Hydrogels produced by self-assembling peptides are intrinsically biocompatible and thus appropriate for many biomedical purposes. Their application field may be even made wider by reducing the softness and improving the hydrogel mechanical properties through cross-linking treatments. To this aim, modifications of EAK16-II sequence by including Cys residues in its sequence were here investigated in order to obtain hydrogels cross-linkable through a disulfide bridge. Two sequences, namely, C-EAK and C-EAK-C, that contain Cys residues at the N-terminus or at both ends were characterized. Fiber-forming abilities and biological and dynamic mechanical properties were explored before and after the oxidative treatment. In particular, the oxidized version of C-EAK presents a good cell viability and sustains osteoblast proliferation. Furthermore, molecular dynamics (MD) simulations on monomeric and assembled forms of the peptides were performed. MD simulations explained how a specific Cys functionalization was better than the other one. In particular, the results suggested that EAK16-II functionalization with a single Cys residue, instead of two, together with biocompatible cross-linking may be considered an intriguing strategy to obtain a support with better dynamic mechanical properties and biological performances.

中文翻译：

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通过二硫键交联的EAK水凝胶：Cys数和位置与性能匹配

由自组装肽产生的水凝胶本质上是生物相容的，因此适合于许多生物医学目的。通过降低柔软度并通过交联处理改善水凝胶的机械性能，甚至可以扩大其应用领域。为了这个目的，本文研究了通过在其序列中包含Cys残基来修饰EAK16-II序列，以获得可通过二硫键交联的水凝胶。鉴定了两个序列，即C-EAK和C-EAK-C，其在N端或两端均含有Cys残基。在氧化处理之前和之后，研究了纤维形成能力以及生物学和动态力学性能。尤其是，C-EAK的氧化形式具有良好的细胞活力，并能维持成骨细胞的增殖。此外，对肽的单体形式和组装形式进行了分子动力学（MD）模拟。MD模拟解释了特定的Cys功能性如何比另一个更好。特别地，结果表明，用单个Cys残基代替两个残基的EAK16-II功能化以及生物相容性交联可被认为是一种获得具有更好动态力学性能和生物学性能的载体的有趣策略。