Hydroxyapatite Tricalcium Phosphate Research Articles

On Modeling Bio-Scaffolds: Structural and Fluid Transport Characterization Based on 3-D Imaging Data

Bio-scaffolds which are most commonly open celled porous structures are increasingly used for tissue engineering and regenerative medicine. A number of studies have shown that the bulk properties of such irregular structures are poorly modeled using idealized unit cell approaches. The paper therefore uses novel image based meshing techniques to explore both fluid flow and bulk structural properties of a bone scaffold, as accurate modeling of bio-scaffolds with non-uniform cellular structures is very important for the development of optimal scaffolds for tissue engineering application. In this study, a porous hydroxyapatite/tricalcium phosphate (HA/TCP) bone scaffold has been scanned in a Micro-CT scanner, and converted into a volumetric mesh using image processing software developed by the authors. The resulting mesh was then exported to commercial FEA and CFD solvers for analysis. Initial FEA and CFD studies have shown promising results and have highlighted the importance of accurate modeling to understand how microstructures influence the mechanical property of the scaffold, and to analyze flow regimes through the sample. The work highlights the potential use of image based meshing for the ad hoc characterization of scaffolds as well as for assisting in the design of scaffolds with tailored strength, stiffness, and transport properties.

Bone regenerative properties of rat, goat and human platelet-rich plasma

To explore the reported contradictory osteogenic capacity of platelet-rich plasma (PRP), the aim of the study was to examine and compare the bone regenerative effect of: PRPs of different species (rat, goat, human); human bone graft (HB) vs. HB combined with human PRP (HB+hPRP); and HB+hPRP vs. synthetic hydroxyapatite-tricalcium phosphate bone substitute combined with hPRP (HA/TCP+hPRP). For this purpose, 72 implants, divided into 6 groups (n=6) were inserted in critical-sized defects of immunodeficient rats. After 2 and 4 weeks, descriptive and quantitative histological, and micro-CT analyses were performed on the specimens. Rat and goat PRP combined with HA/TCP did not enhance bone regeneration compared with HA/TCP. In contrast, human PRP combined with HA/TCP resulted in significantly increased bone fill compared to HA/TCP. The addition of human PRP to human bone graft increased significantly the amount of newly formed bone after 2 weeks. HB+hPRP demonstrated enhanced bone healing compared to HA/TCP+hPRP. In conclusion, rat and goat PRP had no effect on bone formation. Human PRP improved the initial osteogenic response of human bone graft. Human PRP combined with human bone graft had better osteogenic capacity than human PRP combined with synthetic bone substitute.

Mesenchymal stem cell–mediated ectopic hematopoiesis alleviates aging-related phenotype in immunocompromised mice

AbstractSubcutaneous transplants of bone marrow mesenchymal stem cells (BMMSCs) are capable of generating ectopic bone and organizing functional hematopoietic marrow elements in animal models. Here we report that immunocompromised mice received subcutaneous BMMSC transplants using hydroxyapatite tricalcium phosphate as a carrier suppressed age-related degeneration in multiple organs and benefited an increase in life span extension compared with control littermates. The newly organized ectopic bone/marrow system restores active hematopoiesis via the erythropoietin receptor/signal transducer and activator of transcription 5 (Stat5) pathway. Furthermore, the BMMSC recipient mice showed elevated level of Klotho and suppression of insulin-like growth factor I signaling, which may be the mechanism contributing to the alleviation of aging-like phenotypes and prolongation of life in the treated mice. This work reveals that erythropoietin receptor/Stat5 pathway contributes to BMMSC-organized ectopic hematopoiesis, which may offer a treatment paradigm of reversing age-related degeneration of multiple organs in adult immunocompromised mice.

The induction of dentin bridge-like structures by constructs of subcultured dental pulp-derived cells and porous HA/TCP in porcine teeth.

The purpose of this study was to investigate dentin-bridge formation in teeth following the transplantation of dental pulp-derived cells seeded on hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds. The dental pulp tissues were removed from the extracted first molar teeth of miniature pigs and single cell populations were subcultured. Second-passage cells that had alkaline phosphatase activity were combined with scaffolds. Cell-scaffold constructs were placed in contact with the exposed pulp tissue. The dimensions of the exposed pulp site were approximately 1-2.5 mm in diameter and 2-3 mm in depth from the tooth surface. After placing the constructs, the tooth was restored with composite resin. Six weeks after transplantation, hard tissue formation was observed on the pulp tissue in histology. Dentinal tubule-like structures were observed in most of the hard tissue generated, and columnar cells, which showed positive immunoreactions with dentin sialoprotein (DSP) and heat shock protein (HSP)-25, were aligned beneath the hard tissues. When only scaffolds were placed on the pulp tissues, particles of hard tissue were formed, however dentinal tubule-like structures and odontoblasts were not observed despite the formation of hard tissue. In conclusion, the implantation of dental pulp constructs into pulp exposed stimulates the formation of calcified dentin-like structures.

Fabrication of HA/TCP scaffolds with a graded and porous structure using a camphene-based freeze-casting method

A room temperature camphene-based freeze-casting method was used to fabricate hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic scaffolds. By varying the solid loading of the mixture and the freezing temperature, a range of structures with different pore sizes and strength characteristics were achieved. The macropore size of the HA/TCP bioceramics was in the range of 100–200 μm, 40–80 μm and less than 40 μm at solid loadings of 10, 20 and 30 vol.%, respectively. The initial level of solid loading played a primary role in the resulting porosity of the scaffolds. The porosity decreased from 72.5 to 31.4 vol.% when the solid loading was increased from 10 to 30 vol.%. This resulted in an increase in the compressive strength from 2.3 to 36.4 MPa. The temperature gradient, rather than the percentage porosity, influenced the pore size distribution. The compressive strength increased from 1.95 to 2.98 MPa when samples were prepared at 4 °C as opposed to 30 °C. The results indicated that it was possible to manufacture porous HA/TCP bioceramics, with compressive strengths comparable to cancellous bone, using the freeze-casting manufacturing technique, which could be of significant clinical interest.

The induction of bone formation by smart biphasic hydroxyapatite tricalcium phosphate biomimetic matrices in the non‐human primate Papio ursinus

Long-term studies in the non-human primate Chacma baboon Papio ursinus were set to investigate the induction of bone formation by biphasic hydroxyapatite/p-tricalcium phosphate (HA/β-TCP) biomimetic matrices. HA/β-TCP biomimetic matrices in a pre-sinter ratio (wt%) of 40/60 and 20/80, respectively, were sintered and implanted in the rectus abdominis and in calvarial defects of four adult baboons. The post-sinter phase content ratios were 19/81 and 4/96, respectively. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices with substantial bone formation by induction and resorption/dissolution of the implanted matrices. One year after implantation in calvarial defects, 4/96 biphasic biomimetic constructs showed prominent induction of bone formation with significant dissolution of the implanted scaffolds. The implanted smart biomimetic matrices induce de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-β(TGF-β) superfamily. The induction of bone formation biomimetizes the remodelling cycle of the cortico-cancellous bone of primates whereby resorption lacunae, pits and concavities cut by osteoclastogenesis are regulators of bone formation by induction. The concavities assembled in HA/β-TCP biomimetic bioceramics are endowed with multifunctional pleiotropic self-assembly capacities initiating and promoting angiogenesis and bone formation by induction. Resident mesenchymal cells differentiate into osteoblastic cell lines expressing, secreting and embedding osteogenic soluble molecular signals of the TGF-β superfamily within the concavities of the biomimetic matrices initiating bone formation as a secondary response.

Creation of New Bone by the Percutaneous Injection of Human Bone Marrow Stromal Cell and HA/TCP Suspensions

The in vivo transplantation assay has become a valuable tool for assessing the osteogenic potential of diverse cell populations. It has required that cells are cotransplanted with a matrix into recipient animals using large incisions and extensive dissections. Here, we demonstrate that transplants of an osteogenic cell population, bone marrow stromal cells (BMSCs), are capable of assembling into mature bone organs when injected as suspensions of cells and a particulate matrix. Human BMSCs, along with hydroxyapatite/tricalcium phosphate (HA/TCP) particles, were placed either into the dorsal subcutaneous space or onto the calvarium of immunodeficient mice, either via injection or via a wide operative exposure. Transplants were harvested from 7 to 110 weeks later; their histologic and mechanical properties and their cellular origin were analyzed. A total of 43 transplants were evaluated. The extent of new bone and hematopoiesis, the bone's adherence to the underlying mouse calvarium, and the bone elastic modulus and hardness were comparable between the two groups. In situ hybridization confirmed a human origin of the new bone. Our data indicate that BMSCs and HA/TCP particles, when injected as a suspension, can assemble into mature bone organs, and that this bone has histologic and mechanical properties similar to bone formed in standard transplants delivered through a large incision. These results open the possibility for assessing the osteogenic capacities of cell populations, for modeling bone formation and repair and for treating bone deficits, all in the context of minimal surgical intervention or soft tissue disruption.

Influence des membranes induites sur l’ostéogenèse hétérotopique au sein d’un complexe ostéo-inducteur. Étude expérimentale chez le lapin

Based on a new concept, a procedure combining induced membranes and cancellous autografts allows the reconstruction of wide diaphyseal defects. To date, this procedure is limited by the amount of cancellous bone available from the patient and by the related morbidity at the donor site. The aim of this study was to evaluate the biological effect of induced membranes on a cylindrical-shaped ceramic implants loaded with OP-1 in heterotopic site. Sixty hydroxyapatite tricalcium phosphate (HA-TCP) implants, 20 of which being loaded with a bone growth factor (rhOP-1) were inserted either in a subcutaneous tunnel or within a previously induced membrane on the back of rabbits. There were two time-points at four and 16 weeks. Implants were investigated at three different levels (extremities and middle). None of the untreated implants showed any evidence of bone formation. Implants inserted in an induced membrane presented with less resorption. Bone ingrowth within the pores of the materials was significantly higher when the implants were inserted into the induced membrane whatever the time-point considered. The membrane seems to play the role it was assigned, i.e. to protect and revascularize the implant, thus favouring osteogenesis that occurs in 80% of the implants after four months.

Bone Morphogenetic Protein (RhBMP-2) as a Substitute for Iliac Crest Bone Graft in Multilevel Adult Spinal Deformity Surgery

Prospective, single center, nonblinded radiographic analysis of anterior and posterior adult spinal deformity fusions performed with bone morphogenetic protein (rhBMP-2). To determine the ability of rhBMP-2 to achieve multilevel spinal fusion in the deformity patient. No previous study has evaluated rhBMP-2 for multilevel adult spinal deformity fusion with 2-year results. We postulated fusion could be achieved without distant autogenous graft harvest. Prospective analysis was performed for 98 patients (308 levels; mean age, 51.4 years) who underwent multilevel anterior or posterior spinal fusion (PSF) with minimum 2-year follow-up (average, 2.6 years). Group 1 (10 mg/level) contained 47 patients (109 levels; 2.33 levels/patient) who underwent anterior spinal fusion (ASF): BMP on an absorbable collagen sponge (ACS) with a titanium mesh cage. Group 2 (20 mg/level) included 43 patients (156 levels; 3.63 levels/patient) with PSF: BMP on an ACS with local bone graft (LBG) and bulking agent [tricalcium phosphate/hydroxyapatite (TCP-HA)]. Group 3 (40 mg/level) contained 8 patients (43 levels; 5.38 levels/patient) with PSF: rhBMP-2 and TCP-HA with no autologous bone. Confounding negative factors were present in the study population: medical comorbidities (26%), tobacco use (17%), revision surgery (34%), previous laminectomy (51%), and preoperative pseudarthrosis (27%). Postoperative films (AP, lateral, oblique) were evaluated by independent observers. Average fusion grade was based on a published scale. Overall fusion rate was 95%. (group 1 91%, group 2 97%, group 3 100%). No confounding factor demonstrated a detrimental statistical significance to fusion. In multilevel ASF, BMP (10 mg/level) generates fusion without autogenous bone. In multilevel PSF, BMP (20 mg/level) with LBG and TCP-HA produced fusion. BMP (40 mg/level) and TCP-HA without LBG achieved fusion. In multilevel spinal fusion, rhBMP-2 eliminated the necessity for iliac crest bone graft and yielded an excellent fusion rate.

Long-term stable canine mandibular augmentation using autologous bone marrow stromal cells and hydroxyapatite/tricalcium phosphate

Transplants of culture-expanded bone marrow stromal cells (BMSCs) combined with hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds successfully form cortico-cancellous bone to reconstruct the dog craniofacial skeleton. Yet, these transplants' long-term stability in large animal models has not been evaluated. This study's purpose was the evaluation of long-term BMSC transplant stability when used to augment the mandible. Here, autologous BMSC–HA/TCP transplants were introduced onto the unilateral dog mandible as onlay grafts, while contralateral control mandibles received HA/TCP onlays alone. Quantitative CT (qCT) scans were obtained both early and late after transplantation. Transplants were harvested up to 19 months later for histologic and mechanical analyses. In all dogs, BMSC transplants formed significantly greater amounts of bone over their control counterparts. The new bone formed an extensive union with the underlying mandible. BMSC transplants retained the majority of their initial volume, while control (HA/TCP only) transplants were nearly completely resorbed. By qCT, the extent of newly formed bone could be determined non-invasively. In summary, HA/TCP particles alone undergo a high degree of resorption, while autologous cultured BMSC–HA/TCP transplants provide long-term bony augmentation of the mandible.

Do we need synthetic osteotomy augmentation materials for opening-wedge high tibial osteotomy

High tibial osteotomy (HTO) is an increasing popular method to treat unicompartimental osteoarthritis of the knee in younger, active patients. In so doing one tries to delay the need for total or unicompartimental joint replacement. The augmentation of HTO opening gaps with supporting material is discussed controversially, especially after the introduction of locking plates, which contribute to the decline of the non-union rate. Currently, we do not recommend synthetic augmentation, when using locking plates in HTO with opening angles less than 10°. In our recent randomized study we could histologically and radiologically demonstrate the complete rebuilding of lamelliform bone in patients without synthetic augmentation, whilst bony ingrowth into the hydroxyapatite/tricalcium phosphate (HA/TCP) wedge of augmented osteotomies just slowly progressed. In contrast to unaugmented osteotomies, there was no advantage in using HA/TCP wedges or the combination of HA/TCP wedges and platelet rich plasma (PRP) as supporting material after 12 months. In osteotomies where an opening angle bigger than 7.5° is chosen, rigid locking plates should be used. In our opinion, autologous iliac crest graft should be used in the high-risk patients (obese, smoker, opening angle bigger than 10°). Whether synthetic augmentation combined with PRP is equal or even superior to autologous iliac crest graft in openings bigger than 10° has not been proven yet.

Dissolution characteristics of extrusion freeformed hydroxyapatite–tricalcium phosphate scaffolds

The dissolution behaviour of calcium phosphate filaments made by extrusion freeforming for hard tissue scaffolds was measured. The solubility of filaments with different HA/beta-TCP ratios sintered at temperatures from 1,100 to 1,300 degrees C was measured under simulated physiological conditions (tris buffer solution: tris(hydroxyl) methyl-aminomethane-HCl), pH 7.4, 37 degrees C). Calcium and phosphate concentrations were measured separately by inductively coupled plasma (ICP) atomic emission spectroscopy. Surface morphologies and composition before and after immersion were analyzed by SEM and EDS. The results clearly show that as the beta-TCP content increased, the dissolution increased. Higher sintering temperatures, with consequent closure of surface pores, resulted in lower dissolution. Examination of the surface suggested dissolution on preferred sites by pitting.

Histomorphometric assessment of bone formation in sinus augmentation utilizing a combination of autogenous and hydroxyapatite/biphasic tricalcium phosphate graft materials: at 6 and 9 months in humans

The aim of this study was to examine the efficacy of a new biphasic hydroxyapatite/tricalcium phosphate (HA/TCP) bone substitute in combination with particulate autogenous bone in sinus floor augmentation procedures. A simultaneous or a two-stage sinus augmentation and implant placement were conducted in 28 patients. A mixture of HA/TCP and autogenous bone chips in a 1 : 1 ratio was used as the grafting biomaterial. Cylindrical specimen bone retrieval was performed in all patients except one. Specimens were harvested either at 6 (n=14) or 9 (n=13) months post-augmentation. For histologic and histomorphometric evaluations, the non-decalcified tissue processing (Donath's technique) was performed. Newly formed bone around the grafted particles was found in all samples. The encircling, highly cellular bone followed the outline of the grafted particles in direct contact. Both woven and lamellar types of bone were observed. Morphometrically, the total mean bone area fraction of all sections was 34.8+/-10.3%, increasing from 28.6+/-7.8% at 6 months to 41.6+/-8.3% at 9 months (P<0.001). Mean particle area fraction average was 25.5+/-11.6% and 23.5+/-9.3% at 6 and 9 months, respectively, with a total mean of 24.5+/-10.4%. The increase in bone area fraction was not significantly correlated to the decrease of the grafted particles area fraction. The biphasic HA/TCP showed biocompatible and osteoconductive properties. This alloplast as a composite with autogenous bone chips promotes newly formed bone, which increases in its fraction along an extended healing period.

Histomorphometric assessment of bone formation in sinus augmentation utilizing a combination of autogenous and hydroxyapatite/biphasic tricalcium phosphate graft materials: at 6 and 9 months in humans

AbstractObjective: The aim of this study was to examine the efficacy of a new biphasic hydroxyapatite/tricalcium phosphate (HA/TCP) bone substitute in combination with particulate autogenous bone in sinus floor augmentation procedures.Material and methods: A simultaneous or a two‐stage sinus augmentation and implant placement were conducted in 28 patients. A mixture of HA/TCP and autogenous bone chips in a 1 : 1 ratio was used as the grafting biomaterial. Cylindrical specimen bone retrieval was performed in all patients except one. Specimens were harvested either at 6 (n=14) or 9 (n=13) months post‐augmentation. For histologic and histomorphometric evaluations, the non‐decalcified tissue processing (Donath's technique) was performed.Results: Newly formed bone around the grafted particles was found in all samples. The encircling, highly cellular bone followed the outline of the grafted particles in direct contact. Both woven and lamellar types of bone were observed.Morphometrically, the total mean bone area fraction of all sections was 34.8±10.3%, increasing from 28.6±7.8% at 6 months to 41.6±8.3% at 9 months (P&lt;0.001). Mean particle area fraction average was 25.5±11.6% and 23.5±9.3% at 6 and 9 months, respectively, with a total mean of 24.5±10.4%. The increase in bone area fraction was not significantly correlated to the decrease of the grafted particles area fraction.Conclusions: The biphasic HA/TCP showed biocompatible and osteoconductive properties. This alloplast as a composite with autogenous bone chips promotes newly formed bone, which increases in its fraction along an extended healing period.

In vitro study of matrix surface properties of porous granulated calcium phosphate ceramic materials made in Russia

We performed in vitro screening of monophasic (hydroxyapatite, beta-tricalcium phosphate, carbonate-substituted hydroxyapatite with 0.59 and 5.9 wt% substitution with CO(3)(2-)) and biphasic (hydroxyapatite-tricalcium phosphate with various percentage of the components 80/20, 60/40, 20/80, silicon-substituted hydroxyapatite with 0.79 wt% SiO(2)) porous granulated ceramics composed of calcium phosphate powders synthesized by methods of heterophasic interaction of reagents and precipitation from aqueous solutions using MTT test and cultured human fibroblasts. Acute toxicity of materials (24-h incubation with cell culture) and matrix properties (3, 5, 7, 14, 18, 21, 28 days in culture) were evaluated. We selected a batch of materials obtained by precipitation from aqueous solutions, which were non-toxic and were characterized by good matrix properties (for cells). Biphasic ceramics with hydroxyapatite-tricalcium phosphate ratio of 80/20 exhibited best characteristics, and ceramics on the basis of silicon-substituted hydroxyapatite showed moderate characteristics.

Histologic Analysis of Allograft Mixed With Hydroxyapatite-Tricalcium Phosphate Used in Revision Femoral Impaction Bone Grafting

Failed total hip arthroplasty (THA) often is accompanied by loss of bone stock. In cases in which revision THA becomes necessary, adequate stabilization of the implant can be difficult because of the bone loss. Bone can be reconstructed by using tightly packed morselized cancellous bone graft in combination with a cemented stem. However, worldwide availability of human bone is limited, and risks such as infection and antigenicity are associated with the use of allogeneic bone. These risks have led to the development of synthetic bone graft extenders. The objective of impaction bone grafting is to achieve stability of an implant and subsequently allow the restoration of living bone stock. To reduce the amount of allograft consumed, a mixture of morselized allograft and hydroxyapatite-tricalcium phosphate was used for impaction grafting in a series of 15 patients. In 2 patients who required re-revision arthroplasty, the areas of impacted graft were analyzed histologically. The results showed a complex mixture of residual hydroxyapatite-tricalcium phosphate, necrotic bone (graft), viable bone, and fibrous tissue. Although several pre-clinical studies have described the expansion of allograft with synthetic materials, this article represents the first description of histologic findings in human femoral impaction grafting with a combination of allograft and hydroxyapatite-tricalcium phosphate.

Reconstruction of Cranial Bone Defects Using a Compound of Bone Marrow Stromal Cells and Hydroxyapatite-Tricalcium Phosphate

Hydroxyapatite-tricalcium phosphate (HA-TCP) is a new kind of material which shows good biocompatibility, biological degradability, and porosity. This study aimed to determine the effectiveness of HA-TCP as a bone tissue engineering scaffold. In this study, critical size cranial defects were reconstructed with compounds of autogenous bone marrow stromal cells (BMSCs) and HA-TCP. The resulting grafts were examined by X-ray, histological examination, semi-quantitative analysis of osteogenesis, immunochemical examination (collagen type I and III), scanning electron microscopy and transmission electron microscopy. The results showed that HA-TCP is a good bone tissue engineering scaffold and BMSCs/HA-TCP is a promising technique for reconstruction of bone defects.

Bone morphogenetic protein‐2 enhances bone formation when delivered by a synthetic matrix containing hydroxyapatite/tricalciumphosphate

The aim of the present study was to test whether or not a synthetic matrix consisting of a polyethylene glycol (PEG) hydrogel containing recombinant human bone morphogenetic protein-2 (rhBMP-2) combined with grafting materials enhances bone regeneration compared with grafting alone or empty control sites. In each of 10 rabbits, four titanium cylinders were screwed in perforated slits made in the external cortical bones of the calvaria. The following four treatment modalities were randomly allocated: (1) empty control, (2) a combination of a PEG matrix and hydroxyapatite/tricalciumphosphate (HA/TCP) granules and a combination of a PEG matrix containing either 10 microg/ml (3) or 30 microg/ml (4) of BMP-2 and HA/TCP granules. After 8 weeks, the animals were sacrificed and ground sections were obtained for histological analysis. For statistical analysis repeated measures ANOVA and subsequent pairwise Student's t-test were applied (P<0.01). Histomorphometric analysis showed an average area fraction of newly formed bone of 13.96+/-5.98% for the empty control, 15.16+/-7.95% for the PEG and HA/TCP group, 26.32+/-8.56% for the group containing 10 mug rhBMP-2/ml, and 30.15+/-7.63% for the group containing 30 microg rhBMP-2/ml. Statistical analysis revealed significantly more newly formed bone in the two rhBMP-2 groups compared with the PEG and HA/TCP group and with the empty control. Regarding the surface fraction of the HA/TCP graft particles covered with newly formed bone the addition of rhBMP-2 revealed a more than two-fold increase compared with cylinders containing HA/TCP granules without rhBMP-2. This difference reached statistical significance. It is concluded that rhBMP-2 significantly enhances bone regeneration in rabbits when delivered by a synthetic matrix containing HA/TCP. This synthetic PEG matrix containing HA/TCP granules apparently fulfills a number of criteria required for an ideal carrier system for rhBMP-2.

Biomimetic Smart Hydroxyapatite/Biphasic Tricalcium Phosphate Biomatrices Induce Bone Formation

Long-term studies in the non-human primate Papio ursinus were set to investigate the induction of bone formation in biphasic hydroxyapatite tricalcium phosphate (HA/TCP) biomimetic matrices, 20/80 and 40/60, respectively. Biomimetic matrices were implanted in the rectus abdominis and in calvarial defects of 4 adult Papio ursinus. Morphological analyses on day 90 and 365 showed significant induction of bone formation within concavities of the biomimetic matrices implanted in both heterotopic and orthotopic sites with resorption of the implanted biomimetic matrices. The smart biomimetic matrices induced de novo bone formation even in the absence of exogenously applied osteogenic proteins of the transforming growth factor-β superfamily.

Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone

Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering.