B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, Arnoldstraße 18, 01307, Dresden, Germany.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Fetscherstraße 105, 01307, Dresden, Germany.
Adv Mater. 2018 May;30(22):e1706100. doi: 10.1002/adma.201706100. Epub 2018 Apr 16.
Combinatorial screening represents a promising strategy to discover biomaterials for tailored cell culture applications. Although libraries incorporating different biochemical cues have been investigated, few simultaneously recapitulate relevant biochemical, physical, and dynamic features of the extracellular matrix (ECM). Here, a noncovalent system based on liquid-liquid phase separation (coacervation) and gelation mediated by glycosaminoglycan (GAG)-peptide interactions is reported. Multiple biomaterial libraries are generated using combinations of sulfated glycosaminoglycans and poly(ethylene glycol)-conjugated peptides. Screening these biomaterials reveals preferred biomatrices for the attachment of six cell types, including primary mesenchymal stromal cells (MSCs) and primary neural precursor cells (NPCs). Incorporation of GAGs sustains the expansion of all tested cell types comparable to standard cell culture surfaces, while osteogenic differentiation of MSC and neuronal differentiation of NPC are promoted on chondroitin and heparan biomatrices, respectively. The presented noncovalent system provides a powerful tool for developing tissue-specific ECM mimics.
组合筛选代表了一种有前途的策略，可以发现用于定制细胞培养应用的生物材料。尽管已经研究了包含不同生化线索的文库，但很少有文库同时再现细胞外基质 (ECM) 的相关生化、物理和动态特征。在这里，报道了一种基于液-液相分离（凝聚）和糖胺聚糖 (GAG)-肽相互作用介导的凝胶化的非共价系统。使用硫酸化糖胺聚糖和聚（乙二醇）-缀合肽的组合生成了多个生物材料文库。筛选这些生物材料揭示了六种细胞类型（包括原代间充质基质细胞 (MSC) 和原代神经前体细胞 (NPC)) 附着的首选生物基质。GAG 的掺入可维持所有测试细胞类型的扩增，与标准细胞培养表面相当，而软骨素和肝素生物基质则分别促进 MSC 的成骨分化和 NPC 的神经元分化。所提出的非共价系统为开发组织特异性 ECM 模拟物提供了强大的工具。
