Bone Formation and Regeneration Via Citric Acid-Based Composites

描述(由申请人提供)：在美国，每年大约进行500,000例涉及骨替代物使用的手术。这些手术每年的费用估计为25亿美元。尽管自体骨移植为骨替代提供了最佳的生物选择，但由于附加手术造成的供骨供应限制和供区并发症，其应用受到限制。同种异体移植消除了供体部位发病率和供应有限的问题，但存在从供体向受者传播疾病或感染的固有风险。为了解决目前在骨科组织工程中使用的材料的局限性，我们开发了一种新型的复合材料，它由柠檬酸基弹性体和生物陶瓷组成。该复合材料有可能获得广泛的机械和降解特性，并作为受控药物释放的仓库。本研究的目的是评估聚(1，8-辛基)柠檬酸二醇-生物陶瓷复合材料的降解和药物释放特性，并探讨将其用于体内骨再生的可行性。羟基磷灰石(HA)将作为生物陶瓷的模型材料。为此，本论文的具体目标是：1)合成和表征聚(1，8-辛基柠檬酸)-羟基磷灰石(POC-HA)复合材料。具体地说，我们将a)合成并制备由POC-HA组成的可延展性“油灰样”和非延展性复合支架，b)研究添加二醇N-甲基二乙醇胺(MDEA)对POC-HA力学和降解特性的影响，c)评估可延展性复合材料以受控方式释放活性血管内皮生长因子(VEGF)、骨形态发生蛋白-2(BMP-2)和地塞米松的能力，以及d)表征POC-HA的体外成骨性能，以及2)评估POC-HA复合材料的生物相容性和体内骨整合。具体地说，我们将a)将复合材料植入兔股骨临界大小的缺损处，以及b)通过组织学、免疫组织化学、X射线和力学测试来评估植入部位的炎症、新生血管和新骨形成。所获得的知识将提高我们对如何设计能够更好地与宿主骨结合或替换宿主骨的材料的理解。在美国，每年大约有500,000例涉及使用骨替代物的手术。这些手术每年的费用估计为25亿美元。为了解决目前在骨科组织工程中使用的材料的局限性，我们开发了一种新型的复合材料，它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.