Evaluation of DBM/AM composite as a graft substitute for posterolateral lumbar fusion

Demineralized bone matrix (DBM) has been investigated as a bone graft substitute for spinal fusion with less morbidity. Various carriers have been added to DBM to enhance its handling characteristics. This study investigates the spinal fusion induced by a composite of DBM and acellular dermal matrix (AM) in comparison with autologous bone in an athymic rat spinal fusion model. Single-level intertransverse process fusions were performed in 60 athymic nude rats grafted with 2 mL/kg of DBM/AM composite, AM alone, or autologous bone. Fusion was assessed at 6 weeks by radiography, manual palpation, and histology. At 6 weeks, 70% of the animals from the DBM/AM composite group exhibited complete spine fusion, whereas 35% from the autologous bone group and 20% from AM group showed bridging with some gaps. The DBM/AM composite induced a significantly higher fusion rate than both the autologous bone and AM groups (p < 0.001) in all measured parameters. The current study demonstrated that using DBM/AM composite can have more robust fusion than autologous bone at 6 weeks in an athymic rat spinal fusion model.     

Calcium sulfate-carboxymethylcellulose bone graft binder: Histologic and morphometric evaluation in a critical size defect

Calcium sulfate (CS) is widely used as a bone graft binder and expander. Recent reports indicate that carboxymethylcellulose (CMC) can improve the clinical properties of CS when used as binder for particulate bone grafts; however, limited information is available on the effects of CMC on bone regeneration. The purpose of this study was to evaluate the histologic and morphometric characteristics of bone formation in calvarial defects grafted with a CS-based putty containing 10% CMC in combination with allogeneic demineralized bone matrix (DBM). Bone formation and graft/binder resorption were compared with a surgical grade CS and DBM in paired critical-sized calvarial defects in 25 Wistar rats (350-450 g). Six animals each provided paired defects at 7, 14, 21, and 28 days postsurgery for nondecalcified processing and microscopic analysis. Defects grafted with CS or CS-CMC putty as the DBM binder exhibited similar patterns and proportions of bone formation, fibrous tissue/marrow, and residual DBM particles. Comparable mean +/- SD proportions of new bone formation (31.7 +/- 9.5 and 33.7 +/- 12.9), fibrous tissue/marrow (54.2 +/- 8.3 and 53.0 +/- 10.8), residual DBM particles (8.3 +/- 6.8 and 10.1 +/- 6.3), and residual binder material (5.5 +/- 4.6 and 3.7 +/- 3.5) were found at 28 days for defects grafted with CS and CS-CMC putty, respectively. Thus, CMC was found to improve the handling characteristics of CS and, when used in conjunction with DBM, supported comparable levels bone formation and patterns of binder/scaffold resorption as CS and DBM in a calvarial defect model.     

Effects of gamma-irradiation, storage and hydration on osteoinductivity of DBM and DBM/AM composite

This study investigated the effect of gamma-irradiation dose, irradiation temperature, hydration and storage condition on osteoinductivity of demineralized bone matrix (DBM) and demineralized bone matrix/acellular dermal matrix (DBM/AM) composite. DBM and DBM/AM in dry and hydrated form were treated with gamma-irradiation of 15-40 kGy at ambient or low temperature (-40 degrees C approximately -70 degrees C) and then stored at ambient condition for 6 months. The athymic rat muscle implant model was used to evaluate the osteoinductive potential of the DBM and DBM/AM composites. Histological and alkaline phosphatase (ALPase) activity assessments were carried out at 28 days after implantation to determine the new bone formation and ALPase activity. Both histological and ALPase activity analysis showed that the osteoinductivity of DBM decreased with the increase of gamma-irradiation dose at ambient temperature, whereas no decrease occurred when treated with gamma-irradiation at low temperature. However, the hydrated DBM showed diminishing osteoinductivity after 6-month storage at ambient condition, whereas the DBM in dry form retained their osteoinductivity after the 6-months storage. The findings in this study indicate that DBM and DBM/AM composites could retain their osteoinductivity when they are in dry configuration and are irradiated at low temperature (-40 degrees C approximately -70 degrees C) using the custom-made cold gamma-irradiation system.     

Calvarial bone response to a tricalcium phosphate-genipin crosslinked gelatin composite

A biodegradable composite which was composed of genipin cross-linked gelatin mixing with tricalcium phosphate ceramic particles (GGT) was developed as a bone substitute. This study was evaluated by the biological response of rabbit calvarial bone to assess the potential of the GGT composite as a biodegradable and osteoconductive bone substitute. Eighteen New Zealand white rabbits were used for cranial implantation. Bone defects (15 x 15 mm) of nine rabbits were filled with the GGT composites, while the others were filled with the de-proteinized bovine bones as controls. Three rabbits were examined for each group in every time period at 4, 8 and 12 weeks post-surgery. The assessment included serial post-operative gross examinations, radiographic analyses and histological evaluations. This study demonstrated that this composite is: (1) malleable, with easily molded to the calvarial bone defect without fracture; (2) biocompatible, with no evidence of adverse tissue reaction; (3) osteoconductive, with progressive growth of new bone into the calvarial bone defect; (4) biodegradable, with progressive replacement of the composite by new bone. Additionally, results of both radiographic analyses and histological evaluations revealed obviously greater new bone ingrowth in the GGT composite compared with the de-proteinized bovine bone at the same implantation time. Therefore, the GGT composite could serve as a useful bone substitute for repairing bone defects.     

Bone formation in calvarial defects of Sprague-Dawley rats by transplantation of calcium phosphate glass

The purpose of this study was to investigate the bone-regenerative effect of calcium phosphate glass in vivo. We prepared amorphous calcium phosphate glass powder having a mean particle size of 400 microm in the system CaO-CaF2-P2O5-MgO-ZnO. Calvarial critical-sized defects (8 mm) were created in 60 male Sprague-Dawley rats. The animals were divided into an experimental group and control group of 30 animals each. Each defect was filled with a constant weight of 0.5 g calcium phosphate glass powder mixed with saline. As a control, the defect was left empty. The rats were sacrificed 2, 4, or 8 weeks postsurgery, and the results evaluated using radiodensitometric and histological studies; they were also examined histomorphometrically. When the calcium phosphate glass powders with 400-microm particles were grafted, the defects were nearly completely filled with new-formed bone in a clean healing condition after 8 weeks. It was observed that the prepared calcium phosphate glass enhanced new bone formation in the calvarial defect of Sprague-Dawley rats and could be expected to have potential for use as a hard tissue regeneration material.     

Histological evaluation of an impacted bone graft substitute composed of a combination of mineralized and demineralized allograft in a sheep vertebral bone defect

Demineralized bone matrix (DBMs) preparations are a potential alternative or supplement to autogenous bone graft, but many DBMs have not been adequately tested in clinically relevant animal models. The aim of current study was to compare the efficacy of a new bone graft substitute composed of a combination of mineralized and demineralized allograft, along with hyaluronic acid (AFT Bone Void Filler) with several other bone graft materials in a sheep vertebral bone void model. A drilled defect in the sheep vertebral body was filled with either the new DBM preparation, calcium sulfate (OsteoSet), autologous bone graft, or left empty. The sheep were euthanized after 6 or 12 weeks, and the defects were examined by histology and quantitative histomorphometry. The morphometry data were analyzed by one-way analysis of variance with the post hoc Tukey-Kramer test or the Student's t-test. All of the bone defects in the AFT DBM preparation group showed good new bone formation with variable amounts of residual DBM and mineralized bone graft. The DBM preparation group at 12 weeks contained significantly more new bone than the defects treated with calcium sulfate or left empty (respectively, p < 0.05, p < 0.01). There was no significant difference between the DBM and autograft groups. No adverse inflammatory reactions were associated with any of the three graft materials. The AFT preparation of a mixture of mineralized and demineralized allograft appears to be an effective autograft substitute as tested in this sheep vertebral bone void model.     

The influence of FDBA and autogenous bone particles on regeneration of calvaria defects in the rabbit: A pilot study

The histological behavior of bone formation using three biomaterials was examined including whether an 8 mm rabbit calvarial defect would behave as a critical size defect. Four trephine defects of 8 mm diameter in were created six rabbit parietal bones. A control defect was maintained only with coagulum and others were filled with autologous bone, FDBA (freeze dried bone allograft) and a mixture of autologous bone with FDBA, respectively. The animals were sacrificed after between 15 and 90 days at intervals of two weeks and the extracted samples were processed for histological evaluation. All control defects showed incomplete bone formation during 90 days of observation. The defects filled with FDBA and mixture of FDBA-autologous bone exhibited a higher regeneration degree than autologous bone after 60 days; however, the only biomaterial revealing complete mineralization of the original defect at 90 days was FDBA. In conclusion, 8 mm defects can be considered as critical size defects and only FDBA showed mature lamellar bone at 90 days.     

Effect of acellular dermal matrix as a delivery carrier of adipose-derived mesenchymal stem cells on bone regeneration

The purpose of this study is to evaluate the effect of acellular dermal matrix (ADM) as a delivery carrier of adipose-derived mesenchymal stem cells (ASCs) on bone regeneration in athymic murine calvarial bone defect. Paired-critical size defects in nude rat skull were made. The right-side defects received ASCs/ADM or only ADM, whereas the left-side defect was not treated. In 3D images, new bone formation in the ASCs/ADM group was apparent at 4 wk, but in the ADM group at 8 wk. At 4 and 8 wk, bone mineral density and tissue volume in rats that received ASCs/ADM were significantly greater than rats that received ADM and control groups. Histological examination revealed that the defect was repaired by bone in the ASCs/ADM group, whereas only minimal bone island with fibrous connection was observed in the control group. In histomorphometric analysis, the total healing score in the ASCs/ADM group at 4 wk was significantly higher than the ADM and negative control group, whereas the score of 8 wk was similar between the ASCs/ADM and ADM group. ASCs/ADM implants promote new bone formation more rapidly than ADM only or no treatment. ADM seeded with ASCs may be potentially useful as a future biomaterial option in bone implants.     

Reconstruction of critical size calvarial bone defects in rabbits with glass-fiber-reinforced composite with bioactive glass granule coating

The aim of this study was to evaluate glass-fiber-reinforced composite as a bone reconstruction material in the critical size defects in rabbit calvarial bones. The bone defect healing process and inflammatory reactions were evaluated histologically at 4 and 12 weeks postoperatively. Possible neuropathological effects on brain tissue were evaluated. The release of residual monomers from the fiber-reinforced composite (FRC) was analyzed by high performance liquid chromatograph (HPLC). RESULTS: At 4 weeks postoperatively, fibrous connective tissue ingrowth to implant structures was seen. Healing had started as new bone formation from defect margins, as well as woven bone islets in the middle of the defect. Woven bone was also seen inside the implant. Inflammation reaction was slight. At 12 weeks, part of the new bone had matured to lamellar-type, and inflammation reaction was slight to moderate. Control defects had healed by fibrous connective tissue. Histological examinations of the brain revealed no obvious damage to brain morphology. In HPLC analysis, the release of residual 1,4-butanedioldimethacrylate and methylmethacrylate from polymerized FRC was low. CONCLUSIONS: This FRC-implant was shown to promote the healing process of critical size calvarial bone defect in rabbits. After some modifications to the material properties, this type of implant has the potential to become an alternative for the reconstruction of bone defects in the head and neck area in the future.     

Performance of hydroxyapatite bone repair scaffolds created via three-dimensional fabrication techniques

The current study analyzes the in vivo performance of porous sintered hydroxyapatite (HA) bone repair scaffolds fabricated using the TheriForm solid freeform fabrication process. Porous HA scaffolds with engineered macroscopic channels had a significantly higher percentage of new bone area compared with porous HA scaffolds without channels in a rabbit calvarial defect model at an 8-week time point. An unexpected finding was the unusually large amount of new bone within the base material structure, which contained pores less than 20 microm in size. Compared with composite scaffolds of 80% polylactic-co-glycolic acid and 20% beta-tricalcium phosphate with the same macroscopic architecture as evaluated in a previous study, the porous HA scaffolds with channels had a significantly higher percentage of new bone area. Therefore, the current study indicates that scaffold geometry, as determined by the fabrication process, can enhance the ability of a ceramic material to accelerate healing of calvarial defects.     

Evaluation of the biocompatibility and osteoproductive activity of ostrich eggshell powder in experimentally induced calvarial defects in rabbits

The purpose of this study was to investigate the beneficial effects of particulate ostrich eggshell grafting on the healing of experimentally induced skull defects. The clinical, radiological, histological, and histomorphometrical findings of this material were compared with the results of commercially available demineralized bone matrix (DBM). The study was conducted on 18 adult New Zealand rabbits. One defect served as a control and the remaining ones either were filled with different sized eggshell particles or DBM, in each animal. Clinical and radiological inspections and histologic investigations of the animals were done at the 1st, 3rd, and 6th months of postoperative period. Radiologically, minimal bone regeneration was observed at the empty, control defect sites. The most advanced bone regeneration was in the DBM grafted defects. The eggshell particle grafted defect sites displayed weak bone regeneration at earlier stages, at 1st and 3rd months after operation when compared with demineralized bone matrix. Nevertheless, ossification was satisfactory at 6th month after operation when compared with the control defects. Within the limitations of this study, it was concluded that Ostrich eggshell powder (OSP) is a worth-while bone substitute because it is a safe, cheap, and easily available material. Long-term studies will clarify its possible role in maxillofacial surgery. Further sophisticated experiments should be undertaken before human implantation concerning its osteoproductive activity alone or in combination with other materials.     

Bone grafts cultured with bone marrow stromal cells for the repair of critical bone defects: an experimental study in mice

Tissue engineering of autologous bone combined with osteoprogenitor cells is a suitable strategy for filling large bone defects. The aim of this study was to evaluate the osteogenicity of a xenogenic bone graft cultured with allogenic bone marrow stromal cells (BMSC) in a mouse critical size craniotomy. Bovine trabecular bone grafts were made free of bone marrow cells or debris and were delipidated. BMSC were harvested from C57BL/6-Tg(ACTbEGFP)1Osb/J mice (GFP+ cells) and were cultured 14 days on bone grafts in control or osteogenic medium. Engineered grafts were implanted in calvarial defect in C57BL/6 mice. Four groups were studied: graft with BMSC differentiated in osteoblasts (G-Ob), graft with BMSC (G-BMSC), graft without cells (G) and no graft. Calvariae were studied 2 and 8 weeks after implantation by radiographic and histomorphometric analyses. G group: the bone ingrowth was limited to the edges of the defect. The center of the graft was filled by a fibrovascular connective tissue. G-BMSC or G-Ob groups: bone formation occurred early in the center of the defect and did not increase between 2 and 8 weeks; the newly formed woven bone was partially replaced by lamellar bone. The preoperative osteoblastic differentiation of BMSC did not allow faster and better bone regeneration. After 2 weeks, GFP+ cells were observed around the grafted bone but no GFP+ osteocyte was present in the newly formed bone. No GFP+ cell was noted after 8 weeks. However, pre-implantation culture of the biomaterial with allogenic BMSC greatly enhanced the bone regeneration.     

Increased new bone formation with a surface magnesium-incorporated deproteinized porcine bone substitute in rabbit calvarial defects

This study investigated the effects of magnesium ion (Mg) incorporation into the surface of deproteinized porcine cancellous bone in the bone healing of rabbit calvarial defects with the expectation of utilizing the integrin-ligand binding enhancement effect of Mg, and compared its bone healing capacity with that of untreated porcine cancellous bone and deproteinized bovine bone (Bio-Oss). Hydrothermal treatment was performed to produce Mg-incorporated porcine bone using an alkaline Mg-containing solution. The surface morphology and chemical composition of the samples were investigated using scanning electron microscopy, energy-dispersive X-ray spectrometry, and X-ray photoelectron spectroscopy. Defects 7 mm in diameter were created in the calvaria of 14 adult male New Zealand White rabbits and were filled with (1) untreated porcine bone (PB), (2) Bio-Oss, and (3) Mg-containing porcine bone (MG). The percentage of newly formed bone (NB%) was evaluated histomorphometrically at 2 and 4 weeks after implantation. Hydrothermal treatment resulted in a Mg-containing surface in porcine bone covered with nanostructures ~100 nm in size. The MG group supported better new bone formation compared with the other groups. Osteoconductive new bone formation was observed in the central defect area in the MG group at an early healing time-point. Histomorphometric analysis revealed significantly greater NB% in the MG group when compared with the untreated PB and Bio-Oss groups at 4 weeks (p < 0.05). The Mg-incorporated porcine bone with surface nanostructures achieved rapid new bone formation in the osseous defects of rabbit calvaria compared with untreated xenografts of porcine and bovine origin.     

BMP-2 incorporated in a tricalcium phosphate bone substitute enhances bone remodeling in sheep

Bone morphogenetic protein-2 (BMP-2) is a well-known osteoinductive protein, which requires a carrier for local application. As an alternative to the previously described carriers, an in situ hardening, resorbable, and osteoconductive beta-tricalcium phosphate cement (TCP) is tested. Trepanation defects in the bovine distal femoral epiphysis are filled with a composite consisting of TCP and 200 microg rhBMP-2 per cm3 TCP, autologous bone graft, pure TCP, or left empty. A radiological follow-up is performed after 7 weeks and 3 months. The sheep are euthanized and bone samples are analyzed by microradiography, histology, and histomorphometry. Microradiography and histology show similar results for pure TCP and the composite. The defects are filled with trabecular bone and newly formed bone is in close contact with the remaining TCP-particles. The majority of the cement is resorbed, in the composite group the amount of remaining cement particles is reduced. Defects treated with autologous bone graft are filled completely, while untreated defects shows only a small amount of bone originating from the rim of the defect. Histomorphometry of the defects treated with pure TCP shows a significantly increased bone content in comparison to defects treated with the composite or autologous bone graft. Analysis of the remaining cement particles shows significantly less cement in the TCP/rhBMP-2 group in comparison to pure TCP. The sum of bone and cement content in the rhBMP-2 group shows amounts comparable to the calcified structures found following autologous bone grafting. The addition of rhBMP-2 to the TCP leads to faster remodeling of the defect comparable to autologous bone graft, while defects treated with pure TCP are not completely remodeled.     

The effect of a fibrin-fibronectin/beta-tricalcium phosphate/recombinant human bone morphogenetic protein-2 system on bone formation in rat calvarial defects

In spite of good prospects for bone morphogenetic proteins (BMP) applications, an ideal carrier system for BMPs has not yet been identified. The purpose of this study was to evaluate the osteogenic effect of a fibrin-fibronectin sealing system (FFSS) combined with beta-tricalcium phosphate (beta-TCP) as a carrier system for recombinant human bone morphogenetic proteins (rhBMP-2) in the rat calvarial defect model. Eight-millimeter critical-size calvarial defects were created in 100 male Sprague-Dawley rats. The animals were divided into five groups of 20 animals each. The defects were treated with rhBMP-2/FFSS, rhBMP-2/FFSS/beta-TCP, FFSS and FFSS/beta-TCP carrier control or were left untreated as a sham-surgery control. Defects were evaluated by histologic and histometric parameters following a 2- and 8-week healing interval (10 animals/group/healing intervals). The FFSS/beta-TCP carrier group was significantly greater in new bone area at 2 weeks (p<0.05) and new tissue area at 2 and 8 weeks (p<0.01) relative to the FFSS carrier group. New bone and new tissue area in the rhBMP-2/FFSS/beta-TCP group were significantly greater than in the rhBMP-2/FFSS group at 8 weeks (p<0.01). On histologic observation, FFSS remnants were observed at 2 weeks, but by 8 weeks, the FFSS appeared to be completely resorbed. rhBMP-2 combined with FFSS/beta-TCP produced significantly more new bone and new tissue formation in this calvarial defect model. In conclusion, FFSS/beta-TCP may be considered as an available carrier for rhBMP-2.     

Injectable thermosensitive PEG–PCL–PEG hydrogel/acellular bone matrix composite for bone regeneration in cranial defects

We have certified that the injectable thermosensitive ABM/PECE composite presented promising potential in bone regeneration benefited from the incorporation of the intrinsic osteoinductive acellular bone matrix (ABM) granules into the poly(ethylene glycol)–poly(ε-capro-lactone)–poly(ethylene glycol) (PEG–PCL–PEG, PECE) hydrogel. In this study, the 12 mm × 8 mm × 2 mm cranial defects of the New Zealand white rabbits were fabricated to evaluate the bone regeneration effect. The ABM/PECE composite was injected into the defect while the pure PECE as control, and the bone regeneration was evaluated at 4, 12 and 20 weeks post-surgery by X-radiological examination, micro-computed tomography examination and histological analysis. In ABM/PECE composite treated group, the new bone formed originally from both the margin and the center of the defect, and the defect region had healed up to 20 weeks. Furthermore, the shadow density of the newly formed bone eventually approximated to host cortical bone. In comparison, the control group was filled with sparing new bone with low-density only from the periphery of the defect. Meanwhile, the quantitative determination of new bone by histomorphometry confirmed the excellent bone regeneration of ABM/PECE composite. All the results suggested that the ABM/PECE composite presented enhanced bone regeneration guidance in rabbit cranial defects.     

Evaluation of a resorbable, in situ setting bone substitute in a sheep model

The gold standard for bone substitution is the autologous bone graft, but because of its limited supply and the associated morbidity, the search for synthetic alternatives is necessary. A new in situ setting tricalcium phosphate cement was implanted in a trepanation defect (9.4 mm diameter, 10 mm depth) in the distal femoral epiphysis of sheep. Empty cavities and autologous bone graft were used as controls. Histologic and histomorphometric examinations were carried out after 12 weeks. Nearly 90% of the implanted cement was resorbed and replaced by ingrown bone with close contact between surrounding bone, new bone, and remaining cement particles. The amount of bone in the defect area was significantly higher in defects filled with cement relative to defects filled with autologous bone graft (mean 27 vs. 21%, 95% confidence intervals 23 to 31 and 18 to 23, p = 0.026). In conclusion, this new in situ setting cement is bioactive, resorbable, and osteoconductive. It will be useful as an alternative to autologous bone graft to fill stable defects.     

Demineralized bone matrix as a biological scaffold for bone repair

Experimental models were created in rat fibula to represent impaired bone healing so that biological deficiencies that cause bone repair to fail or to be delayed may be investigated. These models consist of a 4-mm-long segmental defect, created in rat fibula by osteotomy, and fitted with a 7-mm-long tubular specimen of demineralized bone matrix (DBM) over the cut ends of the fibula. The experiments in this study involved various modifications of the DBM scaffold designed to reduce its osteoinductive activity: steam sterilization (sDBM), ethylene oxide sterilization (eoDBM), trypsin digestion (tDBM), and guanidine hydrochloride extraction (gDBM). Bone healing was evaluated by bending rigidity of the fibula and mineral content of the repair site at 7 weeks post-surgery. The sDBM scaffolds resorbed completely by 7 weeks and hence this model was a nonhealing negative control. Rigidities in the unmodified DBM and tDBM groups were comparable, whereas in the gDBM and eoDBM groups it was significantly reduced. Histologically, in the 4-mm defects repaired with unmodified DBM, direct and endochondral bone formation in the scaffold and the defect resulted in a neocortex consisting of woven and lamellar bone uniting the broken bone by 7 weeks post-surgery. We conclude that the eoDBM and gDBM groups represent failure or delay of the bone repair process when compared with the unmodified DBM group in which the process is analogous to normal bone healing.     

The expression of bone matrix proteins induced by different bioimplants in a rabbit sinus lift model

This study aimed to analyze the expression of bone matrix proteins and CD31 by immunohistochemistry after maxillary sinus grafting with different bioimplants in a rabbit model. Rabbit demineralized bone matrix (DBM), partially purified bovine bone morphogenetic proteins (BMP), a mixture of BMP with DBM (BMP/DBM), or particulated autogenous bone was grafted into the maxillary sinuses of 42 rabbits. Animals were sacrificed at 2 and 8 weeks. Immunohistochemistry was used to investigate the expression of type 1 collagen (COL1), osteonectin (ON), osteocalcin (OC), bone sialoprotein (BSP), osteopontin (OPN), and CD31. Sinuses grafted with BMP were filled with trabeculae of woven bone that was strongly immunoreactive for COL1, OC, ON, and BSP. BMP/DBM showed strongly positive immunoreactivity for these proteins within the newly formed bone, but weak immunoreactivity in the DBM particles. Immunoreactivity for COL1, OC, ON, and BSP in DBM sinuses was only seen in the osteoblasts rimming the grafted bone particles. The staining of autogenous bone graft sinuses was similar to those grafted with DBM. OPN staining was detected in autogenous bone graft, BMP/DBM, and BMP bioimplants. CD31 staining was strongest in BMP and BMP/noncollagenous matrix proteins sinuses. These results suggest that exogenous BMP enhances not only osteogenesis but also angiogenesis, an important part of bone repair.     

Performance of degradable composite bone repair products made via three-dimensional fabrication techniques

This study analyzed the in vivo performance of composite degradable bone repair products fabricated using the TheriForm process, a solid freeform fabrication (SFF) technique, in a rabbit calvarial defect model at 8 weeks. Scaffolds were composed of polylactic-co-glycolic acid (PLGA) polymer with 20% w/w beta-tricalcium phosphate (beta-TCP) ceramic with engineered macroscopic channels, a controlled porosity gradient, and a controlled pore size for promotion of new bone ingrowth. Scaffolds with engineered macroscopic channels and a porosity gradient had higher percentages of new bone area compared to scaffolds without engineered channels. These scaffolds also had higher percentages of new bone area compared to unfilled control defects, suggesting that scaffold material and design combinations could be tailored to facilitate filling of bony defects. This proof-of-concept study demonstrated that channel size, porosity, and pore size can be controlled and used to influence new bone formation and calvarial defect healing.