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: 2131125
• 负责人: HOWARD WINET
• 金额: $ 20.45万
• 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/2131125
• 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).

理想的重建手术植入物可促进新生血管再生 组织丢失，消失得足够快，足以进行翻修手术 不必要。开发和微调这样的材料以匹配主机 它被植入的组织需要清楚地了解如何 吸收种植体与宿主组织相互作用。这项研究将调查 骨及其微血管对骨吸收聚合物的反应 过程就展开了。它还将调查对这种互动的影响 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)。载体的摩尔比为50：50 共聚聚乳酸-聚乙交酯(PLGA)。它将形成一个 植入骨腔窗胫骨种植体(BCI) 活体显微镜可以通过它来观察骨骼 血管化，微循环，血管渗漏，新骨生成和 聚合物再吸收。线程将通过吸入的方式加载BMP-2。 使用荧光指示剂，pH和BMP-2浓度将发生变化 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；以及(2)BMP-2 单调增加骨小梁生长成为急性 骨缺损症。局部酸碱值的变化将通过静脉注射进行评估 注射荧光pH指示剂Semphthorhodafluor(snarf- 1)葡聚糖20 kDa和rBMP-2与罗丹明-FITC葡聚糖20 kDa混合。 每周荧光图像的彩色显微照片将显示 RBMP-2浓度和pH。血液图像将通过 FITC-葡聚糖和荧光1.75微米微球和骨显像 用土霉素和DCAF。通过交替传输和EPI 荧光照明和变化的荧光立方体在 活体显微镜，所有感兴趣的结构都将被成像并 录制用于视频数字化、测量和分析。数据将是 每周从电力统计确定的样本大小中收集(14 兔)，并与历史对照和同期对照进行比较。 来自血流和渗漏测量的数据将被用来解释 缓冲机制。假设得到证实，L将被 由公司成立的程度决定，而没有证据表明 异物反应和骨骼和血管的程度 再生不受聚合物丝线再吸收的抑制。确认 假设2将由骨骼对位的程度决定 超过单独的聚合物，以及它超过的程度 历史对照(不含聚合物或BMP的BCI)。