Bone Formation and Regeneration Via Citric Acid-Based Composites

描述（由申请人提供）：美国每年约有500，000例涉及使用骨替代品的手术。据估计，这些手术每年的费用为25亿美元。尽管自体移植物提供了骨置换的最佳生物学选择，但由于供应限制和额外手术引起的供体部位发病率，其使用受到限制。同种异体移植消除了供体部位发病率和供应有限的问题，但它们具有从供体到受体的疾病传播或感染的固有风险。为了解决目前用于骨科组织工程的材料的局限性，我们开发了一种新型复合材料，由柠檬酸基弹性体和生物陶瓷组成。该复合材料具有获得广泛的机械和降解特性的潜力，并作为药物控释的储库。本提案的目的是评估聚（柠檬酸1，8辛酯）-生物陶瓷复合材料的降解和药物释放特性，并研究使用这些复合材料进行体内骨再生的可行性。羟基磷灰石（HA）将被用作模型生物陶瓷。为了实现这一目标，具体的目标是：1）合成和表征聚（1，8-柠檬酸辛酯）-羟基磷灰石（POC-HA）复合材料。具体来说，我们将a）合成和制造由POC-HA组成的可延展的“油灰样”和不可延展的复合支架，B）研究添加二醇N-甲基二乙醇胺（MDEA）对POC-HA的机械和降解特性的影响，c）评估可延展的复合材料释放活性血管内皮生长因子（VEGF）、骨形态发生蛋白-2（BMP-2）、和地塞米松，和d）表征POC-HA的体外成骨特性，和2）评估POC-HA复合材料的体内生物相容性和骨整合。具体而言，我们将a）将复合材料植入家兔股骨临界尺寸缺损中，和B）通过组织学、免疫组织化学、X射线和机械测试评价植入部位的炎症、新血管形成和新骨形成。所获得的知识将提高我们对如何设计材料的理解，这些材料将更好地与宿主骨结合或替代宿主骨。在美国，每年约有50万例涉及使用骨替代品的手术。据估计，这些手术每年的费用为25亿美元。为了解决目前用于骨科组织工程的材料的局限性，我们开发了一种新型复合材料，由柠檬酸基弹性体和生物陶瓷组成。

DESCRIPTION (provided by applicant): Approximately 500,000 procedures that involve the use of bone substitutes are performed each year in the United States. The annual cost of these procedures is estimated to be 2.5 billion dollars. Although autografts provide the best biological option for bone replacement, their use is limited due to supply limitations and donor-site morbidity caused by the additional surgery. Allografts eliminate the issue of donor-site morbidity and limited supply but they have an inherent risk of disease transmission or infection from donor to recipient. To address the limitations of materials currently used in orthopaedic tissue engineering, we have developed a novel composite material that consists of a citric acid-based elastomer and a bioceramic. The composite has the potential to acquire a wide range of mechanical and degradation characteristics and serve as a depot for controlled drug release. The goal of this proposal is to assess the degradation and drug release characteristics of poly(1,8 octanediol citrate)-bioceramic composites and investigate the feasibility of using these composites for in vivo bone regeneration. Hydroxyapatite (HA) will be used as a model bioceramic. Towards this goal, the specific aims are to: 1) synthesize and characterize poly(1,8 octanediol citrate)-hydroxyapatite (POC-HA) composites. Specifically, we will a) synthesize and fabricate malleable "putty-like" and non-malleable composite scaffolds consisting of POC-HA, b) investigate the effects of adding the diol N-methyldiethanolamine (MDEA) on the mechanical and degradation characteristics of POC-HA, c) assess the ability of the malleable composites to release active vascular endothelial growth factor (VEGF), bone morphogenic protein-2 (BMP-2), and dexamethasone in a controlled manner, and d) characterize the in vitro osteogenic properties of POC-HA, and 2) assess the biocompatibility and osteointegration of POC-HA composites in vivo. Specifically, we will a) implant the composites into a femoral critical size defect in rabbit, and b) evaluate the implant site for inflammation, neovascularization, and new bone formation via histology, immunohistochemistry, x-ray, and mechanical testing. The knowledge obtained will improve our understanding of how to engineer materials that will better integrate with or replace host bone. Approximately 500,000 procedures that involve the use of bone substitutes are performed each year in the United States. The annual cost of these procedures is estimated to be 2.5 billion dollars. To address the limitations of materials currently used in orthopaedic tissue engineering, we have developed a novel composite material that consists of a citric acid-based elastomer and a bioceramic.