Kühn Sebastian, Freyse Joanna, Atallah Passant, Rademann Jörg, Freudenberg Uwe, Werner Carsten
Leibniz Institute of Polymer Research Dresden (IPF), Max Bergmann Center of Biomaterials Dresden (MBC), Hohe Str. 6, D-01069 Dresden, Germany.
Institute of Pharmacy, Medicinal Chemistry, Freie Universität Berlin, Königin-Luise-Strasse 2+4, D-14195 Berlin, Germany.
Biol Chem. 2021 Jul 5;402(11):1453-1464. doi: 10.1515/hsz-2021-0175. Print 2021 Oct 26.
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 and emerge as promising candidates for new treatment modalities in the context of bone repair and wound healing.
通过定制生物材料递送趋化信号分子可以有效地引导细胞迁移，以改善受损或患病组织的再生。在此，我们展示了一种新型生物杂交水凝胶系统，其包含两种不同的硫酸化糖胺聚糖（sGAG）/sGAG衍生物，即短肝素聚合物混合物（Hep-Mal）或结构明确的九硫酸化四聚透明质酸（9s-HA4-SH），以精确控制带电信号分子的释放。聚合物网络通过两个参数来描述其负电荷，即糖类上的阴离子硫酸基团，这两个参数分别是负电荷的积分密度和网络内的局部电荷分布（聚集）。结果表明，对这两个参数的调节可控制趋化信号分子SDF-1的释放特性，并允许在突释和缓释条件之间实现无缝过渡，以及对递送蛋白质的总量进行精确控制。所获得的具有良好调节释放曲线的水凝胶有效地促进了间充质干细胞迁移，并成为骨修复和伤口愈合背景下新治疗方式的有希望的候选者。
