Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069, Dresden, Germany.
Leibniz-Institut für Polymerforschung Dresden e.V., Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069, Dresden, Germany; Technische Universität Dresden, Center for Regenerative Therapies Dresden and Cluster of Excellence Physics of Life, 01062, Dresden, Germany.
Biomaterials. 2021 Nov;278:121170. doi: 10.1016/j.biomaterials.2021.121170. Epub 2021 Oct 1.
Macroporous cryogels have recently gained increasing interest for the controlled administration of signaling proteins in tissue engineering due to an advantageous combination of material properties. However, most of the previously reported cryogel systems did not allow for tunable, sustained protein release. We therefore designed a set of ready-to-use multi-armed polyethylene glycol (starPEG)-heparin cryogel systems containing different amounts of the protein-affine glycosaminoglycan component heparin to enable systematically tunable long-term delivery of different signaling proteins without affecting other cell-instructive properties. Experimental data and mathematical modeling indicate that the macroporous structure causes local differences in the concentration of proteins released into the pores and in the surrounding of the cryogels. As a proof-of-concept for their ready-to-use potential, cryogels pre-functionalized with signaling proteins and cell adhesion-peptides were demonstrated to induce the neuronal differentiation of colonizing pheochromocytoma cells. The elaborated approach opens up new perspectives for cryogels as easily storable and applicable systems for the precision delivery of signaling proteins.
大孔冷冻凝胶由于其优越的材料性能，最近在组织工程中用于控制信号蛋白的给药而受到越来越多的关注。然而，之前报道的大多数冷冻凝胶系统都不能进行可调节的、持续的蛋白质释放。因此，我们设计了一系列即用型多臂聚乙二醇（星形 PEG）-肝素冷冻凝胶系统，其中含有不同量的蛋白质亲和性糖胺聚糖成分肝素，以实现系统地调节不同信号蛋白的长期释放，而不影响其他细胞指令性特性。实验数据和数学模型表明，大孔结构导致释放到孔中和冷冻凝胶周围的蛋白质浓度存在局部差异。作为其即用型潜力的概念验证，用信号蛋白和细胞黏附肽预先功能化的冷冻凝胶被证明可以诱导定植嗜铬细胞瘤细胞的神经元分化。所阐述的方法为冷冻凝胶作为可精确输送信号蛋白的易于储存和适用系统开辟了新的前景。
