Kumar Vivek A, Taylor Nichole L, Jalan Abhishek A, Hwang Lyahn K, Wang Benjamin K, Hartgerink Jeffery D
Department of Chemistry, Department of Bioengineering, Rice University , Houston, Texas 77030, United States.
Biomacromolecules. 2014 Apr 14;15(4):1484-90. doi: 10.1021/bm500091e. Epub 2014 Apr 2.
Collagen is a major component of the extracellular matrix and plays a wide variety of important roles in blood clotting, healing, and tissue remodeling. Natural, animal derived, collagen is used in many clinical applications but concerns exist with respect to its role in inflammation, batch-to-batch variability, and possible disease transfection. Therefore, development of synthetic nanomaterials that can mimic the nanostructure and properties of natural collagen has been a heavily pursued goal in biomaterials. Previously, we reported on the design and multihierarchial self-assembly of a 36 amino acid collagen mimetic peptide (KOD) that forms nanofibrous triple helices that entangle to form a hydrogel. In this report, we utilize this nanofiber forming collagen mimetic peptide as a synthetic biomimetic matrix useful in thrombosis. We demonstrate that nanofibrous KOD synthetic collagen matrices adhere platelets, activate them (indicated by soluble P-selectin secretion), and clot plasma and blood similar to animal derived collagen and control surfaces. In addition to the thrombotic potential, THP-1 monocytes incubated with our KOD collagen mimetic showed minimal proinflammatory cytokine (TNF-α or IL-1β) production. Together, the data presented demonstrates the potential of a novel synthetic collagen mimetic as a hemostat.
胶原蛋白是细胞外基质的主要成分，在血液凝固、愈合和组织重塑中发挥着多种重要作用。天然的、动物来源的胶原蛋白被用于许多临床应用，但人们对其在炎症中的作用、批次间的变异性以及可能的疾病传播存在担忧。因此，开发能够模拟天然胶原蛋白纳米结构和特性的合成纳米材料一直是生物材料领域备受追求的目标。此前，我们报道了一种36个氨基酸的胶原蛋白模拟肽（KOD）的设计和多级自组装，该肽形成纳米纤维状三螺旋结构并相互缠绕形成水凝胶。在本报告中，我们将这种形成纳米纤维的胶原蛋白模拟肽用作血栓形成中有用的合成仿生基质。我们证明，纳米纤维状KOD合成胶原蛋白基质能够黏附血小板，激活血小板（通过可溶性P-选择素分泌来表明），并使血浆和血液凝结，类似于动物来源的胶原蛋白和对照表面。除了具有血栓形成潜力外，与我们的KOD胶原蛋白模拟物一起孵育的THP-1单核细胞显示出极低的促炎细胞因子（TNF-α或IL-1β）产生。综上所述，所呈现的数据证明了一种新型合成胶原蛋白模拟物作为止血剂的潜力。
