Injectable Delivery of Bone Growth Factor, HomoSer3-AIII

骨生长因子 HomoSer3-AIII 的注射递送

• 批准号: 6992200
• 负责人: RICHARD A BERG
• 金额: $ 10万
• 依托单位: FZIOMED, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-22 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6992200
• 关键词: biomaterial development /preparation; biotechnology; gel; growth factor; injection /infusion; laboratory rat; musculoskeletal disorder therapy; musculoskeletal injury; musculoskeletal regeneration; nonhuman therapy evaluation; therapy design /development

DESCRIPTION (provided by applicant): While bone fractures usually heal successfully, a significant number, approaching 300,000 fractures per year in the US, heal slowly or do not heal at all. In addition to these fractures, in the US each year there are approximately 200,000 spinal fusions for lower back pain. Spinal fusions consume over half of all available bone graft substitutes including human bone derived from cadavers. Importantly, the available growth factors used to treat fractures and fusions are extremely expensive. Using harvested bone from the patient is associated with increased morbidity, and the delivery of both tissue grafts and growth factors require open surgery, which can increase risks of medical complications to the patient. Because of these limitations and expense of current practice, there is a tremendous need for a cost-effective product that can be injected directly into bone repair sites to accelerate healing. The goal of our study is to develop a cost-effective, convenient product for healing bone that consists of a peptide growth factor, HomoSer3-AIII, derived from angiotensin, in an injectable gel, Oxiplex(r), that consists of two biocompatible synthetic polymers. The aims are: 1). to select from three formulations, based upon handling, biocompatibility, efficacy on bone healing, and peptide stability an injectable system for the percutaneous delivery of HomoSer3-AIII to the site of bone injury using Oxiplex technology. 2). to determine the efficacy of HomoSer3-AIII on bone healing delivered using the selected injectable system in two animal models for bone healing. The probability of this project being successful is high because we have already shown that MSC grown in culture in the presence of All are capable of expressing characteristics of bone cells (alkaline phosphatase). These data support the hypothesis that angiotensin peptides can accelerate the growth of MSC while maintaining their ability to differentiate into bone. We also have shown that Oxiplex/SP, (a formulation similar to the one to be developed here and currently marketed for reduction of peridural fibrosis after spinal surgery in Europe), accelerated the formation of bone in a rat tibia repair model, and with the addition of HomoSer3-AIII to the gel, there was substantial increased bone deposition, remodeling and repair. If this project and future phase II SBIR development studies leads to a cost-effective formulation for bone healing, FzioMed will manufacture, market and distribute this product to orthopedic surgeons.

描述（由申请人提供）：虽然骨折通常会成功愈合，但在美国，每年有大量骨折（接近300，000例）愈合缓慢或根本不愈合。除了这些骨折，在美国每年大约有200，000例脊柱融合术用于下背痛。脊柱融合消耗了所有可用骨移植替代品的一半以上，包括来自尸体的人骨。重要的是，用于治疗骨折和融合的生长因子非常昂贵。使用从患者采集的骨与发病率增加相关，并且组织移植物和生长因子的递送都需要开放手术，这可能增加患者的医疗并发症的风险。由于目前实践的这些限制和费用，非常需要一种可以直接注射到骨修复部位以加速愈合的具有成本效益的产品。 我们研究的目标是开发一种具有成本效益的、方便的用于愈合骨的产品，该产品由肽生长因子HomoSer 3-AIII组成，肽生长因子HomoSer 3-AIII来源于血管紧张素，在可注射凝胶Oxiplex（r）中，Oxiplex（r）由两种生物相容性合成聚合物组成。其目标是： 1）。根据处理、生物相容性、骨愈合功效和肽稳定性，从三种制剂中选择一种注射系统，用于使用Oxiplex技术将HomoSer 3-AIII经皮递送至骨损伤部位。 2）。在两种用于骨愈合的动物模型中确定使用所选可注射系统递送的HomoSer 3-AIII对骨愈合的功效。 该项目成功的可能性很高，因为我们已经证明，在All存在下培养的MSC能够表达骨细胞的特征（碱性磷酸酶）。这些数据支持血管紧张素肽可以加速MSC生长同时保持其分化成骨的能力的假设。我们还表明，Oxiplex/SP（一种类似于此处开发的制剂，目前已在欧洲上市，用于减少脊柱手术后的硬膜外纤维化）加速了大鼠胫骨修复模型中的骨形成，并且在凝胶中加入HomoSer 3-AIII后，骨沉积、重塑和修复显著增加。如果该项目和未来的第二阶段SBIR开发研究导致骨愈合的成本效益配方，FzioMed将生产，销售和分销该产品给骨科医生。