Winet H, Bao J Y
J. Vernon Luck Sr. Orthopaedic Research Center of the Orthopaedic Hospital, Los Angeles, CA 90007, USA.
Wound Repair Regen. 1997 Oct-Dec;5(4):355-63. doi: 10.1046/j.1460-9568.1997.50410.x.
The effects of recombinant human fibroblast growth factor-2 in the presence of eroding 50:50 poly(DL-lactide-co-glycolide) on angiogenesis during acute bone defect healing were studied in the optical bone chamber. Bone chambers were loaded with disks of poly(DL-lactide-co-glycolide) surrounded by one of four doses of recombinant human fibroblast growth factor-2. Fifty-two female rabbit right tibias were implanted. Commencing with the third postimplantation week, healing into the bone chamber compartment was observed weekly, with use of intravital microscopy, until week 8. The treatment groups were as follows: unloaded, loaded with polymer only, and loaded with polymer plus-0.5, -1.0, and -10 microg recombinant human fibroblast growth factor-2. Videotaped and photographed bone images were measured and analyzed with a frame-grabber digitizing system. Comparison with controls or polymer alone revealed that angiogenesis rates were significantly above normal in rabbits loaded with polymer plus either of the two highest recombinant human fibroblast growth factor-2 doses. The effects of these doses were not, however, significantly different from each other, indicating a plateauing rather than monotonically increasing response. It was concluded that recombinant human fibroblast growth factor-2 in the dose- range studied can effectively overcome the retarding effects of eroding polymer on angiogenesis in bone, which has been reported previously by this laboratory. In contrast to these results, no statistically significant differences in angiogenesis rate as a function of time could be detected. It is suggested that this apparent lack of variation is linked to observed alterations in vessel patterns from week-to-week. The clinical relevance of these results is that inhibitory carrier effects can be compensated for by increasing the dose of loaded agent where the effect being inhibited is the one being treated, or by adding an agent specific for the inhibited effect. In either case, geometry of the carrier must be considered when programming for delivery rate.
在光学骨腔中研究了重组人成纤维细胞生长因子-2在50:50聚（DL-丙交酯-共-乙交酯）降解情况下对急性骨缺损愈合过程中血管生成的影响。将骨腔植入含有聚（DL-丙交酯-共-乙交酯）圆盘的材料，圆盘周围分别放置四种剂量之一的重组人成纤维细胞生长因子-2。对52只雌性兔的右胫骨进行植入。从植入后的第三周开始，每周使用活体显微镜观察骨腔隔室的愈合情况，直至第8周。治疗组如下：未加载组、仅加载聚合物组、加载聚合物加0.5、1.0和10微克重组人成纤维细胞生长因子-2组。用图像采集数字化系统对录像和拍摄的骨图像进行测量和分析。与对照组或仅聚合物组相比，加载聚合物加两种最高剂量重组人成纤维细胞生长因子-2之一的兔的血管生成率显著高于正常水平。然而，这两种剂量的效果彼此之间没有显著差异，表明存在平台效应而非单调增加的反应。得出的结论是，在所研究的剂量范围内，重组人成纤维细胞生长因子-2可以有效克服降解聚合物对骨血管生成的抑制作用，本实验室之前已有相关报道。与这些结果相反，未检测到血管生成率随时间变化的统计学显著差异。有人认为，这种明显缺乏变化与每周观察到的血管模式改变有关。这些结果的临床意义在于，当被抑制的效应是正在治疗的效应时，可以通过增加加载剂的剂量或添加针对被抑制效应的试剂来补偿抑制性载体效应。在任何一种情况下，在规划给药速率时都必须考虑载体的几何形状。
