Calcium Phosphate Composite Scaffolds Research Articles

Enhanced Bone Healing in Critical-Sized Rabbit Femoral Defects: Impact of Helical and Alternate Scaffold Architectures.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. We explored two distinct scaffold designs to assess their influence on bone healing and scaffold performance. Structures with alternate (0°/90°) and helical (0°/45°/90°/135°/180°) laydown patterns were manufactured with a 3D printer using a fused deposition modeling technique. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a femoral condyle critical defect model in eight skeletally mature New Zealand White rabbits. Then, the results were analyzed micro-tomographically, histologically, and histomorphometrically. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites.

Toughening robocast chitosan/biphasic calcium phosphate composite scaffolds with silk fibroin: Tuning printable inks and scaffold structure for bone regeneration

The present work aims the production of composite bioceramic scaffolds by robocasting suppressing sintering as post printing process. To achieve this purpose, extrudable ink compositions containing a high concentration of bioceramic powders (hydroxyapatite and β-tricalcium phosphate) embedded in aqueous polymeric solutions of chitosan and silk fibroin were fine-tuned. Polymeric solutions of chitosan/silk fibroin with different ratios were tested, maintaining the total amount of bioceramic solids at 30 vol%. The inks were characterized by rheological studies in viscometry and oscillatory modes, being the printable ones selected to produce scaffolds with different macropore sizes (300 μm and 500 μm). The scaffolds were characterized by mechanical properties (dry and wet conditions) and morphological features, as well as its degradability. In vitro studies were also evaluated in the scaffolds that presented the best structural performance.The addition of 2 wt% silk fibroin to a 5 wt% chitosan matrix allows to significantly improve the mechanical performance of the printed composite scaffolds, reflected in high values for Young's modulus and maximum compressive strength. This trend was continued in wet scaffolds with a concomitant reduction of mechanical properties. Regarding degradability, the scaffolds in general presented a weight loss in the range of 14–18% after 28 days incubation in HEPES solution at two different pH values at 37 °C, with an associated release of calcium and phosphorus ions. The scaffold with 300 μm porosity comprising the both polymers in its composition presented the less rate degradation when compared to the scaffolds with similar porosity and containing only chitosan as base matrix. Moreover, the combined natural polymers gave rise to a significant increase in the metabolic activity of human osteoblasts grown on the scaffolds with both macropore' size, being in line with the full cellular filling of their surfaces, demonstrated by SEM and confocal imaging. The advances presented in this work are a promising path in the ink's development for extrusion-based additive manufacturing techniques and subsequent biomaterials, encompassing suitable physical and chemical characteristics with high potential to be used as bone substitutes.

Multifunctional silicon calcium phosphate composite scaffolds promote stem cell recruitment and bone regeneration.

A scaffold is one of the most significant implants for treating bone injury, while the precise control of stem cell proliferation and differentiation within a scaffold is still challenging. In this work, a composite scaffold was designed to be capable of recruiting endogenous stem cells, stimulating osteogenic differentiation and achieving significant bone repair function. The designed SiCP + SF@PFS silica-calcium phosphate composite scaffold was obtained by mixing the peptide PFS containing silk fibroin solution with the SiCP scaffold, and treating with horseradish peroxidase and H2O2. The results showed that the composite scaffold was able to release the PFS peptide continuously to induce the migration of mesenchymal stem cells. Meanwhile, cell proliferation and osteogenic differentiation were also improved after being seeded on the scaffold. In the cranial defect rat model, the composite scaffold was able to recruit CD29+ and CD90+ cells one week after implantation around the injury sites. The results of Micro-CT, H&E staining, Masson's staining and immunohistochemical staining indicated that the composite scaffold was able to promote new bone formation significantly.

Development of carboxymethylcellulose based composites for bone tissue engineering

The present study focuses on the development of carboxymethylcellulose (CMC)–biphasic calcium phosphate (BCP) composite scaffolds through the freeze-drying process for bone tissue engineering applications. Citric acid or fumaric acid was added as the cross-linker of CMC to improve the stability of composite scaffolds. The effect of change in freezing temperature (−20, −40 or −80°C) on the pore morphology, swelling ability and mechanical properties of composite scaffolds was studied. Cross-linked scaffolds showed an increased thermal degradation temperature compared with non-cross-linked scaffolds. All the composite scaffolds showed a porous structure with homogeneous blending of CMC and BCP. Cross-linked scaffolds showed appreciable swelling ability and stability in phosphate-buffered saline, while non-cross-linked scaffolds were unstable for 24 h. Cross-linked scaffolds had lower compressive strength than non-cross-linked scaffolds under dry conditions. However, in the hydrated state, only citric acid-cross-linked scaffolds were stable with improved compressive strength of 64 ± 4, 57 ± 4 and 67 ± 4 kPa when processed at −20, −40 and −80°C, respectively. Furthermore, three-dimensional culture of Saos-2 cells on citric acid-cross-linked scaffolds showed their suitability for cell proliferation and osteogenic differentiation. Therefore, citric acid-cross-linked CMC–BCP composite scaffolds may be promising scaffolds for bone tissue engineering applications.

3D Plotting using Camphene as Pore-regulating Agent to Produce Hierarchical Macro/micro-porous Poly(ε-caprolactone)/calcium phosphate Composite Scaffolds.

This study demonstrates the utility of camphene as the pore-regulating agent for phase separation-based 3D plotting to produce hierarchical macro/micro-porous poly(ε-caprolactone) (PCL)–calcium phosphate (CaP) composite scaffolds, specifically featuring highly microporous surfaces. Unlike conventional particulate porogens, camphene is highly soluble in acetone, the solvent for PCL polymer, but insoluble in coagulation medium (water). In this study, this unique characteristic supported the creation of numerous micropores both within and at the surfaces of PCL and PCL–CaP composite filaments when using high camphene contents (40 and 50 wt%). In addition, the incorporation of the CaP particles into PCL solutions did not deteriorate the formation of microporous structures, and thus hierarchical macro/micro-porous PCL–CaP composite scaffolds could be successfully produced. As the CaP content increased, the in vitro biocompatibility, apatite-forming ability, and mechanical properties (tensile strength, tensile modulus, and compressive modulus) of the PCL–CaP composite scaffolds were substantially improved.

Hierarchically porous structure, mechanical strength and cell biological behaviors of calcium phosphate composite scaffolds prepared by combination of extrusion and porogen burnout technique and enhanced by gelatin

In this study, hierarchically porous calcium phosphate scaffolds (HTCP) with unidirectional pores, transversely interconnected pores, and micropores were fabricated by the combination of extrusion and porogen burnout technique. Gelatin was incorporated into the HTCP scaffolds by vacuum-impregnation of gelatin solution and subsequent freeze-drying. The phase composition, microstructure, physical and cytobiological properties were analyzed. The results showed that the HTCP scaffolds were composed of β-tricalcium phosphate with minor hydroxyapatite. The HTCP scaffolds had unidirectional pores (~400μm), transversely interconnected pores (~130μm) and micropores (~1μm). The incorporation of gelatin significantly increased the compressive strength, toughness, and cell seeding of the HTCP scaffolds. The composite scaffolds showed excellent cytocompatibility. The hierarchically porous calcium phosphate composite scaffolds may have potential application prospects in bone tissue engineering.

In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head

Avascular necrosis of the femoral head (ANFH) is difficult to treat due to high pressure and hypoxia, and reduced levels of growth factors such as bone morphogenetic protein (BMP), and vascular endothelial growth factor (VEGF). We generated a novel calcium phosphate (CPC) composite scaffold, which contains BMP-VEGF-loaded poly-lactic-co-glycolic acid (PLGA) microspheres (BMP-VEGF-PLGA-CPC). The BMP-VEGF-loaded microspheres have an encapsulation efficiency of 89.15% for BMP, and 78.55% for VEGF. The BMP-VEGF-PLGA-CPC scaffold also demonstrated a porosity of 62% with interconnected porous structures, and pore sizes of 219μm and compressive strength of 6.60MPa. Additionally, bone marrow mesenchymal stem cells (BMSCs) were seeded on scaffolds in vitro. Further characterization showed that the BMP-VEGF-PLGA-CPC scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. Using a rabbit model of ANFH, BMP-VEGF-PLGA-CPC scaffolds were implanted into the bone tunnels of core decompression in the femoral head for 6 and 12weeks. Radiographic and histological analysis demonstrated that the BMP-VEGF-PLGA-CPC scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. These results indicate that the BMP-VEGF-PLGA-CPC scaffold may improve the therapeutic effect of core decompression surgery and be used as a treatment for ANFH.

Biocompatibility and osteogenesis of calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres for bone tissue engineering.

By utilizing a modified solid/oil/water (s/o/w) emulsion solvent evaporation technique, calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres (SIM-PLGA-CPC) were prepared in this study. We characterized the morphology, encapsulation efficiency and in vitro drug release of SIM-loaded PLGA microspheres as well as the macrostructure, pore size, porosity and mechanical strength of the scaffolds. Rabbit bone mesenchymal stem cells (BMSCs) were seeded onto SIM-PLGA-CPC scaffolds, and the proliferation, morphology, cell cycle and differentiation of BMSCs were investigated using the cell counting kit-8 (CCK-8) assay, scanning electron microscopy (SEM), flow cytometry, alkaline phosphatase (ALP) activity and alizarin red S staining, respectively. The results revealed that SIM-PLGA-CPC scaffolds were biocompatible and osteogenic in vitro. To determine the in vivo biocompatibility and osteogenesis of the scaffolds, both pure PLGA-CPC scaffolds and SIM-PLGA-CPC scaffolds were implanted in rabbit femoral condyles and microradiographically and histologically investigated. SIM-PLGA-CPC scaffolds exhibited good biocompatibility and could improve the efficiency of new bone formation. All these results suggested that the SIM-PLGA-CPC scaffolds fulfilled the basic requirements of bone tissue engineering scaffold and possessed application potentials in orthopedic surgery.

The effect of calcium phosphate composite scaffolds on the osteogenic differentiation of rabbit dental pulp stem cells.

The objective of this study is to compare the effects of the two calcium phosphate composite scaffolds on the attachment, proliferation, and osteogenic differentiation of rabbit dental pulp stem cells (DPSCs). One nano-hydroxyapatite/collagen/poly (l-lactide) (nHAC/PLA), imitating the composition and the micro-structure characteristics of the natural bone, was made by Beijing Allgens Medical Science & Technology Co., Ltd. (China). The other beta-tricalcium phosphate (β-TCP), being fully interoperability globular pore structure, was provided by Shanghai Bio-lu Biomaterials Co, Ltd. (China). We compared the absorption water rate and the protein adsorption rate of two scaffolds and the characterization of DPSCs cultured on the culture plate and both scaffolds under osteogenic differentiation media (ODM) treatment. The constructs were then implanted subcutaneously into the back of severely combined immunodeficient (SCID) mice for 8 and 12 weeks to compare their bone formation capacity. The results showed that the ODM-treated DPSCs expressed osteocalcin (OCN), bone sialoprotein (BSP), type I collagen (COLI) and osteopontin (OPN) by immunofluorescence staining. Positive alkaline phosphatase (ALP) staining, calcium deposition and calcium nodules were also observed on the ODM-treated DPSCs. The absorption water rate and protein adsorption rate of nHAC/PLA was significantly higher than β-TCP. The initial attachment of DPSCs seeded onto nHAC/PLA was significantly higher than that onto β-TCP; and the proliferation rate of the cells was also significantly higher than that of β-TCP on 1, 3, and 7 days of cell culture. The ALP activity, calcium/phosphorus content and mineral formation of DPSCs + β-TCP were significantly higher than DPSCs + nHAC/LA. When implanted into the back of SCID mice, nHAC/PLA alone had no new bone formation, newly formed mature bone and osteoid were only observed in β-TCP alone, DPSCs + nHAC/PLA and DPSCs + β-TCP, and this three groups displayed increased bone formation over the 12-week period. The percentage of total bone formation area had no difference between DPSCs + β-TCP and DPSCs + nHAC/PLA at each time point, but the percentage of mature bone formation area of DPSCs + β-TCP was significantly higher than that of DPSCs + nHAC/PLA. Our results demonstrated that the DPSCs on nHAC/PLA had a better proliferation, and that the DPSCs on β-TCP had a more mineralization in vitro, much more newly formed mature bones in vivo were presented in DPSCs + β-TCP group. These findings have provided a further knowledge that scaffold architecture has different influence on the attachment, proliferation and differentiation of cells. This study may provide insight into the clinical periodontal bone tissue repair with DPSCs + β-TCP construct.

Promotion of human mesenchymal stem cell differentiation on bioresorbable polycaprolactone/biphasic calcium phosphate composite scaffolds for bone tissue engineering

An artificial construct mimicking the intrinsic properties of the natural extracellular matrix in bones has been considered an ideal platform for bone tissue engineering, as it can present an appropriate microenvironment and regulate cell behaviours. In this report, we introduce biodegradable composite scaffolds consisting of polycaprolactone (PCL) and biphasic calcium phosphate (BCP). The scaffolds were fabricated by a salt-leaching process, and the ability of the scaffolds to facilitate osteogenic differentiation was investigated using human mesenchymal stem cells (hMSCs). The scaffolds had an inter-connected porous structure with quadrilateral pores of approximately 200 ∼ 500 μm in width. The mechanical properties of the scaffolds changed as the BCP content was increased in the starting mixture. In the hMSC experiment, although we found that hMSCs adhered to the surface, as well as the inside, of the scaffolds, the incorporated BCP did not increase the proliferation of the hMSCs over 7 days in culture. Interestingly, the alkaline phosphatase (ALP) activity was 4 times higher on the PCL/BCP composite scaffold (0.12 ± 0.03 nmol/min/μg protein) thanon the PCL scaffold (0.03 ± 0.01 nmol/min/μg protein), suggesting that BCP can aid in generating a local environment that promotes bone regeneration. Therefore, a strategy combining polymers and ceramics can be considered a useful platform for bone tissue engineering.

Preparation and Properties of Supermagnetic Calcium Phosphate Composite Scaffold

Preparation and Properties of Supermagnetic Calcium Phosphate Composite Scaffold

The effect of composition of calcium phosphate composite scaffolds on the formation of tooth tissue from human dental pulp stem cells

Different approaches towards making 3-dimensional (3-D) bioengineered tooth for future replacement therapy have been developed including scaffold-based tooth regeneration. However, selection of optimal scaffold for future clinical application remains a challenge. In the present study, we tested biocompatibility of four different types of 3-D scaffolds for tooth-tissue regeneration, including a pure poly(lactide-co-glycolide) (PLGA) (70/30, mol/mol) scaffold and three types of calcium phosphate contained composites scaffolds that were 50 wt% of PLGA combined with 50 wt% of hydroxyapatite (HA), tricalcium phosphate (TCP) or calcium carbonate hydroxyapatite (CDHA) respectively. These scaffolds were fabricated by the particle leaching in combination with phase separation technology. Surface modification of these scaffolds was further performed by an ammonia plasma treatment and anchorage of collagen technology. Effect of composition of the composite scaffolds on proliferation of human dental pulp stem cells (DPSCs) was accessed using in vitro MTT assay and in vivo BrdU labeling. Differentiation capability of the DPSCs in the scaffolds was analyzed by measurement of the levels of calcified tissue formation and ALP activity. Our results showed that while the calcium phosphate contained compound is able to support regeneration of tooth tissue effectively, the PLGA/TCP scaffold is more appropriate for the proliferation and differentiation of DPSCs. Furthermore, seeding of dissociated 4-dpn rat tooth bud cells on the PLGA/TCP scaffold generated dentin- and pulp-like tissues. Our results demonstrate that the PLGA/TCP scaffold is superior to the other three scaffolds for tooth-tissue regeneration, especially for dentin formation.

Preparation and mechanical behavior of PLGA/nano-BCP composite scaffolds during in-vitro degradation for bone tissue engineering

In this paper, the yield strength and elastic modulus of Poly (lactide-co-glycolide) (PLGA) and PLGA/nano-biphasic calcium phosphate (nBCP) composite scaffolds, before and during in-vitro degradation, have been evaluated. Composite scaffolds were made by using PLGA matrix and 10–50 wt.% nBCP powder as the reinforcement material. All scaffolds, with more than 89% porosity, were fabricated by thermally-induced phase separation (TIPS). During in-vitro degradation (0–8 weeks), the PLGA/nBCP scaffolds showed both more weight loss and better mechanical properties as compared to neat PLGA scaffolds. The PLGA/nBCP scaffolds with 30 wt.% nBCP illustrated the highest value of yield strength among the composite scaffolds, before and after degradation, until 6 weeks. After 8 weeks, the yield strength values were very poor and close to each other. The values of elastic modulus for all samples were less than the half of their initial values after 6 weeks. However, after 8 weeks, the elastic moduli of all samples reduced to negligible values.

Biomimetic bone scaffolds based on chitosan and calcium phosphates

This paper reports a novel biomimetic technique for obtaining chitosan–calcium phosphate composite scaffolds (Cs–CP) by calcium phosphate precipitation from its precursors,CaCl 2 and NaH 2PO 4 in the presence of ammonia and Cs, followed by product freeze-drying. The structural and morphological analysis showed the arrangement of CP onto Cs fibers, while Cs acting as glue to bind together the CP crystals. The presence of different forms of CP was evidenced, including hydroxyapatite, which is known to be involved in the formation of the new bone tissue in living organisms. Great mechanical properties of the scaffolds indicate their potential use in bone tissue engineering.

Development and characterization of nanofibrous poly(lactic-co-glycolic acid)/biphasic calcium phosphate composite scaffolds for enhanced osteogenic differentiation

Poly(lactic-co-glycolic acid)(PLGA)/biphasic calcium phosphate (BCP) composite nanofibers with different BCP to PLGA ratios were fabricated using the electrospinning technique. The scanning electron microscopy (SEM) images showed a similar morphology and fibers in all groups. The incorporated BCP was dispersed homogenously throughout the nanofibers, and the surface roughness was affected by the input amount of BCP. The increase in amount of BCP incorporated was confirmed by several methods. BCP incorporation into the PLGA nanofibers did not affect the initial adhesion of osteoblasts and their adherent morphology. However, the proliferation of the cells cultured on the composite nanofibers for 10 days with larger amounts of BCP was delayed, suggesting that incorporated BCP may facilitate the switch from proliferation to differentiation of the osteoblasts. The incorporation of BCP enhanced the expression of osteogenic genes, as well as induced calcium deposition by the osteoblasts in the extracellular matrix(ECM) after 21 days of culture on the PLGA/BCP composite nanofibers. Overall, these results can provide evidence of the potential of BCP incorporation into the biomaterials for effective bone regeneration.

Self-Hardening Calcium Phosphate Composite Scaffold for Bone Tissue Engineering

Calcium phosphate cement (CPC) sets in situ to form solid hydroxyapatite, can conform to complex cavity shapes without machining, has excellent osteoinductivity, and is able to be resorbed and replaced by new bone. Therefore, CPC is promising for craniofacial and orthopaedic repairs. However, its low strength and lack of macroporosity limit its use. This study investigated CPC reinforcement with absorbable fibers, the effects of fiber volume fraction on mechanical properties and macroporosity, and the biocompatibility of CPC-fiber composite. The liquid phase of CPC in this study was the weak acidic solution of chitosan. Chitosan has favourable biocompatibility, which has high viscosity in solution. The incorporation of chitosan could improve the handling properties of CPC. The liquid phase contained citric acid could strongly improve the hydration rate of CPC, which shortened the setting time and increased the compressive strength of CPC. In addition, the weak acidic environment around the biomaterials could accelerate the degradation of CPC, which was important to bone tissue engineering. The rationale was that large-diameter absorbable fibers would initially strengthen the CPC graft, then dissolve to form long cylindrical macropores for colonization by osteoblasts. Compressive strength was measured vs. fiber volume fraction from 0% (CPC Control without fibers) to 70%. Animal experiment showed that the material had osteoinductivity and biodegradability when the material was implanted into the muscle pouches in the thigh of rabbits. Compressive strength (mean ± SD; n=3) of CPC with 70% fibers was 0.8± 0.1 MPa. Long cylindrical macropores 100~300 μm in diameter were created in CPC after fiber dissolution, and the CPC-fiber scaffold reached a total porosity of 75.1±1.2% with 70% fibers. The new CPC-fiber formulation had good potentiality of ectopic bone induction. The method of using large-diameter absorbable fibers in bone graft for mechanical properties and formation of long cylindrical macropores for bone ingrowth may be applicable to other tissue engineering materials.

Design and characterization of a novel chitosan/nanocrystalline calcium phosphate composite scaffold for bone regeneration

To meet the challenge of regenerating bone lost to disease or trauma, biodegradable scaffolds are being investigated as a way to regenerate bone without the need for an auto- or allograft. Here, we have developed a novel microsphere-based chitosan/nanocrystalline calcium phosphate (CaP) composite scaffold and investigated its potential compared to plain chitosan scaffolds to be used as a bone graft substitute. Composite and chitosan scaffolds were prepared by fusing microspheres of 500-900 microm in diameter, and porosity, degradation, compressive strength, and cell growth were examined. Both scaffolds had porosities of 33-35% and pore sizes between 100 and 800 . However, composite scaffolds were much rougher and, as a result, had 20 times more surface area/unit mass than chitosan scaffolds. The compressive modulus of hydrated composite scaffolds was significantly higher than chitosan scaffolds (9.29 +/- 0.8 MPa vs. 3.26 +/- 2.5 MPa), and composite scaffolds were tougher and more flexible than what has been reported for other chitosan-CaP composites or CaP scaffolds alone. Using X-ray diffraction, scaffolds were shown to contain partially crystalline hydroxyapatite with a crystallinity of 16.7% +/- 6.8% and crystallite size of 128 +/- 55 nm. Fibronection adsorption was increased on composite scaffolds, and cell attachment was higher on composite scaffolds after 30 min, although attachment rates were similar after 1 h. Osteoblast proliferation (based on dsDNA measurements) was significantly increased after 1 week of culture. These studies have demonstrated that composite scaffolds have mechanical properties and porosity sufficient to support ingrowth of new bone tissue, and cell attachment and proliferation data indicate composite scaffolds are promising for bone regeneration.

Fabrication of a calcium phosphate scaffold with a three dimensional channel network and its application to perfusion culture of stem cells

PurposeThe purpose of this paper is to adopt rapid prototyping (RP) technology to fabricate self‐hardening calcium phosphate composite (CPC) scaffolds with a controlled internal channel network to facilitate nutrient supplying and cell growth using RP technique and investigate their in vitro performance.Design/methodology/approachPorous scaffolds should possess branched channels to ensure uniform cell feeding and even flow of culture medium to promote uniform cell attachment and growth. A new three dimensional (3D) flow channel structure has been designed based on conversation of energy and flow. The CPC scaffold possessing such a channel network was made by indirect solid free form fabrication. Negative model of scaffold was designed by Pro/E software and its epoxy resin mold was fabricated on a sterolithography apparatus and the CPC slurry was filled in these molds. After CPC was self hardened, the mold was baked. The mold was removed by pyrolysis and then the designed scaffold was obtained.FindingsThe sizes of the fabricated scaffolds were consistent with the designed. The average compressive strength of the scaffold is approximately 6.0 MPa. Computational fluid dynamics and perfusion culture results showed that such a 3D flow channel arrangement would lead to a more uniform distribution of flow and cells and good transportation of nutrients.Research limitations/implicationsThe size errors of fabricated scaffolds could not escape and perfusion methods were difficult to control.Originality/valueThe basic design concept presented showed great promise for use in bone tissue engineering and fabrication method enhanced the versatility of scaffold fabrication. The designed scaffold structure made it possible to keep integrality of the scaffold when direct observation cells inside the channel by scanning electron microscopy (SEM).

In situ synthesized ceramic–polymer composites for bone tissue engineering: bioactivity and degradation studies

As an alternative to current bone grafting strategies, a poly-lactide-co-glycolide/calcium phosphate composite microsphere-based scaffold has been synthesized by the direct formation of calcium phosphate within forming microspheres. It was hypothesized that the synthesis of low crystalline calcium phosphate within forming microspheres would provide a site-specific delivery of calcium ions to enhance calcium phosphate reprecipitation onto the scaffold. Both polymeric and composite scaffolds were incubated in simulated body fluid (SBF) for 8 weeks, during which time polymer molecular weight, scaffold mass, calcium ion concentration of SBF, pH of SBF, and calcium phosphate reprecipitation was monitored. Results showed a 20% decrease in polymeric scaffold molecular weight compared to 11–14% decrease for composite scaffolds over 8 weeks. Composite scaffold mass and SBF pH decreased for the first 2 weeks but began increasing after 2 weeks and continued to do so up to 8 weeks, suggesting interplay between pH changes and calcium phosphate dissolution/reprecipitation. Free calcium ion concentration of SBF containing composite scaffolds increased 20–40% over control values within 4 h of incubation but then dropped as low as 40% below control values, suggesting an initial burst release of calcium ions followed by a reprecipitation onto the scaffold surface. Scanning electron micrographs confirm calcium phosphate reprecipitation on the scaffold surface after only 3 days of incubation. Results suggest the composite scaffold is capable of initiating calcium phosphate reprecipitation which may aid in bone/implant integration.

Design and fabrication of CAP scaffolds by indirect solid free form fabrication

PurposeTo fabricate the self‐hardening calcium phosphate composite scaffolds with controlled internal pore architectures using rapid prototyping (RP) techniques and investigate their in vitro bone tissue engineering responses.Design/methodology/approachThe three‐dimensionally interconnected pores in scaffolds can facilitate sufficient supply of blood, oxygen and nutrients for the ingrowth of bone cells, tissue regeneration, and vascularization. It is essential for bone tissue engineering to provide an accurate control over the scaffolds material, porosity, and internal pore architectures. Negative image of scaffold was designed and epoxy resin molds were fabricated on sterolithography apparatus. Calcium phosphate cement slurry was cast in these molds. After self‐hardening, the molds were removed by pyrolysis and the resulting scaffolds were obtained.FindingsEight scaffolds with 54.45 percent porosity were tested on an Instron machine. The average compressive strength measured was 5.8±0.8 Mpa. Cytotoxicity and cell proliferation studies were conducted with rabbit osteoblast. Results showed that these scaffolds were non‐toxic and displayed excellent cell growth during the 2 weeks of in vitro culture.Research limitations/implicationsThe resulting scaffolds inherited errors and defects from the molds, such as cracks and dimensional changes.Originality/valueThe present method enhances the versatility of scaffold fabrication by RP. It is capable of reproducibly fabricating scaffolds from a variety of biomaterials.