The delivery of chemotactic signaling molecules via customized biomaterials can effectively guide the migration of cells to improve the regeneration of damaged or diseased tissues. Here, we present a novel biohybrid hydrogel system containing two different sulfated glycosaminoglycans (sGAG)/sGAG derivatives, namely either a mixture of short heparin polymers (Hep-Mal) or structurally defined nona-sulfated tetrahyaluronans (9s-HA4-SH), to precisely control the release of charged signaling molecules. The polymer networks are described in terms of their negative charge, i.e. the anionic sulfate groups on the saccharides, using two parameters, the integral density of negative charge and the local charge distribution (clustering) within the network. The modulation of both parameters was shown to govern the release characteristics of the chemotactic signaling molecule SDF-1 and allows for seamless transitions between burst and sustained release conditions as well as the precise control over the total amount of delivered protein. The obtained hydrogels with well-adjusted release profiles effectively promote MSC migration in vitro and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.

中文翻译：

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调整生物混合水凝胶基质的网络电荷以调节 SDF-1 的释放

通过定制的生物材料传递趋化信号分子可以有效地引导细胞迁移，从而促进受损或病变组织的再生。在这里，我们提出了一种新的生物混合水凝胶系统，其中包含两种不同的硫酸化糖胺聚糖 (sGAG)/sGAG 衍生物，即短肝素聚合物 (Hep-Mal) 或结构上定义的九硫酸化四透明质酸 (9s-HA4-SH) 的混合物，以精确控制带电信号分子的释放。聚合物网络根据它们的负电荷，即糖类上的阴离子硫酸盐基团，使用两个参数来描述，负电荷的积分密度和网络内的局部电荷分布（簇）。两个参数的调节被证明可以控制趋化信号分子 SDF-1 的释放特性，并允许在爆发和持续释放条件之间进行无缝转换，以及精确控制所传递的蛋白质的总量。获得的具有良好调节释放曲线的水凝胶有效促进 MSC 迁移体外并在骨修复和伤口愈合方面成为新治疗方式的有希望的候选者。