Bone Formation and Regeneration Via Citric Acid-Based Composites

点击翻译按钮获取中文摘要

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.