Shepherd Jennifer, Bax Daniel, Best Serena, Cameron Ruth
Department of Materials Science and Metallurgy, University of Cambridge, Cambridge CB3 0FS, UK.
Materials (Basel). 2017 May 23;10(6):568. doi: 10.3390/ma10060568.
A significant body of research has considered collagen as a scaffold material for soft tissue regeneration. The main structural component of extra-cellular matrix (ECM), collagen's advantages over synthetic polymers are numerous. However, for applications where higher stiffness and stability are required, significant cross-linking may affect bioactivity. A carbodiimide (EDC) cross-linking route consumes carboxylate groups that are key to collagen's essential cell recognition motifs (GxOGER). Fibrinogen was considered as a promising additive as it plays a key role in the process of wound repair and contains RGD integrin binding sites which bind to a variety of cells, growth factors and cytokines. Fibrinogen's binding sites however, also contain the same carboxylate groups as collagen. We have successfully produced highly interconnected, porous collagen-fibrinogen scaffolds using a lyophilisation technique and micro-computed tomography demonstrated minimal influence of either fibrinogen content or cross-linking concentration on the scaffold structure. The specific biological effect of fibrinogen additions into cross-linked collagen are considered by using films as a model for the struts of bulk scaffolds. By considering various additions of fibrinogen to the collagen film with increasing degrees of cross-linking, this study demonstrates a significant biological advantage with fibrinogen addition across the cross-linking concentrations typically applied to collagen-based scaffolds.
大量研究将胶原蛋白视为软组织再生的支架材料。作为细胞外基质(ECM)的主要结构成分,胶原蛋白相对于合成聚合物具有诸多优势。然而,在需要更高硬度和稳定性的应用中,显著的交联可能会影响生物活性。碳二亚胺(EDC)交联途径会消耗对胶原蛋白至关重要的细胞识别基序(GxOGER)中的羧基。纤维蛋白原被认为是一种有前景的添加剂,因为它在伤口修复过程中起关键作用,并且含有与多种细胞、生长因子和细胞因子结合的RGD整合素结合位点。然而,纤维蛋白原的结合位点也含有与胶原蛋白相同的羧基。我们使用冻干技术成功制备了高度互连的多孔胶原蛋白 - 纤维蛋白原支架,微计算机断层扫描显示纤维蛋白原含量或交联浓度对支架结构的影响最小。通过将薄膜作为整体支架支柱的模型,研究了纤维蛋白原添加到交联胶原蛋白中的特定生物学效应。通过考虑在交联程度不断增加的情况下向胶原蛋白膜中添加不同量的纤维蛋白原,本研究表明,在通常应用于基于胶原蛋白的支架的交联浓度范围内,添加纤维蛋白原具有显著的生物学优势。