INFORCING RESORBABLE BUFFERED INTERNAL FIXATION DEVICES

与使用可吸收骨科固定装置相关的炎症反应可以通过在聚乳酸-乙醇酸(“PGLA”)固定装置中加入长效缓冲液来消除，该固定装置将中和酸性降解产物。骨传导磷酸钙，羟基磷灰石(HA)，作为缓冲剂，有效地减缓了固定物降解时的pH下降速度。HA可促进骨向内生长，避免固定物松动，并起到缓冲作用。本项目的目标是通过使用自增强纤维来稳定该固定器的机械特性。夹具的自增强概念意味着由化学结构类似于夹具的聚合物PGLA成分或夹具的缓冲磷酸钙成分的增强纤维组成的复合材料的形成。第二阶段的实验设计将专注于两个功能增强夹具的体内临床前开发，基于获得FDA 5l0k批准的“实质等效性”要求。将描述小型(兔子)和大型(绵羊)动物模型的结构性能。小动物模型将用于筛选两个选定的候选纤维，而大动物模型将用于测试最终的夹具配置。兔实验的主要目标将是建立截骨愈合与固定装置退化相关的时间历史。最终的固定装置将用于绵羊模型，目的是展示与商业上可获得的固定装置相当的功能。建议的商业应用：在美国每年超过110万的骨折中，超过47万需要内固定设备来在愈合过程中固定骨折。虽然临床上对可吸收装置有很大的需求，但由于降解引起的炎症反应，现有的产品尚未被广泛采用。我们的研究表明，缓冲的可吸收固定装置可能会改善这些反应。开发必要的强度将满足临床对可接受的可吸收骨科材料的需求。

The inflammatory response associated with the use of resorbable orthopedic fixation devices can be eliminated by incorporating a long acting buffer into a poly(lactic-co-glycolic acid), "PGLA", fixation device which will neutralize acidic degradation products. The inclusion of the osteoconductive calcium phosphate, hydroxyapatite (HA), as a buffer in a PLOA-based fixture effectively moderates the rate of pH decline as the fixture degrades. HA promotes bony ingrowth, obviates loosening of the fixture, and acts as a buffer. It is the objective of this project to stabilize the mechanical characteristics of this fixture via the use of self-reinforcing fibers. The concept of self- reinforcement of the fixture implies the formation of a composite material comprised of reinforcing fibers of a composition similar in chemical structure to either the polymeric PGLA component of the fixture or the buffering calcium phosphate component of the fixture. The Phase II experimental design will focus on preclinical in vivo development of two functional reinforced fixture candidates, based on the requirement of "substantial equivalence" to obtain FDA 5l0k approval. Structural performance in both small (rabbit) and large (sheep) animal models will be characterized. The small animal model will be used to screen two selected fiber candidates, whereas the large animal model will be used to test the final fixture configuration. The main goal of the rabbit experiments will be to develop the temporal history of the osteotomy healing in relation to fixture degradation. The final fixture will be employed in the sheep model with the objective of demonstrating functionality equivalent to commercially available fixation devices. PROPOSED COMMERCIAL APPLICATIONS: Of the more than 1.1 million fractures in the U.S. each year, greater than 470,000 require internal fixation devices to stabilize the fracture during the healing process. While there is significant clinical demand for resorbable devices, available products have not been widely adopted because of inflammatory responses to degradation. Our studies show that a buffered resorbable fixation device may ameliorate these responses. Development of the necessary strength will address the clinical demand for acceptable resorbable orthopedic materials.