is believed to show 

more potential for cell adhesion. Wilson et al. [53] 

fabricated HA scaffolds with a defined macroarchitecture. 

Channels achieved are w350–400 mm wide. These authors 

suggested that the inherent surface texture obtained from 

an MMII-built mould increased the surface area of the 

scaffold and led to a higher degree of calcium and phosphate 

release, which is advantageous to bone formation. 

Sachlos et al. [54] have successfully produced collagen 

scaffolds with predefined and reproducible internal channels. 

The smallest channel width achieved was reported to 

be as low as 135 mm. In a variation to Sachlos’ work, the 

authors have produced chitosan-collagen scaffolds. MMII 

moulds with intricate channels were built to contain a 

chitosan–collagen solution. The resultant gel-like scaffold 

was capable of attaining the designed morphology 

(Figure 4). These channels can serve as flow channels 

when coupled with a customized bioreactor, achieving 

more efficient perfusion of the culture medium. 

Photopolymerization techniques 

For photopolymerization techniques, optical energy is 

applied to irradiate the thin layer at the surface of a 

liquid photopolymer resin. The irradiation areas of 

resin react chemically and transform into a solid 

phase. A well-known photopolymerization technique is 

stereolithography (SLA) [20]. 

SLA: A UV laser traces out the first layer of photocurable 

resin, solidifying the model’s cross-section while 

leaving the remaining areas in liquid form. The elevator 

then drops by a sufficient amount to cover the solid 

polymer with another layer of liquid resin. A sweeper 

recoats the solidified layer with liquid resin and the laser 

traces the second layer atop the first. 

Chu et al. [50] have produced HA-based porous implants 

using SLA-built epoxy moulds. A thermal curable HA– 

acrylate suspension was cast into the mould to obtain a 

scaffold with interconnected channels. The resolution of 

channel width achieved was as low as 366 mm. 

In another study, investigators carried out an in vivo 

study using two different architecture designs, orthogonal 

Figure 4. Scaffold (right) produced using ModelMakerIIe-built mould (left). The 

scaffold is able to reproduce the predetermined morphology of the mould. The 

channels ensure high diffusion efficiency across the scaffold. 



and radial channels [55]. The preliminary results showed 

that controlling the overall geometry of the regenerated 

bone tissue was possible through the internal architectural 

design of the scaffolds. 

Challenges of RP in tissue engineering 

In spite of the increasing interest of tissue engineers in the 

use of RP, there are several challenges that need to be 

addressed, namely the limited range of materials, the 

optimal scaffold design, the bioactivity of the scaffold, as 

well as the issues of cell seeding and vascularization. Each 

of the issues will be discussed in detail. 

Range of materials 

Material processability: RP techniques are very 

specialized technologies in terms of material processability. 

Each technique requires a specific form of input 

material such as filament, powder, solid pellet or solution. 

Therefore, it must be ensured that the choice of materials 

for the scaffold is compatible with the selected RP process 

and that it can be efficiently produced in the form 

required. Other considerations during the selection of 

materials include the degradation profile and the mechanical 

strength of the scaffold. 

Degradation rate: In an ideal case, the scaffold should 

be remodeled and resorbed by growing cells and gradually 

replaced by the newly formed extracellular matrix and 

differentiated cells. A desirable feature would be synchronization 

of the polymer degradation rate with the rate of 

tissue ingrowth. Therefore, the degradation properties of a 

scaffold are of crucial importance for the success of the 

scaffold-based approach. 

The degradation–absorption mechanism is the result of 

many interrelated factors, including the hydrophilicity of 

the polymer backbone, degree of crystallinity, presence 

of catalysts, volume of porosity and the surface area. 

Balancing each of these factors will enable an implant to 

degrade slowly and transfer stress at an appropriate rate 

to the surrounding tissues as they heal. This is one of the 

major challenges facing tissue engineering research today. 

Degradation product: Even though degradation 

products of biodegradable polymers are known to be 

largely non-cytotoxic, little information is available 

regarding the degradation rate-dependent acidic byproduct 

effect of the scaffold. Sunga et al. [56] found that fast 

degradation of the polymer negatively affects cell viability 

and migration into the scaffold, both in vitro and in vivo. 

This can be explained by the rapid local acidification due 

to polymer degradation. Therefore, a more systematic 

investigative approach is needed to classify the material 

degradation profile. 

Mechanical strength of scaffolds: Cells are able to 

detect with high sensitivity the mechanical properties of 

the adhesion substrate, and to regulate integrin binding 

and the assembly of focal adhesion plaques and the 

cytoskeleton accordingly [57]. If the adhesion substrate 

is too rigid and nondeformable, the cells are not able to 

reorganize and recruit the receptors into focal adhesion 

plaques, which is a prerequisite for the delivery of signals, 

ensuring the viability of anchorage-dependent cells. 

Similarly, if the material is too compliant, it does not

enable the anchorage of cells, owing to the inability to 

resist the tractional forces generated by the assembling 

cytoskeleton. 

Scaffold architecture design 

Pore size: The diverse nature of tissues requires 

different optimal pore size for different types of tissue. 

Despite numerous proof-of-concept studies exhibiting the 

existence of an optimal range of pore size for different cell 

types [58–60], little is known about specific optimal pore 

sizes for particular types of cell. Therefore, the pore size 

selected is governed by general empirical guidelines. 

Scaffold morphology: RP-fabricated scaffolds generally 

present many edges and grooves. The effect of these 

discontinuities in topography might affect the adhesion 

and migration of cells, as shown by Yin’s work. Yin et al. 

[61] grew cardiac cells on microgrooved elastic scaffolds to 

investigate the topography-driven changes in cardiac 

electromechanics. The grooves are 50 mm in depth and 

120 mm in width. These authors demonstrated a direct 

influence of the microstructure on cardiac function and 

susceptibility to arrhythmias via calcium-dependent 

mechanisms. 

Surface topography: The surface roughness of the 

scaffold is important in cell–matrix interactions. The 

rough powder surface produced from powder-based RP 

techniques might enhance cell adhesion. However, if the 

surface is too rough, the cells adhering to these materials 

might not be able to develop distinct focal adhesion 

plaques or bridge the irregularities. Moreover, the sharpness 

of the surface could damage the cell physically. In 

certain RP systems, such as FDM and bioplotter, the 

smooth surface of solidified materials cannot ensure firm 

cell adhesion and therefore require further surface 

modification or coating. 

Bioactivity of RP-fabricated scaffolds 

The interaction of cells with the scaffold is governed by 

both structural and chemical signaling molecules that 

have a decisive role for cell adhesion and the further 

behavior of cells after initial contact [62]. 

The extent of initial cell adhesion decides the number, 

size, shape and distribution of focal adhesion plaques 

formed on the cell membrane, which subsequently 

describes the size and shape of the cell-spreading area. 

The extent of spreading is crucial for further migratory, 

proliferation and differentiation behavior of anchoragedependent 

cells. 

Current strategies to control the proliferation and other 

behaviors of cells on advanced biospecific materials 

involve patterning the material surfaces with adhesive 

molecules or by incorporating a controlled release of 

biomolecules, such as natural growth factors, hormones, 

enzymes or synthetic cell cycle regulators. 

Some RP systems that have excluded high-temperature 

operation, such as MDM and bioplotter, offer the opportunity 

of incorporating the biomolecule during the building 

cycle. However, further information, such as the type 

of biomolecule, the optimal concentration and spatial 

control of these biomolecules, is needed to produce the 

most favorable scaffold. 



Cell seeding and vascularization 

One significant challenge in the scaffold-based approach 

in tissue engineering is to distribute a high density of cells 

efficiently and uniformly throughout the scaffold volume. 

The only Food and Drug Administration-approved cell 

seeding process involves the use of a Petri dish. However, 

this method has been shown to fail to deliver cells deep 

inside the scaffold with uniform distribution [63–65]. 

Therefore, the cellularization of a 3D scaffold is closely 

related to the advances of bioreactor technologies. 

Bioreactors are generally defined as devices in which 

biological and/or biochemical processes develop under 

closely monitored and tightly controlled operating conditions 

[66]. Types of bioreactor include the spinner flask, 

perfusion cartridge and rotary cell culture system [67]. 

Each of the systems utilizes different physical principles 

and might necessitate specific design considerations in 

terms of scaffold shape and strength. 

RP systems present great flexibility in scaffold design 

and development. RP-fabricated scaffolds can be designed 

to have interconnected flow channels to fit into the 

operation of the bioreactor, as displayed by the work of 

Sakai et al. [68]. 

Sufficient vascularization of the scaffold, to maintain 

adequate perfusion, is a primary consideration in the 

engineering of large tissue constructs. Rapid and high 

levels of vascularization of the cell-seeded scaffold are 

essential to meet the challenge. One possible approach to 

achieve vascularization is by incorporating a growth 

factor into the scaffold. Several angiogenic factors, such 

as vascular endothelial growth factor, fibroblast growth 

factor, epidermal growth factor, platelet-derived growth 

factors and transforming growth factors, have been 

identified, and these promote the formation of new 

vascular beds from endothelial cells present within tissues 

[69]. Sheridan et al. [70] considered that the localization 

and controlled release of these factors from a matrix might 

bring about enhanced vascularization of engineered 

tissues. 

An alternative approach to enhance the rate of 

vascularization is to transplant endothelial cells onto the 

scaffold [71]. Experimental studies with rats have confirmed 

that the vascularization of matrices is accelerated 

with endothelial cell transplantation. The bioactivity of 

the scaffold has a crucial role in this approach. 

The RP fabrication method offers the flexibility and 

capability to couple the design and development of a 

bioactive scaffold with the advances of cell-seeding 

technologies, to enhance the success of scaffold-based 

tissue engineering. 

New development: automation and direct organ 

fabrication 

Automated design, development and characterization: 

RP has the potential of automating the design and 

fabrication of patient-specific scaffolds. In the work of 

Cheah et al. [72], computer-aided design (CAD) data 

manipulation techniques were utilized to develop a 

program algorithm that can be used to design scaffold 

internal architectures from a selection of open-celled 

polyhedral shapes. The automated scaffold assembly

650 

algorithm can be interfaced with various RP technologies, 

to achieve automated production of scaffolds. 

Because RP processes offer complete user control in 

terms of the structural features of the scaffold, it is 

therefore possible to characterize the scaffold using an 

automated algorithm. A computer-aided characterization 

approach can be applied to predict the effective mechanical 

properties of scaffolds and also to investigate the effect 

of design and process parameters on the structural 

properties of the scaffolds. Fang et al. [73] characterized 

the effective mechanical properties of porous PCL scaffolds 

manufactured by PED using a computational algorithm 

for finite element implementation and numerical solution 

of asymptotic homogenization theory. 

The ease of scaffold fabrication using RP provides a 

straightforward way to study the cell–matrix interaction. 

The effects of material rigidity, surface topography and 

roughness, pore size and architecture can be investigated 

independently to gain more insight into cell behavior. 

Recent studies have displayed a new school of thought, 

using the concept of layered manufacturing techniques to 

produce an organ directly. These new technologies include 

organ printing [74–76], laser printing of cells [77], 

photopatterning of hydrogel [78] and microfluidics technology 

[79]. 

Organ printing: Boland et al. [76] developed a cell 

printer to implement the technology. The device is capable 

of printing single cells, cell aggregates and the supportive 

thermoreversible gel that serves as ‘printing paper’. These 

authors demonstrated the feasibility of this technique by 

printing a tubular collagen gel with bovine aortal 

endothelial cells. 

Laser printing of cells: A laser-based printer, termed 

matrix-assisted pulsed laser evaporation direct write 

(MAPLE DW), was used to deposit micron-scale patterns 

of pluripotent embryonic carcinoma cells onto thin layers 

of hydrogel [77]. A cell viability of 95% was reported. 

Photopatterning of hydrogels: Valerie and Sangeeta 

[78] adapted photolithographic techniques from the silicon 

chip industry. The process starts with filling a Teflon base 

with a thin layer of polymer solution loaded with cells. UV 

light is shone through a patterned template atop the thin 

film, curing the exposed polymer that sets with cells 

inside. Complex 3D structures, containing regions of 

different cells, can be built by using different templates 

and adding layers atop each other. 

Microfluidics technology: Tan and Desai [79] 

reported a layer-by-layer microfluidic method to build a 

3D heterogeneous multiplayer tissue-like structure inside 

microchannels. This approach extends the 2D cell patterning 

technique into the vertical axis, involving immobilization 

of a cell–matrix assembly, cell–matrix 

contraction and pressure-driven microfluidic delivery 

processes. 

Conclusion 

The emergence of various different approaches in tissue 

engineering, ranging from a scaffold-based approach to 

scaffold-free layer-by-layer manufacturing technique, has 

highlighted the fact that the field of tissue engineering is 

still growing. Looking towards the future, RP technologies 



hold great potential in the context of scaffold fabrication. 

This technology enables the tissue engineer to have full 

control over the design, fabrication and modeling of the 

scaffold being constructed, providing a systematic learning 

channel for investigating cell–matrix interactions. 

Additionally, indirect RP methods, coupled with conventional 

pore-forming techniques, further expand the range 

of materials that can be used in tissue engineering. 

Inspired by the additive nature of layered manufacturing, 

the layer-by-layer fabrication method underlines the 

future development of tissue engineering. Further development 

and advances in RP in tissue engineering require 

the design of new materials, optimal scaffold design and 

the input of enhanced knowledge of cell physiology, 

including optimal cell seeding and vascularization, so as 

to enable the tissue engineer to lay down more specific 

design requirements. Nevertheless, RP is a promising 

candidate, serving as a methodical interface between 

tissue and engineering. 

References 

1 Langer, R. and Vacanti, J. (1993) Tissue engineering. Science 260, 

920–926 

2 Sonal, L. et al. (2001) Tissue engineering and its potential impact on 

surgery. World J. Surg. 25, 1458–1466 

3 Jennifer, J.M. et al. (1998) Transplantation of cells in matrices for 

tissue regeneration. Adv. Drug Deliv. Rev. 33, 165–182 

4 Kim, B.S. et al. (2001) Development of biocompatible synthetic 

extracellular matrices for tissue engineering. Trends Biotechnol. 16, 

224–230 

5 Leong, K.F. et al. (2003) Solid freeform fabrication of three-dimensional 

scaffolds for engineering replacement tissues and organs. 

Biomaterials 24, 2363–2378 

6 Mikos, A.G. et al. (1994) Preparation and characterization of poly 

(L-lactic acid) foam. Polymer 35, 1068–1077 

7 Mooney, D.J. et al. (1996) Novel approach to fabricate porous sponge of 

poly(D,L-lactic-co-glycolic acid) without the use of organic solvents. 


8 Freed, L.E. et al. (1994) Biodegradable polymer scaffolds for tissue 

engineering. Biotechnology (N. Y.) 12, 689–693 

9 Lo, H. et al. (1995) Fabrication of controlled release biodegradable 

foams by phase separation. Tissue Eng. 1, 15–28 

10 Thomson, J.I. et al. (1995) Fabrication of biodegradable polymer 

scaffolds to engineering trabecular bone. J. Biomater. Sci. Polym. Ed. 

7, 23–28 

11 Whang, K. et al. (1995) A novel method to fabricate bioabsorbable 

scaffolds. Polym. 36, 837 

12 Hsu, Y.Y. et al. (1997) Effect of polymer foam morphology and density 

on kinetics of in vitro controlled release of ionized from compressed 

foam matrices. J. Biomed Mater Sci 35, 107–116 

13 Kim, B.S. and Mooney, D.J. (1998) Engineering smooth muscle tissue 

with a predefined structure. J. Biomed. Mater. Res. 41, 322–332 

14 Ho, M.H. et al. (2004) Preparation of porous scaffolds by using freezeextraction 

and freeze-gelation methods. Biomaterials 25, 129–138 

15 Murphy, W.L. et al. (2002) Salt fusion: an approach to improve pore 

interconnectivity within tissue engineering scaffold. Tissue Eng. 8, 

43–52 

16 Chen, V.J. and Ma, P.X. (2004) Nano-fibrous poly(L-lactic acid) 

scaffolds with interconnected spherical macropores. Biomaterials 25, 

2065–2073 

17 Gross, K.A. and Rodríguez-Lorenzo, L.M. (2004) Biodegradable 

composite scaffolds with an interconnected spherical network for 

bone tissue engineering. Biomaterials 25, 4955–4962 

18 Yang, S. et al. (2001) The design of scaffolds for use in tissue 

engineering. Part I. Traditional factors. Tissue Eng. 7, 679–689 

19 Yang, S. et al. (2002) The design of scaffolds for use in tissue 

engineering. Part II. Rapid prototyping techniques. Tissue Eng. 8, 

1–11

20 Chua, C.K. et al. (2003) Rapid Prototyping Principles and Applications, 

World Scientific 

21 Zein, I. et al. (2002) Fused deposition modeling of novel scaffold 

architectures for tissue engineering applications. Biomaterials 23, 

1169–1185 

22 Samar, J.K. et al. (2003) Development of controlled porosity polymerceramic 

composite scaffolds via fused deposition modeling. Mater Sci 

Eng C23, 611–620 

23 Ramakrishma, S. et al. (2001) Biomedical applications of polymercomposite 

materials: a review. Compos. Sci. Technol. 61, 1189–1224 

24 Endres, M. et al. (2003) Osteogenic induction of human bone marrowderived 

mesenchymal progenitor cells in novel synthetic polymerhydrogel 

matrices. Tissue Eng. 9, 689–702 

25 Tienen, T.G.V. et al. (2002) Tissue ingrowth and degradation of two 

biodegradable porous polymers with different porosities and pore size. 


26 Woodfield, T.B.G. et al. (2004) Design of porous scaffolds for cartilage 

tissue engineering using a three-dimensional fiber-deposition technique. 


27 Wang, F. et al. (2004) Precision extruding deposition and characterization 

of cellular poly-3-Caprolactone tissue scaffolds. Rapid Prototyping 

J 10, 42–49 

28 Zhuo, X. et al. (2001) Fabrication of porous poly(L-lactic acid) scaffolds 

for born tissue engineering via precise extrusion. Scripta Mater. 45, 

773–779 

29 Zhuo, X. et al. (2002) Fabrication of porous scaffolds for bone tissue 

engineering via low-temperature deposition. Scripta Mater. 46, 

771–776 

30 Zhuo, X. et al. (2003) Layered manufacturing of tissue engineering 

scaffolds via multi-nozzle deposition. Mater. Lett. 57, 2623–2628 

31 Vozzi, G. et al. (2002) Microsyringe-based deposition of two-dimensional 

and three-dimensional polymer scaffolds with a well-defined 

geometry for application to tissue engineering. Tissue Eng. 8, 

1089–1098 

32 Cesarano, J. and Calvert, P. (2000) Freeforming objects with lowbinder 

slurry. US Patent 6,027,326 

33 Vozzi, G. et al. (2003) Fabrication of PLGA scaffolds using soft 

lithography and microsyringe deposition. Biomaterials 24, 2533–2540 

34 Therriault, D. et al. (2003) Chaotic mixing in three-dimensional 

microvascular networks fabricated by direct-write assembly. Nat. 

Mater. 2, 265–271 

35 Landers, R. and Mülhaupt, R. (2000) Desktop manufacturing of 

complex objects, prototypes and biomedical scaffolds by means of 

computer-assisted design combined with computer-guided 3D plotting 

of polymers and reactive oligomers. Macromol. Mater. Eng. 282, 17–21 

36 Ang, T.H. et al. (2002) Fabrication of 3D chitosan-hydroxyapatite 

scaffolds using a robotic dispensing system. Mater. Sci. Eng. C 20, 

35–42 

37 Landers, R. et al. (2002) Fabrication of soft tissue engineering 

scaffolds by means of rapid prototyping techniques. J. Mater. Sci. 37, 

3107–3116 

38 Landers, R. et al. (2002) Rapid prototyping of scaffolds derived from 

thermoreversible hydrogels and tailored for applications in tissue 

engineering. Biomaterials 23, 4437–4447 

39 Wong, J.Y. et al. (2003) Directed movement of vascular smooth muscle 

cells on gradient-compliant hydrogels. Langmuir 19, 1908–1913 

40 Flemming, R.G. et al. (1999) Effects of synthetic micro- and nanostructured 

surfaces on cell behavior. Biomaterials 20, 573–588 

41 Lam, C.X.F. et al. (2002) Scaffold development using 3D printing with 

a starch-based polymer. Mater. Sci. Eng. C 20, 49–56 

42 Griffith, L.G. and Naughton, G. (2002) Tissue engineering – current 

challenges and expanding opportunities. Science 298, 1009–1014 

43 Calvert, J.W. and Weiss, L. (2001) Assembled scaffolds for threedimensional 

cell culturing and tissue regeneration. US Patent 

6,143,293 

44 Kim, S.S. et al. (1998) Survival and function of hepatocytes on a novel 

three-dimensional synthetic biodegradable polymeric scaffold with an 

intrinsic network of channels. Ann. Surg. 228, 8–13 

45 Zeltinger, J. et al. (2001) Effect of pore size and void fraction on cellular 

adhesion, proliferation and matrix deposition. Tissue Eng. 7, 557–572 

46 Vail, N.K. et al. (1999) Materials for biomedical applications. Mater. 

Des. 20, 123–132 



47 Tan, K.H. et al. (2003) Scaffold development using selective laser 

sintering of polyetheretherketone-hydroxyapatite biocomposite 

blends. Biomaterials 24, 3115–3123 

48 Bose, S. et al. (2003) Pore size and pore volume effects on alumina and 

TCP ceramic scaffolds. Mater. Sci. Eng. C 23, 479–486 

49 Sachlos, E. and Czernuska, J.T. (2003) Making tissue engineering 

scaffolds work. Review on the application of solid freeform fabrication 

technology to the production of tissue engineering scaffolds. Eur Cell 

Mater 5, 29–40 

50 Chu, T.M.G. et al. (2001) Hydroxyapatite implants with designed 

internal architecture. J. Mater. Sci. Mater. Med. 12, 471–478 

51 Taboas, J.M. et al. (2003) Indirect SFF fabrication of local and global 

porous, biomimetic and composite 3D polymer-ceramic scaffolds. 


52 Limpanuphap, S. and Derby, B. (2002) Manufacture of biomaterials by 

a novel printing process. J. Mater. Sci. Mater. Med. 13, 1163–1166 

53 Wilson, C.E. et al. (2004) Design and fabrication of standardized 

hydroxyapatite scaffolds with a defined macro-architecture by rapid 

prototyping for bone-tissue-engineering research. J. Biomed. Mater. 

Res. 68A, 123–132 

54 Sachlos, E. et al. (2003) Novel collagen scaffolds with predefined 

internal morphology made by solid freeform fabrication. Biomaterials 

24, 1487–1497 

55 Chu, T.M.G. et al. (2002) Mechanical and in vivo performance of 

hydroxyapatite implants with controlled architectures. Biomaterials 

23, 1283–1293 

56 Sung, H. et al. (2004) The effect of scaffold degradation rate on threedimensional 

cell growth and angiogenesis. Biomaterials 25, 

5735–5742 

57 Wang, N. et al. (2001) Mechanical behavior in living cells consistent 

with the tensegrity model. Proc. Natl. Acad. Sci. U. S. A. 98, 

7765–7770 

58 Ranucci, C.S. et al. (2000) Control of hepatocyte function on collagen 

foams: sizing matrix pores for selective induction of 2-D and 3-D 

morphogenesis. Biomaterials 21, 783–793 

59 Dalton, B.A. et al. (1999) Modulation of corneal epithelial stratification 

by polymer surface topography. J. Biomed. Mater. Res. 45, 

384–394 

60 Bignon, A. et al. (2003) Effect of micro- and macroporosity of bone 

substitutes on their mechanical properties and cellular response. 

J. Mater. Sci. Mater. Med. 14, 1089–1097 

61 Yin, L. et al. (2004) Scaffold topography alters intracellular calcium 

dynamics in cultured cardiomyocyte networks. Am. J. Physiol. Heart 

Circ. Physiol. 287, H1276–H1285 

62 Bacakova, L. et al. (2004) Cell adhesion on artificial materials for 

tissue engineering. Physiol. Res. 53, S35–S45 

63 Li, Y. et al. (2001) Effects of filtration seeding on cell density, spatial 

distribution, and proliferation in nonwoven fibrous matrices. Biotechnol. 

Prog. 17, 935–944 

64 Xiao, Y.L. et al. (1999) Static and dynamic fibroblast seeding and 

cultivation in porous PEO/PBT scaffolds. J. Mater. Sci. Mater. Med. 10, 

773–777 

65 Kim, B.S. et al. (1998) Optimizing seeding and culture methods to 

engineer smooth muscle tissue on biodegradable polymer matrices. 

Biotechnol. Bioeng. 57, 46–54 

66 Martin, I. et al. (2004) The role of bioreactors in tissue engineering. 

Trends Biotechnol. 22, 80–86 

67 Goldstein, A.S. et al. (2001) Effect of convection on osteoblastic cell 

growth and function in biodegradable polymer foam scaffolds. 


68 Sakai, Y. et al. (2004) A novel poly-L-lactic acid scaffold that possesses 

a macroporous structure and a branching/joining three-dimensional 

flow channel network: its fabrication and application to perfusion 

culture of human hepatoma Hep G2 cells. Mater. Sci. Eng. C 24, 

379–386 

69 Bouhadir, K.H. and Mooney, D.J. (2001) Promoting angiogenesis in 

engineered tissues. J. Drug Target. 9, 397–406 

70 Sheridan, M.H. et al. (2000) Bioabsorbable polymer scaffolds for tissue 

engineering capable of sustained growth factor delivery. J. Control. 

Release 64, 91–102 

71 Holder, W.D. et al. (1997) Increased vascularization and heterogeneity 

of vascular structures occurring in polyglycolide matrices containing 

aortic endothelial cells implanted in the rat. Tissue Eng. 3, 149–160

652 


72 Cheah, C.M. et al. (2004) Automatic algorithm for generating complex 

polyhedral scaffold structures for tissue engineering. Tissue Eng. 10, 

595–610 

73 Fang, Z. et al. Computer-aided characterization for effective mechanical 

properties of porous tissue scaffolds. Comput Aided Design Article 

(in press) 

74 Mironov, V. et al. (2003) Organ printing: computer-aided jet-based 3D 

tissue engineering. Trends Biotechnol. 21, 157–161 

75 Wilson, W.C. and Boland, T. (2003) Cell and organ printing 1: protein 

and cell printers. Anat. Rec. 272A, 491–496 

Endeavour 

the quarterly magazine for the history 

and philosophy of science 

You can access Endeavour online via 

ScienceDirect, where you’ll find a 

collection of beautifully illustrated 

articles on the history of science, book 

reviews and editorial comment. 

Featuring 

76 Boland, T. et al. (2003) Cell and organ printing 2: fusion of cells 

aggregates in three-dimensional gels. Anat. Rec. 272A, 497–502 

77 Ringeisen, R.B. et al. (2004) Laser printing of pluripotent embryonal 

carcinoma cells. Tissue Eng. 10, 483–491 

78 Valerie, A.L. and Sangeeta, N.B. (2002) Three-dimensional photopatterning 

of hydrogels containing living cells. Biomed Microdevices 

4, 257–266 

79 Tan, W. and Desai, T.A. (2004) Layer-by-layer microfluidics for 

biomemitic three-dimensional structures. Biomaterials 25, 

1355–1364 

Sverre Petterssen and the Contentious (and Momentous) Weather Forecasts for D-Day, 6 June 1944 by J.R. Fleming 

Food of Paradise: Tahitian breadfruit and the Autocritique of European Consumption by P. White and E.C. Spary 

Two Approaches to Etiology: The Debate Over Smoking and Lung Cancer in the 1950s by M. Parascandola 

Sicily, or sea of tranquility? Mapping and naming the moon by J. Vertesi 

The Prehistory of the Periodic Table by D. Rouvray 

Two portraits of Edmond Halley by P. Fara 

and coming soon 

Fighting the ‘microbe of sporting mania’: Australian science and Antarctic exploration in the early twentieth century 

by P. Roberts 

Learning from Education to Communicate Science as a Good Story by A. Negrete and C. Lartigue 

The Traffic and Display of Body Parts in the Early-19th Century by S. Alberti and S. Chaplin 

The Rise, Fall and Resurrection of Group Selection by M. Borrello 

Pomet’s great ‘‘Compleat History of Drugs’’ by S. Sherman 

Sherlock Holmes: scientific detective by L. Snyder 

The Future of Electricity in 1892 by G.J.N. Gooday 

The First Personal Computer by J. November 

Baloonmania: news in the air by M.G. Kim 


and much, much more . . . 

Locate Endeavour on ScienceDirect (http://www.sciencedirect.com)

Rapid prototyping in tissue engineering: challenges and potential

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?