Repair of bone defects using synthetic mimetics of collagenous extracellular matrices
Repair of bone defects using synthetic mimetics of collagenous extracellular matrices
复制标题
DOI：
10.1038/nbt818
复制
发表时间：
2003-05-01
影响因子：
46.9
通讯作者：
Hubbell, JA
中科院分区：
文献类型：
--
作者：
Lutolf, MR;Weber, FE;Hubbell, JA
我们已经设计了基于聚乙二醇（PEG）的合成水凝胶作为原位骨再生的细胞向内生长基质。这些网络包含细胞粘附的侧链寡肽配体（RGDSP）和基质金属蛋白酶（MMP）的底物的组合作为PEG链之间的接头。原代人成纤维细胞被证明在这些基质中迁移的整合素和MMP依赖性机制。用于将重组人骨形态发生蛋白-2（rhBMP-2）递送到大鼠颅骨关键大小缺损部位的凝胶完全被细胞浸润，并在5周内重塑为骨组织。骨再生取决于基质及其结构的蛋白水解敏感性。凝胶的细胞介导的蛋白水解侵袭性和rhBMP-2的包埋导致有效和高度局部化的骨再生。
We have engineered synthetic poly(ethylene glycol) (PEG)-based hydrogels as cell-ingrowth matrices for in situ bone regeneration. These networks contain a combination of pendant oligopeptide ligands for cell adhesion (RGDSP) and substrates for matrix metalloproteinase (MMP) as linkers between PEG chains. Primary human fibroblasts were shown to migrate within these matrices by integrin- and MMP-dependent mechanisms. Gels used to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) to the site of critical-sized defects in rat crania were completely infiltrated by cells and were remodeled into bony tissue within five weeks. Bone regeneration was dependent on the proteolytic sensitivity of the matrices and their architecture. The cell-mediated proteolytic invasiveness of the gels and entrapment of rhBMP-2 resulted in efficient and highly localized bone regeneration.