Injectable Delivery of Bone Growth Factor, HomoSer3-AIII

描述(申请人提供)：虽然骨折通常愈合成功，但相当多的人，在美国每年近30万次骨折，愈合缓慢或根本不愈合。除了这些骨折，在美国，每年大约有20万例脊柱融合术治疗下腰痛。脊柱融合消耗了所有可用的骨移植替代品的一半以上，包括来自身体的人骨。重要的是，可用于治疗骨折和融合的生长因子极其昂贵。使用从患者身上获取的骨会增加发病率，而且组织移植物和生长因子的输送都需要开放手术，这可能会增加患者的医疗并发症风险。由于当前实践的这些局限性和费用，迫切需要一种成本效益高的产品，可以直接注射到骨修复部位以加速愈合。 我们研究的目标是开发一种经济高效、方便的骨愈合产品，它由一种从血管紧张素衍生的多肽生长因子HomoSer3-AIII在可注射凝胶Oxiplex(R)中组成，该凝胶由两种生物相容的合成聚合物组成。目标是： 1)。根据操控性、生物相容性、骨愈合疗效和多肽稳定性，从三种制剂中选择一种注射系统，使用Oxiplex技术将HomoSer3-AIII经皮递送到骨损伤部位。 2)。在两种骨愈合动物模型中，确定HomoSer3-AIII在使用所选注射系统进行骨愈合方面的疗效。 这个项目成功的可能性很高，因为我们已经证明了在ALL存在的情况下培养的MSC能够表达骨细胞的特征(碱性磷酸酶)。这些数据支持这样的假设，即血管紧张素肽可以加速MSC的生长，同时保持其向骨分化的能力。我们还发现，Oxiplex/SP(一种与这里将要开发的配方类似，目前在欧洲销售的用于减少脊柱手术后硬膜外纤维化的配方)在大鼠胫骨修复模型中加速了骨的形成，并且随着HomoSer3-AIII的加入，凝胶中的骨沉积、重塑和修复显著增加。如果该项目和未来的第二阶段SBIR开发研究产生了一种用于骨愈合的成本效益配方，FzioMed将生产、营销并将该产品分销给整形外科医生。

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.