Bioactive hydrogels based on Designer Collagens
Bioactive hydrogels based on Designer Collagens
复制标题
DOI：
10.1016/j.actbio.2010.05.002
复制
发表时间：
2010-10-01
影响因子：
9.7
通讯作者：
Hoeoek, M.
中科院分区：
文献类型：
--
作者：
Cosgriff-Hernandez, E.;Hahn, M. S.;Hoeoek, M.
设计胶原蛋白基于链球菌胶原蛋白样 (Scl) 蛋白，该蛋白形成类似于哺乳动物胶原蛋白的三螺旋，但不聚集血小板。与胶原蛋白上众多的细胞结合位点相反，来自化脓性链球菌血清型 M28 的 Scl2 不包含任何已知的细胞结合位点，因此在细胞相互作用方面提供了空白。在当前的研究中，Scl2 蛋白被修饰为包含与 α 1 和/或 α 2 整合素亚基相互作用的受体结合基序。修饰的 Scl2 蛋白已被证明可以介导内皮细胞 (EC) 和平滑肌的分化细胞（SMC）通过这些整联蛋白粘附，并保留“亲本”Scl2的非血小板聚集特性。相对于SMC，选择性结合EC的抗血栓支架对于血管修复或置换来说是理想的。尽管这些Scl蛋白在血管应用中具有潜力，但由于Scl蛋白无法组装成稳定的三维网络，该重组蛋白家族的效用目前仅限于涂层。为了解决这一限制，Scl2蛋白被功能化表征研究证实，Scl2 蛋白的功能化不会破坏三螺旋构象、整合素结合或细胞粘附。通过将功能化的 Scl2 蛋白与聚乙二醇二丙烯酸酯 (PEGDA) 结合并进行光交联，制备了生物活性水凝胶。 EC 和 SMC 粘附研究证实了由于选择性整合素与所研究的两个受体结合基序结合而产生的细胞特异性粘附。这些结果凸显了这种新型生物材料平台在开发改进的组织工程血管移植物方面的潜力由 Elsevier Ltd 代表 Acta Materialia Inc 出版
Designer Collagens are based on streptococcal collagen-like (Scl) proteins that form a triple helix similar to mammalian collagens but that are non-platelet aggregating. In contrast to the numerous cell-binding sites on collagen, Scl2 from Streptococcus pyogenes serotype M28 does not contain any known cell-binding sites and thus provides a blank slate in terms of cellular interactions In the current study, Scl2 protein was modified to include receptor binding motifs that interact with alpha 1 and/or alpha 2 integrin subunits The modfied Scl2 proteins have been demonstrated to mediate differential endothelial cell (EC) and smooth muscle cell (SMC) adhesion via these integrins and to retain the non-platelet aggregating properties of the "parent" Scl2 Thromboresistant scaffolds which selectively bind ECs vs SMCs would be desirable for vascular repair or replacementDespite the potential of these Scl proteins in vascular applications, the utility of this recombinant protein family is currently limited to coatings due to the inability of Scl proteins to assemble into stable three-dimensional networks To address this limitation, the Scl2 proteins were functionalized with photocrosslinking sites to enable incorporation into a hydrogel matrix Characterization studies confirmed that the functionalization of the Scl2 proteins did not disrupt triple helix conformation, integrin binding or cell adhesion Bioactive hydrogels were fabricated by combining the functionalized Scl2 proteins with poly(ethylene glycol) diacrylate (PEGDA) and photocrosslinking. EC and SMC adhesion studies confirmed cell-specific adhesion due to selective integrin binding to the two receptor binding motifs investigated These results serve to highlight the potential of this novel biomaterial platform in the development of improved tissue engineered vascular grafts Published by Elsevier Ltd on behalf of Acta Materialia Inc