Abstract

Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair. Collagen biomaterials that can host endothelial cells represent promising tools for the vascularization of engineered tissues. Three-dimensional collagen scaffolds possessing controlled architecture and mechanical stiffness are obtained through freeze–drying of collagen suspensions, followed by chemical cross-linking which maintains their stability. However, cross-linking scaffolds renders their biological activity suboptimal for many cell types, including human umbilical vein endothelial cells (HUVECs), by inhibiting cell–collagen interactions. Here, we have improved crucial HUVEC interactions with such cross-linked collagen biomaterials by covalently coupling combinations of triple-helical peptides (THPs). These are ligands for collagen-binding cell-surface receptors (integrins or discoidin domain receptors) or secreted proteins (SPARC and von Willebrand factor). THPs enhanced HUVEC adhesion, spreading and proliferation on 2D collagen films. THPs grafted to 3D-cross-linked collagen scaffolds promoted cell survival over seven days. This study demonstrates that THP-functionalized collagen scaffolds are promising candidates for hosting endothelial cells with potential for the production of vascularized engineered tissues in regenerative medicine applications.

中文翻译：

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用三螺旋肽功能化的胶原支架支持 3D HUVEC 培养

 抽象的

为细胞提供结构和生物支持的多孔生物材料在组织工程和基于细胞的组织修复疗法中具有巨大的潜力。可以容纳内皮细胞的胶原生物材料代表了工程组织血管化的有前途的工具。通过冷冻干燥胶原悬浮液，然后进行化学交联以保持其稳定性，获得具有受控结构和机械刚度的三维胶原支架。然而，交联支架通过抑制细胞与胶原蛋白的相互作用，使其生物活性对于许多细胞类型来说不是最佳的，包括人脐静脉内皮细胞（HUVEC）。在这里，我们通过三螺旋肽（THP）的共价偶联组合改善了 HUVEC 与此类交联胶原生物材料的关键相互作用。这些是胶原蛋白结合细胞表面受体（整联蛋白或盘状蛋白结构域受体）或分泌蛋白（SPARC 和冯维勒布兰德因子）的配体。 THP 增强了 HUVEC 在 2D 胶原蛋白膜上的粘附、扩散和增殖。移植到 3D 交联胶原蛋白支架上的 THP 可促进细胞存活超过 7 天。这项研究表明，THP 功能化胶原支架是承载内皮细胞的有前途的候选者，具有在再生医学应用中生产血管化工程组织的潜力。