Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, Room 2314 IBB, Atlanta, GA 30332-0363, USA.
Sci Transl Med. 2010 Aug 18;2(45):45ra60. doi: 10.1126/scitranslmed.3001002.
Engineered biointerfaces covered with biomimetic motifs, including short bioadhesive ligands, are a promising material-based strategy for tissue repair in regenerative medicine. Potentially useful coating molecules are ligands for the integrins, major extracellular matrix receptors that require both ligand binding and nanoscale clustering for maximal signaling efficiency. We prepared coatings consisting of well-defined multimer constructs with a precise number of recombinant fragments of fibronectin (monomer, dimer, tetramer, and pentamer) to assess how nanoscale ligand clustering affects integrin binding, stem cell responses, tissue healing, and biomaterial integration. Clinical-grade titanium was grafted with polymer brushes that presented monomers, dimers, trimers, or pentamers of the alpha(5)beta(1) integrin-specific fibronectin III (7 to 10) domain (FNIII(7-10)). Coatings consisting of trimers and pentamers enhanced integrin-mediated adhesion in vitro, osteogenic signaling, and differentiation in human mesenchymal stem cells more than did surfaces presenting monomers and dimers. Furthermore, ligand clustering promoted bone formation and functional integration of the implant into bone in rat tibiae. This study establishes that a material-based strategy in which implants are coated with clustered bioadhesive ligands can promote robust implant-tissue integration.
用具有仿生图案的工程生物界面（包括短的生物黏附配体）覆盖，是再生医学中组织修复的一种很有前途的基于材料的策略。潜在有用的涂层分子是整合素的配体，整合素是主要的细胞外基质受体，其需要配体结合和纳米级聚集以实现最大的信号效率。我们制备了由具有精确数量的纤维连接蛋白（单体、二聚体、四聚体和五聚体）的重组片段组成的明确多聚体构建体涂层，以评估纳米级配体聚集如何影响整合素结合、干细胞反应、组织愈合和生物材料整合。临床级钛被接枝到聚合物刷上，聚合物刷上展示了特定于α(5)β(1)整合素的纤维连接蛋白 III（7 到 10）结构域（FNIII(7-10)）的单体、二聚体、三聚体或五聚体。由三聚体和五聚体组成的涂层比呈现单体和二聚体的表面更能增强体外整合素介导的黏附、成骨信号和人间充质干细胞的分化。此外，配体聚集促进了植入物在大鼠胫骨中的骨形成和功能整合。这项研究确立了一种基于材料的策略，即用聚集的生物黏附配体涂层植入物，可以促进植入物与组织的牢固整合。
