PDF(Pubmed)
Abstract：
Hydrogels have emerged as a promising class of extracellular matrix (ECM)-mimicking materials in regenerative medicine. Here, we briefly describe current state-of-the-art of ECM-mimicking hydrogels, ranging from natural to hybrid to completely synthetic versions, giving the prelude to the importance of supramolecular interactions to make true ECM mimics. The potential of supramolecular interactions to create ECM mimics for cell culture is illustrated through a focus on two different supramolecular hydrogel systems, both developed in our laboratories. We use some recent, significant findings to present important design principles underlying the cell-material interaction. To achieve cell spreading, we propose that slow molecular dynamics (monomer exchange within fibers) is crucial to ensure the robust incorporation of cell adhesion ligands within supramolecular fibers. Slow bulk dynamics (stress-relaxation─fiber rearrangements, τ1/2 ≈ 1000 s) is required to achieve cell spreading in soft gels (<1 kPa), while gel stiffness overrules dynamics in stiffer gels. Importantly, this resonates with the findings of others which specialize in different material types: cell spreading is impaired in case substrate relaxation occurs faster than clutch binding and focal adhesion lifetime. We conclude with discussing considerations and limitations of the supramolecular approach as well as provide a forward thinking perspective to further understand supramolecular hydrogel-cell interactions. Future work may utilize the presented guidelines underlying cell-material interactions to not only arrive at the next generation of ECM-mimicking hydrogels but also advance other fields, such as bioelectronics, opening up new opportunities for innovative applications.
摘要：
水凝胶已成为再生医学中一类有前途的细胞外基质（ECM）模拟材料。这里,我们简要描述了当前的ECM模拟水凝胶的最新技术，从天然到混合到完全合成的版本，给出了超分子相互作用的重要性，使真正的ECM模拟的序幕。通过对两种不同的超分子水凝胶系统的关注，说明了超分子相互作用为细胞培养创建ECM模拟物的潜力。都是在我们的实验室开发的.我们用一些最近的，提出细胞-物质相互作用的重要设计原则的重要发现。为了实现细胞扩散，我们认为，缓慢的分子动力学（纤维内的单体交换）对于确保细胞粘附配体在超分子纤维内的稳固结合至关重要。缓慢的整体动力学(应力松弛--纤维重排，τ1/2≈1000s）是在软凝胶（<1kPa）中实现细胞扩散所必需的，而凝胶刚度超过了刚性凝胶中的动力学。重要的是,这与其他专门研究不同材料类型的研究结果相一致:如果底物松弛发生得比离合器结合和病灶粘附寿命更快，细胞扩散会受到损害。最后，我们讨论了超分子方法的考虑因素和局限性，并为进一步理解超分子水凝胶-细胞相互作用提供了前瞻性的思考视角。未来的工作可能会利用所提出的指导原则作为细胞-材料相互作用的基础，不仅可以实现下一代ECM模拟水凝胶，还可以推进其他领域。比如生物电子学，为创新应用开辟新的机遇。
