Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 330-714, Republic of Korea; Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan 330-714, Republic of Korea.
Department of Biochemistry, College of Medicine, Inha University, Incheon, Republic of Korea.
Biomaterials. 2015 Jul;56:46-57. doi: 10.1016/j.biomaterials.2015.03.022. Epub 2015 Apr 15.
Biomaterial surface design with biomimetic proteins holds great promise for successful regeneration of tissues including bone. Here we report a novel proteinaceous hybrid matrix mimicking bone extracellular matrix that has multifunctional capacity to promote stem cell adhesion and osteogenesis with excellent stability. Osteocalcin-fibronectin fusion protein holding collagen binding domain was networked with fibrillar collagen, featuring bone extracellular matrix mimic, to provide multifunctional and structurally-stable biomatrices. The hybrid protein, integrated homogeneously with collagen fibrillar networks, preserved structural stability over a month. Biological efficacy of the hybrid matrix was proven onto tethered surface of biopolymer porous scaffolds. Mesenchymal stem cells quickly anchored to the hybrid matrix, forming focal adhesions, and substantially conformed to cytoskeletal extensions, benefited from the fibronectin adhesive domains. Cells achieved high proliferative capacity to reach confluence rapidly and switched to a mature and osteogenic phenotype more effectively, resulting in greater osteogenic matrix syntheses and mineralization, driven by the engineered osteocalcin. The hybrid biomimetic matrix significantly improved in vivo bone formation in calvarial defects over 6 weeks. Based on the series of stimulated biological responses in vitro and in vivo the novel hybrid proteinaceous composition will be potentially useful as stem cell interfacing matrices for osteogenesis and bone regeneration.
仿生蛋白质的生物材料表面设计为包括骨骼在内的组织的成功再生带来了巨大的希望。在这里，我们报告了一种新型的蛋白质杂化基质，模拟骨细胞外基质，具有多功能能力，可促进干细胞黏附和成骨作用，且具有极好的稳定性。具有胶原结合结构域的骨钙素-纤维连接蛋白融合蛋白与纤维状胶原交联，形成具有仿生功能和结构稳定性的生物材料。该杂化蛋白与胶原纤维网络均匀整合，在一个月以上的时间内保持结构稳定。该杂化基质的生物学功效已在生物聚合物多孔支架的固着表面上得到证明。间充质干细胞迅速锚定在杂化基质上，形成粘着斑，并显著顺应细胞骨架延伸，得益于纤维连接蛋白的黏附结构域。细胞表现出高增殖能力，能迅速达到融合，并能更有效地向成熟的成骨表型转化，从而导致更多的成骨基质合成和矿化，这是由工程化的骨钙素驱动的。在 6 周的颅骨缺损中，该杂化仿生基质显著促进了体内骨形成。基于体外和体内一系列刺激的生物学反应，这种新型的蛋白质杂化组成物有望成为用于成骨和骨再生的干细胞界面基质。
