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Designing a bioactive scaffold from coassembled collagen–laminin short peptide hydrogels for controlling cell behaviour

机译:从共组合的胶原蛋白短肽水凝胶中设计生物活性支架以控制细胞行为

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Synthetic bioactive hydrogels have been widely recognized as key elements of emerging strategies for tissue engineering. The complex hierarchical structure and chemical composition of the natural ECM inspires us to design multi-component ECM mimics that have potential applications in biomedicine. Taking inspiration from natural proteins, we hypothesized that designing a multi-component synthetic matrix based on short ECM derived peptides will be highly beneficial for providing a functional scaffold, which still remains a challenge in the field of biomaterials. For the proof of concept, we designed a composite hydrogel scaffold inspired by the two essential components of native ECM, i.e. collagen and laminin, which play diverse roles in supporting cell growth. To the best of our knowledge, we have designed the shortest collagen inspired peptide sequence i.e. Nap-FFGSO, which has propensity to self-assemble in the presence of short laminin mimetic peptides. Interestingly, only 10% w/w of laminin peptides was sufficient to provide nucleation and growth of the nanostructures in the collagen inspired peptide and induces further self-assembly to create higher order structures. Such a nucleation and growth mechanism can trigger gelation in the collagen inspired peptides, which otherwise failed to form a gel under physiological conditions. We could achieve similar complexity in the designed matrix through utilization of simple non-covalent interactions, rather than covalent synthetic methodologies to create a dual functional matrix from the non-gelator collagen inspired peptide. The nanofibrous morphology generated through co-assembly can essentially mimic the structure and function of natural ECM, which enables the scaffold to communicate with cells through biochemical signals and promote cell growth, adhesion, proliferation and migration. We envisage that this structural mimicry of a native collagen fibrillar network using such a short peptide sequence can lead to new opportunities for developing next generation functional materials. The strategy of supramolecular assembly using multiple components could develop a plethora of viable biomaterials under physiological conditions.
机译:合成生物活性水凝胶被广泛认识为组织工程的新出现策略的关键要素。自然ECM的复杂层次结构和化学成分激励我们设计具有生物医学中具有潜在应用的多组分ECM模拟。从天然蛋白质中汲取灵感,我们假设基于短ECM衍生的肽的设计多组分合成基质对于提供功能性支架,这仍然是生物材料领域的挑战。对于概念证明,我们设计了由天然ECM的两个基本组分的复合水凝胶支架,即胶原蛋白和层粘连蛋白,这在支持细胞生长方面发挥不同的作用。据我们所知,我们设计了最短的胶原蛋白灵感的肽序列I.E.NAP-FFGSO,其在短玻璃蛋白模拟肽存在下具有自组装的倾向。有趣的是,只有10%w / w的层粘蛋白肽足以提供胶原蛋白的肽中纳米结构的成核和生长,并诱导进一步的自组装以产生更高阶结构。这种成核和生长机制可以引发胶原蛋白的激发肽中的凝胶化,否则在生理条件下未能形成凝胶。我们可以通过利用简单的非共价相互作用,而不是共价合成方法来实现类似的复杂性,而不是共价合成方法,以从非胶凝胶胶原蛋白的灵感肽产生双官能基质。通过共组件产生的纳米纤维形态基本上可以模仿自然ECM的结构和功能,这使得支架能够通过生物化学信号与细胞连通,并促进细胞生长,粘附,增殖和迁移。我们设想使用这种短肽序列的本地胶原纤维结合网络的这种结构模拟可以导致开发下一代功能材料的新机会。使用多种组分的超分子组件的策略可以在生理条件下发育过多的可行生物材料。

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