Solvent-free polymer/bioceramic scaffolds for bone tissue engineering: fabrication,analysis, and cell growth

This study examines the potential use of porous polycaprolactone (PCL) and polycaprolocatone/hydroxyapatite (PCL/HA) scaffolds fabricated through melt molding and porogen leaching for bone tissue engineering. While eliminating organic solvents is desirable, the process steps proposed in this study for uniformly dispersing HA particles (~5?μm in size) within the scaffold can also contribute to homogeneous properties for these porous composites. Poly(ethylene oxide) (PEO) was chosen as a porogen due to its similar density and melting point as PCL. Pore size of the scaffold was controlled by limiting the size of PCL and PEO particles used in fabrication. The percent of HA in the fabricated scaffolds was quantified by thermogravimetric analysis (TGA). Mechanical testing was used to compare the modulus of the scaffolds to that of bone, and the pore size distribution was examined with microcomputed tomography (μCT). Scanning electron microscopy (SEM) was used to examine the effect on scaffold morphology caused by the addition of HA particles. Both μCT and SEM results showed that HA could be incorporated into PCL scaffolds without negatively affecting scaffold morphology or pore formation. Energy-dispersive X-ray spectroscopy (EDS) and elemental mapping demonstrated a uniform distribution of HA within PCL/HA scaffolds. Murine calvaria-derived MC3T3-E1 cells were used to determine whether cells could attach on scaffolds and grow for up to 21 days. SEM images revealed an increase in cell attachment with the incorporation of HA into the scaffolds. Similarly, DNA content analysis showed a higher cell adhesion to PCL/HA scaffolds.     

Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering

Nerve tissue engineering is one of the most promising methods to restore nerve systems in human health care. Scaffold design has pivotal role in nerve tissue engineering. Polymer blending is one of the most effective methods for providing new, desirable biocomposites for tissue-engineering applications. Random and aligned PCL/gelatin biocomposite scaffolds were fabricated by varying the ratios of PCL and gelatin concentrations. Chemical and mechanical properties of PCL/gelatin nanofibrous scaffolds were measured by FTIR, porometry, contact angle and tensile measurements, while the in vitro biodegradability of the different nanofibrous scaffolds were evaluated too. PCL/gelatin 70:30 nanofiber was found to exhibit the most balanced properties to meet all the required specifications for nerve tissue and was used for in vitro culture of nerve stem cells (C17.2 cells). MTS assay and SEM results showed that the biocomposite of PCL/gelatin 70:30 nanofibrous scaffolds enhanced the nerve differentiation and proliferation compared to PCL nanofibrous scaffolds and acted as a positive cue to support neurite outgrowth. It was found that the direction of nerve cell elongation and neurite outgrowth on aligned nanofibrous scaffolds is parallel to the direction of fibers. PCL/gelatin 70:30 nanofibrous scaffolds proved to be a promising biomaterial suitable for nerve regeneration.     

Effect of porosity and pore size on microstructures and mechanical properties of poly-epsilon-caprolactone- hydroxyapatite composites

The influence of variant pore-size and porosity on the microstructure and the mechanical properties of poly-epsilon-caprolactone (PCL) and hydroxyapatite (HA) composite were examined for an optimal scaffold in bone tissue engineering. Three various amounts of sodium chloride (NaCl, as porogens) with two distinct particle size ranges (212-355 mum and 355-600 mum) were blended into PCL and HA mixture, followed by a leaching technique to generate PCL-HA scaffolds with various pores and porosity. The porosities of the scaffolds were correlated with the porogen size and concentration. The morphological properties of the resulting scaffolds were assessed by micro-computerized tomography (muCT), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Extensive PCL-HA pore interconnections with thinner pore walls were present in scaffolds with higher concentration (4:1 w/w) and larger particulate of porogen used in the fabrication process. Embedding of HA particles in the scaffold resulted in rough surfaces on the composites. Instron actuator testing indicated that the tensile strengths and Young's moduli of scaffolds were influenced by both the porosities and pore sizes of the scaffold. It was apparent that increasing the concentration of porogen compromised the mechanical properties; and a larger porogen particle size led to increased tensile strength but a reduction in Young's modulus. Overall, the data indicated that modification of the concentration and particle size of porogen altered the porous features and mechanical strength of HA-PCL scaffolds. This provided means to manipulate the properties of biocompatible cell-supporting scaffolds for use as bone graft substitutes.     

Porous polycaprolactone/nanohydroxyapatite tissue engineering scaffolds fabricated by combining NaCl and PEG as co-porogens: structure, property, and chondrocyte-scaffold interaction in vitro

In this study, porous polycaprolactone/nanohydroxyapatite (PCL/nHA) composite scaffolds were fabricated using a modified melt-molding/leaching technique, by the combination of salt particulate (NaCl) and water-soluble polymer (PEG) as co-porogens. The porogens were kept at a constant proportion of 70% in the blends but varied in the NaCl/PEG ratio and the PEG variety to generate PCL/nHA scaffolds with various pore architectures. The resultant composite scaffolds were investigated on their morphologies, physicochemical properties, mechanical properties, and in vitro degradation. The cell-scaffold interactions were evaluated in vitro using chondrocyte. Generally, the PCL/nHA scaffolds exhibited multimodal pore morphologies consisting of macropores and interconnected micropores, created by the extraction of NaCl particulate and continuous PEG phase. The evolution of porogens led to much effect on the overall pore architecture of the scaffolds; subsequently, their physiochemical and mechanical properties and degradation behaviors, as well as the cell binding and proliferation. The PCL/nHA scaffold prepared from NaCl/PEG 4000 (20/50) presented more macropores (>50 μm) with interconnectivity and showed higher strength and improved bioactivity than the others. All of these results suggest promising potentials of PCL/nHA scaffolds developed in this study desired for cartilage tissue engineering.     

A combined compression molding,heating, and leaching process for fabrication of micro-porous poly(ε-caprolactone) scaffolds

Abstract

Biomaterial scaffolds have been increasingly used for tissue engineering applications as well as three dimensional (3D) cell culture models. Herein, we report a simple procedure combining compression molding, heating, and leaching methods for the fabrication of 3D micro-porous poly(ε-caprolactone) (PCL) biomaterial scaffolds. In this procedure, PCL micro particles are mixed with NaCl of defined sizes and compression molded, followed by heating and subsequent leaching of NaCl particles. This technique eliminates the gas foaming method, which is commonly used in the fabrication of PCL scaffolds. Process and scaffold parameters (i.e., heating time, NaCl concentration, and NaCl particle size) were varied and analyzed to determine their impact on the overall scaffold structural and mechanical properties. An increase in NaCl particle size led to an increase in pore area but did not significantly impact the mechanical properties of the scaffolds. Additionally, NaCl concentration did not show a significant effect on pore area, but considerably impacted the mechanical properties, water absorption capacity and porosity of the scaffolds. Variations in the heating time did not have an effect in the pore area, porosity, water absorption capacity or mechanical properties of the scaffolds. We also demonstrated the ability of these scaffolds to support the proliferation of breast cancer cells. Overall, these results elucidated structure-property relationships in the fabricated micro-porous PCL scaffolds. Further, this procedure could be potentially scaled up for the fabrication of micro-porous PCL scaffolds.     

In vitro evaluation of random and aligned polycaprolactone/gelatin fibers via electrospinning for bone tissue engineering

Scaffold, as an essential element of tissue engineering, should provide proper chemical and structural cues to direct tissue regeneration. In this study, aligned and random polycaprolactone (PCL)/gelatin fibrous scaffolds with different mass ratio were electrospun. Chemical, structural, and mechanical properties of PCL/gelatin fibrous scaffolds were characterized by FTIR and tensile measurements. The average diameters of different groups were between 334.96?±?41.43?nm and 363.78?±?50.49?nm. Blending PCL with gelatin increased the mechanical properties of the scaffolds. The cell culture results demonstrated that the mass ratio of PCL and gelatin showed no obvious effects on cell behavior, whereas the cell growth behavior was affected by the fibers orientation. Higher elongation ratio, enhanced cell proliferation and elevated alkaline phosphatase activity were observed for cells cultured on aligned fibers. The findings in our research provide insightful information for the design and fabrication of scaffolds for bone tissue engineering.     

Fabrication and characterization of novel nano- and micro-HA/PCL composite scaffolds using a modified rapid prototyping process

Novel three-dimensional scaffolds consisting of nano- and microsized hydroxyapatite (HA)/poly(epsilon-caprolactone) (PCL) composite were fabricated using a modified rapid-prototyping (RP) technique for bone tissue engineering applications. The size of the nano-HA ranged from 20 to 90 nm, whereas that of the micro-HA ranged from 20 to 80 microm. The scaffold macropores were well interconnected, with a porosity of 72-73% and a pore size of 500 microm. The compressive modulus of the nano-HA/PCL and micro-HA/PCL scaffolds was 3.187 +/- 0.06 and 1.345 +/- 0.05 MPa, respectively. The higher modulus of the nano-HA/PCL composite (n-HPC) was to be likely caused by a dispersion strengthening effect. The attachment and proliferation of MG-63 cells on n-HPC were better than that on the micro-HA/PCL composite (m-HPC) scaffold. The n-HPC was more hydrophilic than the m-HPC because of the greater surface area of HA exposed to the scaffold surface. This may give rise to better cell attachment and proliferation. Bioactive n-HA/PCL composite scaffold prepared using a modified RP technique has a potential application in bone tissue engineering.     

Three dimensionally printed pearl powder/poly-caprolactone composite scaffolds for bone regeneration**

Abstract

Pearl has great potential as a natural biomaterial for bone tissue engineering, but it suffers from low porosity, difficulty in molding, and poor anti-buckling property. In this study, we used the 3-D printing technique to fabricate original pearl powder and PCL composite scaffolds with different concentrations of pearl powder. The four groups of scaffolds were termed PCL, 30% Pearl/PCL, 50% Pearl/PCL and 80% Pearl/PCL scaffolds according to the proportion of pearl powder. The samples were systematically investigated by scanning electron microscopy (SEM), wide-angle XRD, liquid substitution, Zwick static materials testing, and energy dispersive X-ray analysis. Biological characterization included SEM, fluorescent staining using calcein-AM, cell counting kit-8 assay, alkaline phosphatase and qRT-PCR analysis. The results show that the pore size and the pore morphology of the scaffolds are closely controlled via 3-D printing. This is very beneficial for tissue growth and nutrition transmission. The regular and uniform square macropore structure ensured that the pearl powder/PCL scaffolds had favorable mechanical strength. As the concentration of pearl powder in the scaffolds increase, the compressive strength and apatite formation increase as well as cell adhesion, proliferation, and osteogenic differentiation. These results show that pearl powder/PCL scaffolds fit the requirements of bone tissue engineering. The structures as well as physicochemical and biological properties of pearl powder/PCL composite scaffolds are positively associated with pearl powder concentrations.     

Macroporous elastomeric scaffolds with extensive micropores for soft tissue engineering

Macroporous scaffolds are of great value in tissue engineering. We have developed a method to fabricate macroporous scaffolds from a biocompatible and biodegradable elastomer, poly(glycerol sebacate) (PGS). This method is potentially very useful for soft tissue engineering. Our fabrication method produced macroporous scaffolds with extensive micropores. We fabricated flat scaffolds and tubular scaffolds of uniform thickness. This fabrication method demonstrated good control of variables such as pore size, porosity, and pore interconnectivity. Sodium chloride (salt) crystals, which served as solid porogens, were packed into a mold and fused in a humid chamber. PGS was cured while dispersed throughout the fused salt template. Dissolution of the salt and subsequent lyophilization produced elastomer sponges with approximately 90% porosity, interconnected macropores (75-150 microm), and extensive micropores (5-20 microm). The macropores were generated by the salt particles, while the micropores were likely generated by glycerol vapor formed during PGS curing. Such numerous micropores could facilitate cell-cell interactions and mass transport. Fibroblasts adhered to and proliferated well within the PGS scaffolds and formed three-dimensional tissue-engineered constructs within 8 days.     

Biomineralized porous composite scaffolds prepared by chemical synthesis for bone tissue regeneration

Scaffold design is a key factor in the clinical success of bone tissue engineering grafts. To date, no existing single biomaterial used in bone repair and regeneration fulfils all the requirements for an ideal bone graft. In this study hydroxyapatite/polycaprolactone (HA/PCL) composite scaffolds were prepared by a wet chemical method at room temperature. The physico-chemical properties of the composite materials were characterized by X-ray diffraction, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, while scaffold morphology was investigated by scanning electron microscopy (SEM) with energy-dispersive spectroscopy to validate the process used for synthesis. Finally, the response of bone marrow-derived human mesenchymal stem cells (hMSCs) in terms of cell proliferation and differentiation to the osteoblastic phenotype was evaluated using the Alamar blue assay, SEM and alkaline phosphatase activity. Microstructural analysis indicated that the HA particles were distributed homogeneously within the PCL matrix. The biological results revealed that the HA/PCL composite scaffolds are suitable for the proliferation and differentiation of MSCs in vitro, supporting osteogenesis after 15 days. All the results indicate that these scaffolds meet the requirements of materials for bone tissue engineering and could be used for many clinical applications in orthopaedic and maxillofacial surgery.     

Fabrication, mechanical and in vivo performance of polycaprolactone/tricalcium phosphate composite scaffolds

This paper explores the use of selective laser sintering (SLS) for the generation of bone tissue engineering scaffolds from polycaprolactone (PCL) and PCL/tricalcium phosphate (TCP). Different scaffold designs are generated, and assessed from the point of view of manufacturability, porosity and mechanical performance. Large scaffold specimens are produced, with a preferred design, and are assessed through an in vivo study of the critical size bone defect in sheep tibia with subsequent microscopic, histological and mechanical evaluation. Further explorations are performed to generate scaffolds with increasing TCP content. Scaffold fabrication from PCL and PCL/TCP mixtures with up to 50 mass% TCP is shown to be possible. With increasing macroporosity the stiffness of the scaffolds is seen to drop; however, the stiffness can be increased by minor geometrical changes, such as the addition of a cage around the scaffold. In the animal study the selected scaffold for implantation did not perform as well as the TCP control in terms of new bone formation and the resulting mechanical performance of the defect area. A possible cause for this is presented.     

Fiber templating of poly(2-hydroxyethyl methacrylate) for neural tissue engineering

We have developed a method to create longitudinally oriented channels within poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels for neural tissue engineering applications. Incorporated into an entubulation strategy, these scaffolds have the potential to enhance nerve regeneration after transection injuries of either the spinal cord or the peripheral nerve by increasing the available surface area and providing guidance to extending axons and invading cells. The fabrication process is straightforward and the resultant scaffolds are highly reproducible. Polycaprolactone (PCL) fibers were extruded and embedded in transparent, crosslinked pHEMA gels. Sonication of the pHEMA/PCL composite in acetone resulted in the complete dissolution of the PCL, leaving longitudinally oriented, fiber-free channels in the pHEMA gel. Regulating the size and quantity of the PCL fibers allowed us to control the diameter and number of channels. Small and large channel scaffolds were fabricated and thoroughly characterized. The small channel scaffolds had 142+/-7 channels, with approximately 75% of the channels in the 100-200 micro m size range. The large channel scaffolds had 37+/-1 channels, with approximately 77% of the channels in the 300-400 micro m range. The equilibrium water content (EWC), porosity and compressive modulus were measured for each of the structures. Small and large channel scaffolds had, respectively, EWCs of 55.0+/-1.2% and 56.2+/-2.9%, porosities of 35+/-1% and 40+/-1% and compressive moduli of 191+/-7 and 182+/-4kPa.     

Reinforcement of electrospun membranes using nanoscale Al2O3 whiskers for improved tissue scaffolds

Poly(ε-caprolactone) (PCL) is a promising material for tissue engineering applications; however, it can be difficult to create scaffolds with the morphology, hydrophilicity, and mechanical properties necessary to support tissue growth. Typically, pure PCL scaffolds have good cellular adhesion, but somewhat low mechanical properties (elastic modulus and tensile strength). This study addresses these issues by incorporating Al(2)O(3) whiskers as reinforcements within PCL membranes generated by electrospinning. Membranes were prepared with Al(2)O(3) content ranging from 1 to 20 wt % and characterized using XRD, TEM, and SEM to determine composition and morphology. The Al(2)O(3) whiskers were well dispersed within the PCL fibers, and the membranes had a highly porous morphology. The elastic modulus was significantly improved by the well aligned whisker reinforcements as verified by tensile testing. The cell morphology and proliferation studies demonstrate Al(2)O(3) whisker reinforced PCL scaffolds maintained the good biocompatibility. These improvements demonstrate that Al(2)O(3) whisker reinforced PCL scaffolds can be considered as a biocompatible material for tissue engineering and dental applications.     

Solid Free-Form Fabrication-Based PCL/HA Scaffolds Fabricated with a Multi-head Deposition System for Bone Tissue Engineering

In this study, we fabricated polycaprolactone/hydroxyapatite (PCL/HA) scaffolds with a multi-head deposition system, a solid free-form fabrication technology that was developed in our previous study. The bone regeneration potential of the scaffolds was compared with that of PCL scaffolds fabricated with the same system. The fabricated scaffolds had a pore size of 400 μm and a porosity of 66.7%. The PCL/HA scaffolds had higher mechanical strength and modulus than the PCL scaffolds. To compare the osteogenic potential, the two types of scaffolds were seeded with rat osteoblasts and cultured in vitro or implanted subcutaneously into athymic mice. The cells cultured on PCL/HA scaffolds expressed higher levels of osteopontin and osteonectin, both of which are osteogenic proteins. The PCL/HA scaffolds resulted in larger bone area and calcium deposition in the implants compared to the PCL scaffolds.     

Micromechanical finite-element modeling and experimental characterization of the compressive mechanical properties of polycaprolactone-hydroxyapatite composite scaffolds prepared by selective laser sintering for bone tissue engineering

Bioresorbable scaffolds with mechanical properties suitable for bone tissue engineering were fabricated from polycaprolactone (PCL) and hydroxyapatite (HA) by selective laser sintering (SLS) and modeled by finite-element analysis (FEA). Both solid gage parts and scaffolds having 1-D, 2-D and 3-D orthogonal, periodic porous architectures were made with 0, 10, 20 and 30 vol.% HA. PCL:HA scaffolds manufactured by SLS had nearly full density (99%) in the designed solid regions and had excellent geometric and dimensional control. Through optimization of the SLS process, the compressive moduli for our solid gage parts and scaffolds are the highest reported in the literature for additive manufacturing. The compressive moduli of solid gage parts were 299.3, 311.2, 415.5 and 498.3 MPa for PCL:HA loading at 100:0, 90:10, 80:20 and 70:30, respectively. The compressive effective stiffness tended to increase as the loading of HA was increased and the designed porosity was lowered. In the case of the most 3-D porous scaffold, the compressive modulus more than doubled from 14.9 to 36.2 MPa when changing the material from 100:0 to 70:30 PCL:HA. A micromechanical FEA model was developed to investigate the reinforcement effect of HA loading on the compressive modulus of the bulk material. Using a first-principles based approach, the random distribution of HA particles in a solidified PCL matrix was modeled for any HA loading to predict the bulk mechanical properties of the composites. The bulk mechanical properties were also used for FEA of the scaffold geometries. The results of the FEA were found to be in good agreement with experimental mechanical testing. The development of patient- and site-specific composite tissue-engineering constructs with tailored properties can be seen as a direct extension of this work on computational design, a priori modeling of mechanical properties and direct digital manufacturing.     

Fabrication and characterization of six electrospun poly(alpha-hydroxy ester)-based fibrous scaffolds for tissue engineering applications

The most common synthetic biodegradable polymers being investigated for tissue engineering applications are FDA approved, clinically used poly(alpha-hydroxy esters). To better assess the applicability of the electrospinning technology for scaffold fabrication, six commonly used poly(alpha-hydroxy esters) were used to prepare electrospun fibrous scaffolds, and their physical and biological properties were also characterized. Our results suggest that specific, optimized fabrication parameters are required for each polymer to produce scaffolds that consist of uniform structures morphologically similar to native extracellular matrix. Scanning electron microscopy (SEM) revealed a highly porous, three-dimensional structure for all scaffolds, with average fiber diameter ranging from 300nm to 1.5microm, depending on the polymer type used. The poly(glycolic acid) (PGA) and poly(d,l-lactic-co-glycolic acid 50:50) (PLGA5050) fibrous structures were mechanically stiffest, whereas the poly(l-lactic acid) (PLLA) and poly(epsilon-caprolactone) (PCL) scaffolds were most compliant. Upon incubation in physiological solution, severe structural destruction due to polymer degradation was found in the PGA, poly(d,l-lactic acid) (PDLLA), PLGA5050, and poly(d,l-lactic-co-glycolic acid 85:15) (PLGA8515) fibrous scaffolds, whereas PLLA and PCL fibrous scaffolds maintained a robust scaffold structure during the same time period, based on macroscopic and SEM observations. In addition, PLLA scaffolds supported the highest rate of proliferation of seeded cells (chondrocytes and mesenchymal stem cells) than other polymeric scaffolds. Our findings showed that PLLA and PCL based fibrous scaffolds exhibited the most optimal structural integrity and supported desirable cellular response in culture, suggesting that such scaffolds may be promising candidate biomaterials for tissue engineering applications.     

A mesoporous bioactive glass/polycaprolactone composite scaffold and its bioactivity behavior

Composite scaffolds of mesoporous bioactive glass (MBG)/polycaprolactone (PCL) and conventional bioactive glass (BG)/PCL were fabricated by a solvent casting-particulate leaching method, and the structure and properties of the composite scaffolds were characterized. The measurements of the water contact angles suggest that the incorporation of either MBG or BG into PCL can improve the hydrophilicity of the composites, and the former is more effective than the later. The bioactivity of the composite scaffold is evaluated by soaking the scaffolds in a simulated body fluid (SBF) and the results show that the MBG/PCL composite scaffolds can induce a dense and continuous layer of apatite after soaking in SBF for 3 weeks, as compared with the scattered and discrete apatite particles on the BG/PCL composite scaffolds. Such improvements (improvements of the hydrophilicity and apatite forming ability) should be helpful for the extensive applications of PCL scaffold in tissue engineering.     

Effect of conditioning methods on the microtensile bond strength of phosphate monomer-based cement on zirconia ceramic in dry and aged conditions

Scaffold fabrication for regenerating functional human tissues has an important role in tissue engineering, and there has been much progress in research on scaffold fabrication. However, current methods are limited by the mechanical properties of existing biodegradable materials and the irregular structures that they produce. Recently, several promising biodegradable materials have been introduced, including poly(propylene fumarate) (PPF). The development of micro-stereolithography allows the fabrication of free-form 3D microstructures as designed. Since this technology requires a low-viscosity resin to fabricate fine structures, we reduced the viscosity of PPF by adding diethyl fumarate. Using our system, the curing characteristics and material properties of the resin were analyzed experimentally. Then, we fabricated waffle shape and 3D scaffolds containing several hundred regular micro pores. This method controlled the pore size, porosity, interconnectivity, and pore distribution. The results show that micro-stereolithography has big advantages over conventional fabrication methods. In addition, the ultimate strength and elastic modulus of the fabricated scaffolds were measured, and cell adhesion to the fabricated scaffold was observed by growing seeded cells on it. These results showed that the PPF/DEF scaffold is a potential bone scaffold for tissue engineering.     

Three dimensional melt-deposition of polycaprolactone/bio-derived hydroxyapatite composite into scaffold for bone repair

In this study, three dimensional (3D) polycaprolactone/bio-derived hydroxyapatite (PCL/BHA) composite scaffolds were fabricated by using a melt-deposition system (MDS) for the applications in bone repair. PCL/BHA composites with BHA contents of 0, 10, 20, and 40% were successfully processed into 3D scaffolds by using MDS, while it was failed to fabricate PCL/BHA scaffold with BHA content of 60%. The scaffolds produced were demonstrated to possess the same structures as the predefined with highly uniform and completely interconnected pores. The compressive modulus and strength of the PCL/BHA scaffold increased from 27 to 56?MPa and from 1.9 to 4.5?MPa, respectively, as BHA content increased from 0 to 40%. The wettability of PCL/BHA composite scaffold was also improved with the increase of BHA content. Moreover, the PCL/BHA scaffolds fabricated by MDS showed satisfactory biocompatibility and were capable of being integrated with the surrounding host bone. This study shows the feasibility of fabricating 3D PCL/BHA composite scaffolds with favorable pore structures, mechanical properties, wettability and biocompatibility by using MDS and supports further research of developing novel PCL/BHA composite scaffolds with MDS for the applications in bone repair.     

Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering

Polycaprolactone (PCL) is a bioresorbable polymer with potential applications for bone and cartilage repair. In this work, porous PCL scaffolds were computationally designed and then fabricated via selective laser sintering (SLS), a rapid prototyping technique. The microstructure and mechanical properties of the fabricated scaffolds were assessed and compared to the designed porous architectures and computationally predicted properties. Scaffolds were then seeded with bone morphogenetic protein-7 (BMP-7) transduced fibroblasts and implanted subcutaneously to evaluate biological properties and to demonstrate tissue in-growth. The work done illustrates the ability to design and fabricate PCL scaffolds with porous architecture that have sufficient mechanical properties for bone tissue engineering applications using SLS. Compressive modulus and yield strength values ranged from 52 to 67 MPa and 2.0 to 3.2 Mpa, respectively, lying within the lower range of properties reported for human trabecular bone. Finite element analysis (FEA) results showed that mechanical properties of scaffold designs and of fabricated scaffolds can be computationally predicted. Histological evaluation and micro-computed tomography (microCT) analysis of implanted scaffolds showed that bone can be generated in vivo. Finally, to demonstrate the clinical application of this technology, we designed and fabricated a prototype mandibular condyle scaffold based on an actual pig condyle. The integration of scaffold computational design and free-form fabrication techniques presented here could prove highly useful for the construction of scaffolds that have anatomy specific exterior architecture derived from patient CT or MRI data and an interior porous architecture derived from computational design optimization.