ABSORBABLE IMPLANTS AS BMP-2 CARRIERS IN BONE CHAMBERS

可吸收植入物作为骨腔中的 BMP-2 载体

• 批准号: 2131124
• 负责人: HOWARD WINET
• 金额: $ 21.88万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2131124
• 关键词: acid base balance; angiogenesis; biomaterial compatibility; bone regeneration; copolymer; cytokine; dental implants; digital imaging; fluorescence microscopy; fluorescent dye /probe; histogenesis; laboratory rabbit; physiologic bone resorption; recombinant proteins; statistics /biometry

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).

重建手术的理想植入物可促进再生 失去的组织并消失得足够快，足以进行修复手术 不必要的。开发和微调这样的材料以匹配宿主 植入的组织需要清楚地了解如何 再吸收植入物和宿主组织相互作用。 本研究将调查 骨及其微血管系统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)。 载体摩尔比为 50:50 聚丙交酯-聚乙交酯共聚物（PLGA）。 它将形成 螺纹并插入骨室窗胫骨植入物 (BCI) 通过活体显微镜可以观察骨 血管形成、微循环、血管渗漏、新骨生成和 聚合物吸收。 线程将通过吸入加载 BMP-2。 使用荧光指示剂，pH 和 BMP-2 浓度的变化将 测量以检验两个假设：(l) 降解聚合物周围的 pH 值 体内有足够的缓冲以允许骨传导； (2) BMP-2 单调增加小梁生长成急性的速率 骨缺损。 将通过静脉注射评估局部 pH 值变化 注射荧光 pH 指示剂半萘霍达氟 (SNARF- 1) 右旋糖酐 20kDa 和 rBMP-2 与罗丹明-FITC 右旋糖酐 20kDa 混合。 每周的荧光图像彩色显微照片将显示 rBMP-2 浓度以及 pH 值。血液图像将增强 FITC-葡聚糖和荧光 1.75 微米微球和骨图像 土霉素和 DCAF。 通过交替透射和外延 荧光照明和改变荧光立方体 活体显微镜，所有感兴趣的结构都将被成像并 记录用于视频数字化、测量和分析。数据将是 每周根据功率统计数据确定的样本量收集数据（14 兔子）并与历史对照和同期对照进行比较。 血流量和渗漏测量数据将用于解释 缓冲机制。 假设 l 的验证将是 取决于在没有证据的情况下合并发生的程度 异物反应以及骨骼和血管的程度 再生不受聚合物线吸收的抑制。 确认 假设 2 的结果将由骨并置的程度决定 超过了单独的聚合物，并且超过的程度 历史对照（不含聚合物或 BMP 的 BCI）。