INFORCING RESORBABLE BUFFERED INTERNAL FIXATION DEVICES

通过将长效缓冲液加入到聚（乳酸-共-乙醇酸）（“PGLA”）固定器械中，可以消除与使用可吸收骨科固定器械相关的炎症反应，该缓冲液将中和酸性降解产物。在基于PLOA的固定装置中加入骨传导性磷酸钙、羟基磷灰石（HA）作为缓冲剂，可有效减缓固定装置降解时的pH下降速率。HA促进骨长入，避免固定装置松动，并起到缓冲作用。本项目的目的是通过使用自增强纤维来稳定该夹具的机械特性。固定装置的自增强的概念意味着形成复合材料，该复合材料由化学结构与固定装置的聚合物PGLA组分或固定装置的缓冲磷酸钙组分相似的组成的增强纤维组成。II期实验设计将重点关注两种功能性增强固定装置候选产品的临床前体内开发，基于获得FDA 510 k批准的“实质等同性”要求。将表征小型（家兔）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种选定的候选纤维，而大动物模型将用于测试最终夹具配置。家兔实验的主要目标是开发与固定装置退化相关的截骨愈合的时间历史。最终固定装置将用于绵羊模型，目的是证明其功能等同于市售固定器械。拟议的商业应用：在美国每年超过110万例骨折中，超过470，000例需要内固定器械在愈合过程中稳定骨折。虽然对可吸收装置有很大的临床需求，但由于降解引起的炎症反应，现有产品尚未被广泛采用。我们的研究表明，缓冲可吸收固定器械可以改善这些反应。开发必要的强度将满足可接受的可吸收骨科材料的临床需求。

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.