ABSORBABLE IMPLANTS AS BMP-2 CARRIERS IN BONE CHAMBERS

重建手术的理想植入物可以促进 组织丢失并迅速消失，足以进行翻修手术 不必要。开发和微调这样的材料，以配合主机 植入的组织需要清楚地了解 吸收植入物和宿主组织相互作用。 本研究将调查 骨及其微血管对再吸收聚合物的反应， 过程展开。 它还将调查对这种相互作用的影响 使用聚合物作为细胞因子重组骨的载体 形态发生蛋白-2（rBMP-2）。 载体将为50：50摩尔比 聚乳酸-聚乙醇酸共聚物（PLGA）。 它将形成为 螺纹并插入骨腔窗口胫骨植入物（BCI） 通过活体显微镜可以观察骨骼 血管形成、微循环、血管渗漏、新骨生成和 聚合物再吸收 螺纹将通过吸收加载BMP-2。 使用荧光指示剂，pH和BMP-2浓度的变化将被 测量以测试两个假设：（1）降解聚合物周围的pH， 体内被充分缓冲以允许骨传导;和（2）BMP-2 单调地增加小梁生长成急性 骨缺损 局部pH值变化将使用静脉内 注射荧光pH指示剂萘酚或（SNARF- 1)葡聚糖20 kDa和与罗丹明-FITC葡聚糖20 kDa混合的rBMP-2。 荧光图像的每周彩色显微照片将显示 rBMP-2浓度以及pH值。血液图像将用 FITC-葡聚糖和荧光1.75微米微球和骨图像 土霉素和DCAF 通过交替传输和肾上腺素 荧光照明和改变荧光立方体上的 在活体显微镜下，将对所有感兴趣的结构进行成像， 用于视频数字化、测量和分析。数据将 每周从由功率统计确定的样本量中收集（14 兔），并与历史以及同期对照进行比较。 血流和泄漏测量的数据将用于解释 缓冲机制。 假设l的证实将是 在没有证据的情况下， 异物反应以及骨骼和血管 再生不受聚合物线再吸收的抑制。 确认 假设2的结果将取决于骨沉积的程度 超过单独聚合物的，并且超过的程度 历史对照（无聚合物或BMP的BCI）。

The ideal implant for reconstructive surgery encourages regeneration of lost tissue and disappears quickly enough to render revision surgery unnecessary.Developing and fine- tuning such a material to match the host tissue into which it is implanted requires a clear understanding of how resorbing implant and host tissue interact. This study will investigate the responses of bone and its microvasculature to resorbing polymer as the process unfolds. It will also investigate the effect on this interaction of using the polymer as a vehicle for a cytokine, recombinant bone morphogenetic protein-2 (rBMP-2). The carrier will be 50:50 molar ratio copolymer polylactide-polyglycolide (PLGA). It will be formed into threads and inserted into bone chamber window tibial implants (BCIs) through which intravital microscopy will allow observation of bone vascularization, microcirculation, vessel leakage, neo-osteogenesis and polymer resorption. Threads will be loaded with BMP-2 by imbibition. Using fluorescent indicators, pH and BMP-2 concentration changes will be measured to test two hypotheses: (l) The pH around degrading polymer in vivo is sufficiently buffered to allow osteo conduction; and (2) BMP-2 monotonically increases the rate at which trabeculae grow into an acute bone defect. Local pH changes will be assessed using intravenous injections of the fluorescent pH indicators seminaphthorhodafluor (SNARF- 1) dextran 20kDa and rBMP-2 mixed with rhodamine-FITC dextran 20kDa. Weekly color photomicrographs of fluorescent images will show changes in rBMP-2 concentration as well as pH. Blood images will be enhanced with FITC-dextran and fluorescent 1.75 micrometer microspheres and bone images with oxytetracycline and DCAF. By alternating transmitted and epi fluorescence illumination and changing fluorescence cubes on the intravital microscope, all structures of interest will be imaged and recorded for video digitization, measurement and analysis. Data will be gathered weekly from sample sizes determined by power statistics (14 rabbits) and compared with historical as well as concurrent controls. Data from blood flow and leakage measurements will be used to interpret the mechanism of buffering. Confirmation of hypothesis l will be determined by the degree to which incorporation occurs without evidence of a foreign-body reaction and by the degree to which bone and blood vessel regeneration is not inhibited by polymer thread resorption. Confirmation of hypothesis 2 will be determined by the degree to which bone apposition exceeds that for the polymer alone and the degree to which it exceeds historical controls (BCIs without polymer or BMP).