Viable Bone Graft Research Articles

Radiographical outcomes of a cellular based allograft following foot/ankle arthrodesis in patients with risk for non-union.

Morbidity associated with autograft harvest has led to the need for alternative bone grafts during fusion surgical procedures. The purpose of this study is to evaluate the efficacy of a cellular bone allograft (CBA) in patients who underwent foot/ankle fusion surgery. Retrospective data of patients who underwent foot/ankle arthrodesis using a CBA between XXXX and XXXX were collected from a single site. Patients were at least 18 years of age at the time of surgery and had ankle/foot surgery with Trinity ELITE CBA as the primary or only bone graft. Patients' radiographic union was assessed at three (3) months, six (6) months, nine (9) months, and twelve (12) months. Twenty-two (22) patients and 29 joints were evaluated. The mean age and BMI of the cohort were 54±9yrs and 30.5±6kg/m2, respectively. The surgical indications were degenerative joint diseases, trauma, and arthritis. All patients except one had at least one risk factor for non-union. At 12 months, 21 of the 22 patients (95%) attained successful fusion with an average time of 6 months. In addition, there was a 100% fusion among patients with prior failed fusion, nicotine use, diabetes, neuropathy, and osteoporosis. There was no significant difference in time to fusion between patients with non-union risk factor(s) ≤ 1 and ≥ 2 (p=0.71). No complication or adverse event was reported following the surgery. The use of CBA resulted in high fusion among patients with the risk of non-union. CBA is a viable bone graft substitute for autograft in foot/ankle arthrodesis procedures.

Suitability of Gelatin Methacrylate and Hydroxyapatite Hydrogels for 3D-Bioprinted Bone Tissue.

Complex bone defects are challenging to treat. Autografting is the gold standard for regenerating bone defects; however, its limitations include donor-site morbidity and increased surgical complexity. Advancements in 3D bioprinting (3DBP) offer a promising alternative for viable bone grafts. In this experiment, gels composed of varying levels of gelatin methacrylate (GelMA) and hydroxyapatite (HA) and gelatin concentrations are explored. The objective was to increase the hydroxyapatite content and find the upper limit before the printability was compromised and determine its effect on the mechanical properties and cell viability. Design of Experiments (DoE) was used to design 13 hydrogel bioinks of various GelMA/HA concentrations. These bioinks were assessed in terms of their pipettability and equilibrium modulus. An optimal bioink was designed using the DoE data to produce the greatest stiffness while still being pipettable. Three bioinks, one with the DoE-designed maximal stiffness, one with the experimentally defined maximal stiffness, and a literature-based control, were then printed using a 3D bioprinter and assessed for print fidelity. The resulting hydrogels were combined with human bone-marrow-derived mesenchymal stromal cells (hMSCs) and evaluated for cell viability. The DoE ANOVA analysis indicated that the augmented three-level factorial design model used was a good fit (p < 0.0001). Using the model, DoE correctly predicted that a composite hydrogel consisting of 12.3% GelMA, 15.7% HA, and 2% gelatin would produce the maximum equilibrium modulus while still being pipettable. The hydrogel with the most optimal print fidelity was 10% GelMA, 2% HA, and 5% gelatin. There were no significant differences in the cell viability within the hydrogels from day 2 to day 7 (p > 0.05). There was, however, a significantly lower cell viability in the gel composed of 12.3% GelMA, 15.7% HA, and 2% gelatin compared to the other gels with a lower HA concentration (p < 0.05), showing that a higher HA content or print pressure may be cytotoxic within hydrogels. Extrusion-based 3DBP offers significant advantages for bone-tissue implants due to its high customizability. This study demonstrates that it is possible to create printable bone-like grafts from GelMA and HA with an increased HA content, favorable mechanical properties (145 kPa), and a greater than 80% cell viability.

Surface-Modified Piezoelectric Copolymer Poly(vinylidene fluoride-trifluoroethylene) Supporting Physiological Extracellular Matrixes to Enhance Mesenchymal Stem Cell Adhesion for Nanoscale Mechanical Stimulation.

There is an unmet clinical need to provide viable bone grafts for clinical use. Autologous bone, one of the most commonly transplanted tissues, is often used but is associated with donor site morbidity. Tissue engineering strategies to differentiate an autologous cell source, such as mesenchymal stromal cells (MSCs), into a potential bone-graft material could help to fulfill clinical demand. However, osteogenesis of MSCs can typically require long culture periods that are impractical in a clinical setting and can lead to significant cost. Investigation into strategies that optimize cell production is essential. Here, we use the piezoelectric copolymer poly(vinylidene fluoride-trifluoroethylene) (PVDF-TrFE), functionalized with a poly(ethyl acrylate) (PEA) coating that drives fibronectin network formation, to enhance MSC adhesion and to present growth factors in the solid phase. Dynamic electrical cues are then incorporated, via a nanovibrational bioreactor, and the MSC response to electromechanical stimulation is investigated.

Three-Dimensional Scaffolds for Bone Tissue Engineering.

Immobilization using external or internal splints is a standard and effective procedure to treat minor skeletal fractures. In the case of major skeletal defects caused by extreme trauma, infectious diseases or tumors, the surgical implantation of a bone graft from external sources is required for a complete cure. Practical disadvantages, such as the risk of immune rejection and infection at the implant site, are high in xenografts and allografts. Currently, an autograft from the iliac crest of a patient is considered the "gold standard" method for treating large-scale skeletal defects. However, this method is not an ideal solution due to its limited availability and significant reports of morbidity in the harvest site (30%) as well as the implanted site (5-35%). Tissue-engineered bone grafts aim to create a mechanically strong, biologically viable and degradable bone graft by combining a three-dimensional porous scaffold with osteoblast or progenitor cells. The materials used for such tissue-engineered bone grafts can be broadly divided into ceramic materials (calcium phosphates) and biocompatible/bioactive synthetic polymers. This review summarizes the types of materials used to make scaffolds for cryo-preservable tissue-engineered bone grafts as well as the distinct methods adopted to create the scaffolds, including traditional scaffold fabrication methods (solvent-casting, gas-foaming, electrospinning, thermally induced phase separation) and more recent fabrication methods (fused deposition molding, stereolithography, selective laser sintering, Inkjet 3D printing, laser-assisted bioprinting and 3D bioprinting). This is followed by a short summation of the current osteochondrogenic models along with the required scaffold mechanical properties for in vivo applications. We then present a few results of the effects of freezing and thawing on the structural and mechanical integrity of PLLA scaffolds prepared by the thermally induced phase separation method and conclude this review article by summarizing the current regulatory requirements for tissue-engineered products.

IPSC-neural crest derived cells embedded in 3D printable bio-ink promote cranial bone defect repair

Cranial bone loss presents a major clinical challenge and new regenerative approaches to address craniofacial reconstruction are in great demand. Induced pluripotent stem cell (iPSC) differentiation is a powerful tool to generate mesenchymal stromal cells (MSCs). Prior research demonstrated the potential of bone marrow-derived MSCs (BM-MSCs) and iPSC-derived mesenchymal progenitor cells via the neural crest (NCC-MPCs) or mesodermal lineages (iMSCs) to be promising cell source for bone regeneration. Overexpression of human recombinant bone morphogenetic protein (BMP)6 efficiently stimulates bone formation. The study aimed to evaluate the potential of iPSC-derived cells via neural crest or mesoderm overexpressing BMP6 and embedded in 3D printable bio-ink to generate viable bone graft alternatives for cranial reconstruction. Cell viability, osteogenic potential of cells, and bio-ink (Ink-Bone or GelXa) combinations were investigated in vitro using bioluminescent imaging. The osteogenic potential of bio-ink-cell constructs were evaluated in osteogenic media or nucleofected with BMP6 using qRT-PCR and in vitro μCT. For in vivo testing, two 2 mm circular defects were created in the frontal and parietal bones of NOD/SCID mice and treated with Ink-Bone, Ink-Bone + BM-MSC-BMP6, Ink-Bone + iMSC-BMP6, Ink-Bone + iNCC-MPC-BMP6, or left untreated. For follow-up, µCT was performed at weeks 0, 4, and 8 weeks. At the time of sacrifice (week 8), histological and immunofluorescent analyses were performed. Both bio-inks supported cell survival and promoted osteogenic differentiation of iNCC-MPCs and BM-MSCs in vitro. At 4 weeks, cell viability of both BM-MSCs and iNCC-MPCs were increased in Ink-Bone compared to GelXA. The combination of Ink-Bone with iNCC-MPC-BMP6 resulted in an increased bone volume in the frontal bone compared to the other groups at 4 weeks post-surgery. At 8 weeks, both iNCC-MPC-BMP6 and iMSC-MSC-BMP6 resulted in an increased bone volume and partial bone bridging between the implant and host bone compared to the other groups. The results of this study show the potential of NCC-MPC-incorporated bio-ink to regenerate frontal cranial defects. Therefore, this bio-ink-cell combination should be further investigated for its therapeutic potential in large animal models with larger cranial defects, allowing for 3D printing of the cell-incorporated material.

Bovine-derived xenograft is a viable bone graft substitute in multilevel, instrumented, spinal fusion.

To evaluate radiological outcomes following the use of xenogeneic bone graft substitute (BGS) in patients undergoing multisegmental spinal fusion. Data exists for single level and short segment fusions, there presently is a paucity of data on fusion rate after bone augmentation with BGS in multisegmental posterior spinal fusion (PSF). The leading concern is pseudarthrosis, which often leads to a loss of correction after PSF. Therefore, the bone graft is an essential aspect of PSF. We retrospectively analysed the radiological data of a consecutive cohort of patients who had been treated for adolescent idiopathic scoliosis (AIS) via multisegmental spinal fusion, in whom a bovine derived BGS had been used and had a complete dataset of 24 months follow-up. The Cobb angle of the main curve was measured pre-operatively and then at 6, 12 and 24 months post-operatively. Loosening of the screws was recorded at the same post-operative time points. After applying inclusion and exclusion criteria, 28 patients were included. We found no significant change of the cobb angle from the main curve as well as the cobb angle from the thoracic kyphosis during the 24 months of follow up. No patient showed a lack of bony fusion. There was 1 revision surgery, which was due to trauma. In this cohort, all patients showed successful bone fusion during a 24-month follow-up. Additionally, there was no change in the Cobb angle during the 2-year post-operative period. Our data indicates that the use of bovine-derived BGS supports bone fusion after multisegmental posterior instrumented fusion of the spine.

Freeze Casting with Bioceramics for Bone Graft Substitutes

Freeze casting with bioceramics affords the opportunity to create the next generation of bone graft substitutes. Because of its versatile material fabrication process and effective methods of structural control, freeze casting helps to meet the many criteria that are required of viable bone graft substitute biomaterials. In combination with biocompatible and resorbable ceramics and ceramic composites that can offer bone growth through osteoconduction, this process helps provide a tailored pore structure while maintaining the necessary mechanical properties for bone growth. Here, the advantages of freeze casting with bioceramics for orthopedic and dental applications are summarized: in particular, these advantages include its compatibility with a large variety of bioceramics, many forms of both uniform and localized structure control, and its ability to be used in combination with other advanced manufacturing processes.

Impact of Drilling Speed in Implantology: A Review

Background: Drilling speed during osteotomy in implant site preparation is an important factor that affects heat generation, cell vitality and primary stability and consequently Osseointegration of the implant. A thorough understanding of this impact is important for taking suitable precautions for successful dental rehabilitation. Aim: The objective of this study is to review the available literature regarding the impact of drilling speed on heat generation and other related parameters that influence the success of dental implants. Material and Methods: Suitable research papers relevant for study were identified through electronic database of available dental literature in PubMed and MEDLINE for all articles published till February, 2021. Peer-reviewed dental and PubMed indexed journals were selected. Search was done using certain relevant key words and terms. Results: The initial search revealed a total of 281 articles which were then screened and a total of 61 articles were selected based on the inclusion criteria. Focus was laid on the studies related to drilling speed and its impact on osseointegration, heat generation during osteotomy, drilling speed and bone viability, drilling speed and primary stability of implant and particle size of the bone collected. Heat generation during implant placement is affected by multiple factors with drilling speed being one of them. Conclusion: Researchers have reached contradictory conclusions regarding the impact of drilling speed on heat generation during osteotomy and other parameters. However, studies in the recent past are favoring low speed drilling owing to the advantage of perfect control of the drilling depth and the possibility of collection of a considerable amount of viable granular bone grafts during the procedure.

Generation of bone grafts using cryopreserved mesenchymal stromal cells and macroporous collagen-nanohydroxyapatite cryogels.

Bone tissue engineering strategy involves the 3D scaffolds and appropriate cell types promoting the replacement of the damaged area. In this work, we aimed to develop a fast and reliable clinically relevant protocol for engineering viable bone grafts, using cryopreserved adipose tissue-derived mesenchymal stromal cells (MSCs) and composite 3D collagen-nano-hydroxyapatite (nanoHA) scaffolds. Xeno- and DMSO-free cryopreserved MSCs were perfusion-seeded into the biomimetic collagen/nanoHA scaffolds manufactured by cryotropic gelation and their osteoregenerative potential was assessed in vitro and in vivo. Cryopreserved MSCs retained the ability to homogenously repopulate the whole volume of the scaffolds during 7 days of post-thaw culture. Moreover, the scaffold provided a suitable microenvironment for induced osteogenic differentiation of cells, confirmed by alkaline phosphatase activity and mineralization. Implantation of collagen-nanoHA cryogels with cryopreserved MSCs accelerated woven bone tissue formation, maturation of bone trabeculae, and vascularization of femur defects in immunosuppressed rats compared to cell-free collagen-nanoHA scaffolds. The established combination of xeno-free cell culture and cryopreservation techniques together with an appropriate scaffold design and cell repopulation approach accelerated the generation of viable bone grafts.

A Novel Xenograft Bone Substitute Supports Stable Bone Formation in Circumferential Defects Around Dental Implants in Minipigs.

The aim of this study was to evaluate and compare bone growth and implant integration in circumferential defects with two commercially available bone substitutes (demineralized bovine bone mineral [DBBM]). Circumferential defects were created in the mandibles of minipigs (n = 10), and Bone Level Tapered implants (Straumann Roxolid with SLActive surface) were placed. The defects (4-mm-deep circumferential defect, 2 mm around each implant) were augmented with either sintered bovine bone mineral (test, cerabone) or natural bovine bone mineral (control, Bio-Oss). Bone formation and tissue composition in augmented sites were histomorphometrically assessed after 8 and 12 weeks of healing time (n = 5 each), respectively, in terms of the percentage of area of newly formed bone to total area, bone-to-implant contact (BIC), and crestal bone height relative to the implant shoulder (first bone-to-implant contact [fBIC]). Bone formation in all defect sites was adequate and equivalent for both groups at individual healing time points. The amount of residual graft material was comparable in both groups after 8 and 12 weeks, with no significant resorption in either group. The mean newly formed bone area in the test group amounted to 46.7% ± 5.1% and 48.7% ± 4.0% after 8 and 12 weeks vs 47.0% ± 4.8% and 47.8% ± 7.3% in the control group, respectively. BIC and fBIC as individually assessed for the lingual and buccal aspects were comparable at both healing time points without any statistically significant differences between the groups. A slightly greater variability of fBIC was observed within the test group. The results of this study indicate that test and control materials both represent viable bovine bone graft material that equivalently support the formation of new and stable bone volume specifically when used for simultaneous augmentation around implants.

Split Calvarial Grafting for Closure of Large Cranial Defects: The Ideal Option?

Among the various cranioplasty options for reconstruction of large post-craniectomy defects, split calvarial grafting offers numerous significant advantages such as the provision of viable autogenous bone graft material comprising of living, immunocompatible bony cells that integrate fully with the skull bone bordering the cranial defect. Its potential for revascularization and subsequent integration and consolidation allows its successful use even in previously infected or otherwise compromised recipient sites. Its excellent contour match at the recipient site and low cost as compared to various alloplastic implant materials often makes it preferable to the latter. Surgeon's skill, dexterity, expertise and experience are important factors to be considered in this highly technique-sensitive procedure.

Biological drilling: Implant site preparation in a conservative manner and obtaining autogenous bone grafts

Background/Aim: The drilling process for insertion of an implant should be as conservative as possible, as not to damage the future implant bed. If this drilling is conservative additional bone can be obtained to be used afterwards, during the same surgery, as bone graft particulate if needed. The objective of this study was to evaluate the efficiency of a biological low-speed drilling and to analyse the bone obtained in order to ascertain viability and vitality of the contained bone cells. Also, the bone obtained from the low-speed drilling was compared with bone obtained with high speed drilling and irrigation, collected through a filter in aspiration system. Material and Methods: In this pilot study, samples of biological drilling (low speed without irrigation) were collected in five patients undergoing implant surgery. In the same patients a high speed drilling with irrigation was also used. Bone of the drilling was collected through a filter in the aspiration system. Subsequently the samples were analysed by conventional histology and cultivated in order to observe cell growth. Results: The samples of bone obtained by biological drilling showed live cells in the conventional optical microscopy and cell growth after cultivation. The bone obtained with drilling at high revolutions showed no living cells and no cell growth after cultivation. Conclusions: The biological drilling at low speed offered two advantages compared to drilling at high speed with irrigation. The first of these is the perfect control of the drilling depth as the marks of the burs are visible during drilling; the second is possibility of collection of a large number of viable particulate bone grafts without increasing time and complexity of the surgery, which allows immediate augmentation of bone if needed.

Biomimetic Approaches for Bone Tissue Engineering.

Although autologous bone grafts are considered a gold standard for the treatment of bone defects, they are limited by donor site morbidities and geometric requirements. We propose that tissue engineering technology can overcome such limitations by recreating fully viable and biological bone grafts. Specifically, we will discuss the use of bone scaffolds and autologous cells with bioreactor culture systems as a tissue engineering paradigm to grow bone in vitro. We will also discuss emergent vascularization strategies to promote graft survival in vivo, as well as the role of inflammation during bone repair. Finally, we will highlight some recent advances and discuss new solutions to bone repair inspired by endochondral ossification.

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep.

Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p < 0.05). In conclusion, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017.

Binder-jetting 3D printing and alloy development of new biodegradable Fe-Mn-Ca/Mg alloys.

Bone grafting is widely used for the treatment of cranio-maxillofacial bone injuries. 3D printing of biodegradable Fe alloy is anticipated to be advantageous over current bone grafting techniques. 3D printing offers the fabrication of precise and tailored bone grafts to fit the patient specific bone defect needs. Biodegradable Fe alloy is a good candidate for 3D printing synthetic grafts to regenerate bone tissue without eliciting complications. CALPHAD theoretical models were used to develop new Fe-Mn-Ca/Mg alloys to enhance the degradation rates of traditional Fe-Mn alloys. In vitro experimental results also showed enhanced degradation rates and good cytocompatibility of sintered Fe-Mn-Ca/Mg compacts. 3D printing of Fe-Mn and Fe-Mn-1Ca alloys further demonstrated their feasibility as potentially viable bone grafts for the future.

Overview of Biologics.

Biologics in the appropriate biomechanical environment provide viable bone graft substitutes for repair of injured bone while promoting bone formation and osseointegration. Surgeons must recall the basics of bone structure, the principles of Wolff's law, and the components and steps of new bone formation to optimize the fusion environment and to maximize patient outcomes.

Assessment of activated porous granules on implant fixation and early bone formation in sheep

SummaryBackground/ObjectiveDespite recent progress in regeneration medicine, the repair of large bone defects due to trauma, inflammation and tumor surgery remains a major clinical challenge. This study was designed to produce large amounts of viable bone graft materials in a novel perfusion bioreactor to promote bone formation.MethodsCylindrical defects were created bilaterally in the distal femurs of sheep, and titanium implants were inserted. The concentric gap around the implants was randomly filled either with allograft, granules, granules with bone marrow aspirate (BMA) or bioreactor activated granule (BAG). The viable BAG consisted of autologous bone marrow stromal cells (BMSCs) seeded upon porous scaffold granules incubated in a 3D perfusion bioreactor for 2 weeks prior to surgery. 6 weeks after, the bone formation and early implant fixation were assessed by means of micro-CT, histomorphometry, and mechanical test.ResultsMicroarchitectural analysis revealed that bone volume fraction and trabecular thickness in the allograft were not statistically different than those (combination of new bone and residue of granule) in the other 3 groups. The structure of the allograft group was typically plate-like, while the other 3 groups were combination of plate and rod. Histomorphometry showed that allograft induced significantly more bone and less fibrous tissue in the concentric gap than the other 3 granule groups, while the bone ingrowth to implant porous surface was not different. No significant differences among the groups were found regarding early implant mechanical fixation.ConclusionIn conclusion, despite nice bone formation and implant fixation in all groups, bioreactor activated graft material did not convincingly induce early implant fixation similar to allograft, and neither bioreactor nor by adding BMA credited additional benefit for bone formation in this model.

An automated perfusion bioreactor for the streamlined production of engineered osteogenic grafts.

A computer-controlled perfusion bioreactor was developed for the streamlined production of engineered osteogenic grafts. This system automated the required bioprocesses, from the initial filling of the system through the phases of cell seeding and prolonged cell/tissue culture. Flow through chemo-optic micro-sensors allowed to non-invasively monitor the levels of oxygen and pH in the perfused culture medium throughout the culture period. To validate its performance, freshly isolated ovine bone marrow stromal cells were directly seeded on porous scaffold granules (hydroxyapatite/β-tricalcium-phosphate/poly-lactic acid), bypassing the phase of monolayer cell expansion in flasks. Either 10 or 20 days after culture, engineered cell-granule grafts were implanted in an ectopic mouse model to quantify new bone formation. After four weeks of implantation, histomorphometry showed more bone in bioreactor-generated grafts than cell-free granule controls, while bone formation did not show significant differences between 10 days and 20 days of incubation. The implanted granules without cells had no bone formation. This novel perfusion bioreactor has revealed the capability of activation larger viable bone graft material, even after shorter incubation time of graft material. This study has demonstrated the feasibility of engineering osteogenic grafts in an automated bioreactor system, laying the foundation for a safe, regulatory-compliant, and cost-effective manufacturing process.

A Novel Oxysterol Analogue Promotes In Vitro and In Vivo Bone Regeneration

INTRODUCTION: The repair of complex craniofacial defects poses significant reconstructive challenges. Current methods employing autologous bone grafts or alloplastic implants are fraught with complications. Tissue engineering approaches using bone morphogenetic proteins (BMPs) are associated with adverse side effects and exorbitant costs. Here we investigate a novel molecule with significant osteoinductive capacity for its potential use in clinical applications. We examine the impact of Oxy133, a novel oxysterol analogue, on In Vitro and In Vivo osteogenic differentiation of rabbit bone marrow stromal cells (BMSCs). METHODS: Rabbit BMSCs were isolated, cultured, and treated with control media and varying concentrations of Oxy133 or BMP-2. In Vitro osteogenic differentiation was assessed via alkaline phosphatase (ALP) assay, quantitative real-time PCR of osteogenic genes, and mineralization assays. In Vivo activity was measured by healing of critical-sized rabbit calvarial defects that were treated with a collagen sponge carrying an inert control vehicle, collagen sponge carrying Oxy133, collagen sponge carrying BMP-2, or left untreated. The calvarium was harvested after seven weeks for histologic and radiographic analysis. RESULTS: Rabbit BMSCs treated with Oxy133 demonstrated increased ALP activity, up-regulation of osteogenic gene expression, and increased mineralization of cultures compared to controls. Oxy133-treated cells demonstrated In Vitro osteogenic differentiation with an efficacy similar to that of cells treated with BMP-2. Critical-sized rabbit calvarial defects showed complete bone regeneration when treated with collagen sponges carrying Oxy133, with an efficacy similar to that seen in animals treated with BMP-2 (Figure 1).Figure 1: Oxy133 promotes cranial bone regeneration.CONCLUSIONS: Oxy133 induces osteogenic differentiation in rabbit BMSCs as effectively as BMP-2 in both In Vitro and In Vivo models. Oxysterols, which are relatively inert and less costly to scale for mass production, may therefore represent a viable alternative to BMP-2 in bone tissue engineering models. Its application to the design of a clinically viable, safe, and cost effective bone graft substitute warrants further study.

Biological performance of a polycaprolactone-based scaffold plus recombinant human morphogenetic protein-2 (rhBMP-2) in an ovine thoracic interbody fusion model.

We develop a sheep thoracic spine interbody fusion model to study the suitability of polycaprolactone-based scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2) as a bone graft substitute within the thoracic spine. The surgical approach is a mini-open thoracotomy with relevance to minimally invasive deformity correction surgery for adolescent idiopathic scoliosis. To date there are no studies examining the use of this biodegradable implant in combination with biologics in a sheep thoracic spine model. In the present study, six sheep underwent a 3-level (T6/7, T8/9 and T10/11) discectomy with randomly allocated implantation of a different graft substitute at each of the three levels: (a) calcium phosphate (CaP) coated polycaprolactone-based scaffold plus 0.54 μg rhBMP-2 (b) CaP-coated PCL-based scaffold alone or (c) autograft (mulched rib head). Fusion was assessed at 6 months post-surgery. Computed Tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison with either PCL-based scaffold alone or autograft. These results were supported by histological evaluations of the respective groups. Biomechanical testing revealed significantly higher stiffness for the rhBMP-2 plus PCL-based scaffold group in all loading directions in comparison with the other two groups. The results of this study demonstrate that rhBMP-2 plus PCL-based scaffold is a viable bone graft substitute, providing an optimal environment for thoracic interbody spinal fusion in a large animal model.