OSTEOCONDUCTIVE SCAFFOLD FOR CORTICAL BONE ALLOGRAFTS

先前的研究表明，通过部分脱钙和激光穿孔对同种异体皮质骨移植进行修饰可以增强其与宿主骨的结合。然而，这些研究也表明，合并通常发生在骨吸收之前，骨吸收可能导致过早的机械破坏。这项建议的目的是研究是否可以通过在这些脱矿和穿孔的移植物上涂上一种以富马酸聚丙烯(PPF)为基础的可生物吸收的聚合物泡沫来加速它们的结合，目的是促进骨向多孔泡沫涂层中生长。初步结果表明，PPF-泡沫涂层的皮质骨可以保持长期的强度，支架的孔洞支持骨内长。这项拨款申请将研究(L)不同孔隙率支架的制备，(2)这些支架对聚合物修饰的部分脱矿和穿孔同种异体皮质移植物力学性能的影响，以及(3)支架涂层同种异体皮质移植物在大鼠原位胫骨移植模型中的初步评估。这些研究的最终目的是确定聚合物涂层的孔隙率和厚度的最佳组合，以便能够制造脱矿和穿孔的同种异体皮质移植物，这些移植物在整个结合过程中保持足够的机械性能来抵抗正常的骨骼力量。建议的商业应用：虽然大量同种异体皮质骨移植的总体成功率约为75%-85%，这意味着无需拐杖或支架即可重返工作岗位并从事相对正常的活动，但只有50%的患者术后过程完全不复杂。约四分之一的患者需要再次手术，如自体移植或因应力性骨折延迟愈合而进行再手术。一些患者因为感染、再植、长期支撑或在某些情况下截肢而需要切除移植物。如果像提议的那样成功，我们系统的临床结果将在商业上取得独特的成功。

Previous studies have shown that modification of cortical bone allografts by partial demineralization and laser-perforation may enhance their incorporation into host bone. However, these studies also showed that incorporation is commonly preceded by bone resorption which could result in premature mechanical failure. The purpose of this proposal is to investigate whether incorporation of these demineralized and perforated allografts can be accelerated by coating them with a bioresorbable polymer foam based on polypropylene fumarate (PPF) with the objective of promoting bony ingrowth into the porous foam coating. Pilot results suggest that PPF-foam coating of cortical bone can maintain strength over time and that the porosity of the scaffold supported bony ingrowth. This grant application will investigate (l) the preparation of scaffolds varying in porosity, (2) the effect of these scaffolds on the mechanical properties of polymer modified partially demineralized and perforated cortical allografts, and (3) the initial evaluation of scaffold coated cortical allografts in an orthotopic rat tibial transplantation model. The ultimate objective of these studies is to determine an optimum combination of porosity and thickness of the polymer coating so as to enable the manufacture of demineralized and perforated cortical allografts which retain sufficient mechanical properties to resist normal skeletal forces throughout the incorporation process. PROPOSED COMMERCIAL APPLICATIONS: Although the overall success rate for massive cortical bone allografts, implying return to work and engagement in relatively normal activities without crutches or braces, is approximately 75-85%, only 50% of these patients have an entirely uncomplicated postoperative course. About a quarter of the total group require reoperations such as autologous grafting or replating for stress fractures delayed unions. Some patients require excision of the graft because of infection, reimplantation, long-term bracing or in some cases amputation. If as successful as proposed, the clinical outcomes of our system will be uniquely successful commercially.