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Novel Bone Graft Material With Osteoinductive and Hemostatic Function

具有骨诱导止血功能的新型骨移植材料

基本信息

批准号：
7746739
负责人：
BO HAN
金额：
$ 9.98万
依托单位：
CEREMED, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7746739
关键词：
Adverse effects Alkaline Phosphatase Allografting Animal Testing Animals Autologous Transplantation Benchmarking Biocompatible Biological Biological Assay Blood Blood Clot Blood coagulation Blood flow Bone Growth Bone Matrix Bone Regeneration Bone Tissue Bone Transplantation Calcium Cephalic Characteristics Clinical effectiveness Defect Dental Dental Implants Development Drug Formulations Effectiveness Ensure Equilibrium Evaluation Excision Future Glycerol Goals Growth Factor Harvest Healed Hemorrhage Hemostatic Agents Hemostatic function Human In Vitro Infection Inflammatory Intramuscular Kinetics Marketing Measures Mechanics Methods Modeling Natural regeneration Operative Surgical Procedures Organ Transplantation Orthopedic Procedures Oryctolagus cuniculus Osteogenesis Oxides Patients Phase Polymers Postoperative Period Procedures Property Rattus Recovery Research Research Personnel Risk Sheep Site Spinal Fusion Staging Stearates Sterilization for infection control Surface Technology Testing Tissues Transplanted tissue Trauma Validation Variant Water Waxes age related aqueous base biomaterial compatibility bone bone wax copolymer cost early onset healing high risk implant material implantation improved in vivo novel particle pre-clinical pre-clinical research prevent public health relevance reconstruction repaired scaffold tumor

项目摘要

DESCRIPTION (provided by applicant): Bone is one of the most implanted materials in the body, second only to blood. The market for bone grafting and dental implants is currently over $4.8 billion and is expected to grow rapidly in the future. Autograft has traditionally been used, but limited supply, donor-site risks, and cost created a demand for bone graft substitutes. As an osteoinductive bone graft material, demineralized bone matrix (DBM) has emerged as an effective alternative to autograft. But without a carrier, DBM is difficult to handle and its particles may be dispersed by blood from the bone defect, which weakens its clinical effectiveness. A malleable, hemostatic, and rapidly resorbable carrier may significantly improve DBM's handling and clinical effectiveness. Alkylene oxide copolymer (Ostene) invented by USC researchers has all these characteristics. It was recently cleared by the FDA as a synthetic alternative to bone wax; it sticks well to wet surfaces and stops bone bleeding by mechanical occlusion. Ostene is a combination of biocompatible water-soluble polymers which dissolves completely within 2-3 days of implantation. It is non-aqueous and non-inflammatory; it does not increase the risk of infection or inhibit osteogenesis. This combination of properties makes Ostene an ideal carrier for delivery of DBM to any bone defect. The objective of this project is to develop a novel DBM-Ostene bone graft that is both osteoinductive and hemostatic, osteoconductive and easy to handle. The polymer's non-aqueous composition would act as a natural preservative for DBM, activating it only after implantation. The carrier would prevent blood flow from the bone defect and create a more concentrated DBM scaffold for osteoinductivity and better bone fusion; rapid resorption would allow quick activation of DBM and earlier onset of healing without adding risk. This application describes the research leading to new compound's pre-clinical formulation, in vitro validation, stability, osteoinductivity testing, and kinetics of release study, as well as in vivo functional evaluation and biocompatibility studies. The research will be followed by higher order animal studies in phase II to test the optimal composite for specific functional applications, such as spinal fusion and sternal bone repair. Successful development of the final DBM product will shorten the current bone graft procedure, improve the bone graft's handling, promote stronger bone fusion, and enable earlier healing and post-operative recovery without adding risk. PUBLIC HEALTH RELEVANCE: Bone tissue, used to fill defects caused by trauma, tumor resection, reconstruction, and repair of congenital or age-related problems, is one of the most implanted materials in the body, second only to blood. Autograft - patient's own bone -- has been the bone graft of choice, but its limited supply and multiple procedures required for harvesting and implantation combined with risk and high cost created a growing demand for functional bone graft substitutes; several alternatives have become available, but the materials have problems ranging from insufficient osteinductivity and difficult handling to lack of bone hemostasis and side effects. We propose to combine Demineralized Bone Matrix (DBM) - a human bone-derived allograft most closely resembling the patient's own tissue - with a newly available inert, malleable, and rapidly resorbable bone hemostasis material as a carrier to create an easy to handle, highly osteoinductive, and versatile bone graft substitute with added hemostatic function which will help shorten the current orthopedic procedure, strengthen bone fusion, and promote significantly earlier onset of healing and postoperative recovery without increased risk.

描述（由申请人提供）：骨是人体内植入最多的材料之一，仅次于血液。骨移植和牙科植入物市场目前超过48亿美元，预计未来将迅速增长。传统上使用自体移植，但有限的供应，供体部位的风险和成本创造了对骨移植替代品的需求。脱矿骨基质（DBM）作为一种骨诱导性骨移植材料，已成为自体骨移植的有效替代品。但由于没有载体，DBM难以处理，其颗粒可能会被骨缺损处的血液分散，这削弱了其临床效果。具有延展性、止血性和快速吸收性的载体可显著改善DBM的操作和临床有效性。USC研究人员发明的环氧烷共聚物（Ostene）具有所有这些特性。它最近被FDA批准为骨蜡的合成替代品;它能很好地粘附在潮湿的表面上，并通过机械咬合来阻止骨出血。Ostene是生物相容性水溶性聚合物的组合，在植入后2-3天内完全溶解。它是非水性且非炎症性的;它不会增加感染的风险或抑制成骨。这种特性的组合使Ostene成为将DBM输送到任何骨缺损的理想载体。本项目的目的是开发一种新型DBM-Ostene骨移植物，该骨移植物具有骨诱导性和止血性，骨传导性和易于操作。这种聚合物的非水性成分将作为DBM的天然防腐剂，只有在植入后才能激活它。该载体将防止血液从骨缺损流出，并产生更浓缩的DBM支架，用于骨诱导性和更好的骨融合;快速吸收将允许DBM的快速活化和更早的愈合，而不会增加风险。本申请描述了导致新化合物的临床前制剂、体外验证、稳定性、骨诱导性测试和释放动力学研究以及体内功能评价和生物相容性研究的研究。该研究将在第二阶段进行更高级的动物研究，以测试特定功能应用的最佳复合材料，如脊柱融合和胸骨修复。最终DBM产品的成功开发将缩短目前的植骨手术，改善植骨的处理，促进更强的骨融合，并实现更早的愈合和术后恢复，而不会增加风险。公共卫生相关性：骨组织，用于填补创伤、肿瘤切除、重建以及先天性或年龄相关问题的修复造成的缺损，是人体内植入最多的材料之一，仅次于血液。自体移植物-患者自身的骨-一直是骨移植物的选择，但其有限的供应和采集和植入所需的多个程序与风险和高成本相结合，创造了对功能性骨移植替代品的日益增长的需求;已经有几种替代品可用，但材料存在问题，从骨诱导性不足和难以处理到缺乏骨止血和副作用。我们建议将联合收割机脱矿骨基质（DBM）--一种与患者自身组织最相似的人骨源性同种异体移植物--与一种新的惰性、可延展和可快速吸收的骨止血材料结合作为载体，以创造一种易于操作、高度骨诱导和多功能的骨移植替代物，并增加止血功能，这将有助于缩短当前的骨科手术，加强骨融合，并显著促进愈合和术后恢复的早期开始，而不增加风险。