Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects
Quantitative assessment of scaffold and growth factor-mediated repair of critically sized bone defects
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DOI：
10.1002/jor.20372
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发表时间：
2007-07-01
影响因子：
2.8
通讯作者：
Guldberg, Robert E.
中科院分区：
文献类型：
--
作者：
Oest, Megan E.;Dupont, Kenneth M.;Guldberg, Robert E.
采用8 mm大鼠节段性骨缺损模型，定量评价含或不含生长因子的纵向取向L-丙交酯-共D，L-丙交酯支架材料促进骨愈合的能力。骨形态发生蛋白-2和转化生长因子-β3，结合RGD-海藻酸盐水凝胶，在先前显示协同诱导异位矿化的剂量下，被共同输送到聚合物支架内的股骨缺损处。采用一种新型的模块化复合种植体设计，实现了可重复稳定的固定，为体内三维骨长入的纵向显微CT监测提供了窗口，并允许进行功能整合的扭转生物力学测试。连续的Micro-CT分析显示，无论有无生长因子，支架处理的缺损区在4~16周内骨内长显著增加，而空白缺损组的骨长入没有随时间增加。与未治疗相比，单独使用支架治疗可改善16周时的缺损区稳定性，但不能实现骨愈合或机械功能的恢复。骨形态发生蛋白-2和转化生长因子-β3增强支架在4周和16周均显著增加骨形成，但在6例中只有2例在缺损区产生骨桥接。组织学评估表明，骨首先在支架的外围形成，随后支架内部的矿物质沉积较为有限，表明参与初始愈合反应的细胞主要来自骨膜。这项研究介绍了一个具有挑战性的节段性骨缺损模型，该模型有助于定量评估修复临界大小的骨缺损的策略。通过植入含有生长因子的结构聚合物支架，促进了缺损区的愈合。然而，这些结构的功能整合似乎受到缓慢降解支架的持续存在和次佳剂量或骨诱导信号传递的限制。(C)2007年整形外科研究会。由威利期刊出版公司出版。
An 8-mm rat segmental defect model was used to evaluate quantitatively the ability of longitudinally oriented poly(L-lactide-co-D,L-lactide) scaffolds with or without growth factors to promote bone healing. BMP-2and TGF-beta 3, combined with RGD-alginate hydrogel, were co-delivered to femoral defects within the polymer scaffolds at a dose previously shown to synergistically induce ectopic mineralization. A novel modular composite implant design was used to achieve reproducible stable fixation, provide a window for longitudinal in vivo micro-CT monitoring of 3D bone ingrowth, and allow torsional biomechanical testing of functional integration. Sequential micro-CT analysis showed that bone ingrowth increased significantly between 4 and 16 weeks for the scaffold-treated defects with or without growth factors, but no increase with time was observed in empty defect controls. Treatment with scaffold alone improved defect stability at 16 weeks compared to nontreatment, but did not achieve bone union or restoration of mechanical function. Augmentation of scaffolds with BMP-2 and TGF-beta 3 significantly increased bone formation at both 4 and 16 weeks compared to nontreatment, but only produced bone bridging of the defect region in two of six cases. Histological evaluation indicated that bone formed first at the periphery of the scaffolds, followed by more limited mineral deposition within the scaffold interior, suggesting that the cells participating in the initial healing response were primarily derived from periosteum. This study introduces a challenging segmental defect model that facilitates quantitative evaluation of strategies to repair critically sized bone defects. Healing of the defect region was improved by implanting structural polymeric scaffolds infused with growth factors incorporated within RGD-alginate. However, functional integration of the constructs appeared limited by continued presence of slow-degrading scaffolds and suboptimal dose or delivery of osteoinductive signals. (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.