Fan Changjiang, Wang Dong-An
Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457.
Macromol Biosci. 2015 Apr;15(4):535-45. doi: 10.1002/mabi.201400453. Epub 2015 Jan 2.
One bottleneck in tissue regeneration with hydrogel scaffolds is the limited understanding of the crucial factors for controlling hydrogel's physical microenvironments to regulate cell fate. Here, the effects of permeability and living space of hydrogels on encapsulated cells' behavior were evaluated, respectively. Three model hydrogel-based constructs are fabricated by using photo-crosslinkable hyaluronic acid as precursor and chondrocytes as model cell type. The better permeable hydrogels facilitate better cell viability and rapid proliferation, which lead to increased production of extracellular matrix (ECM), e.g. collagen, glycosaminoglycan. By prolonged culture, nano-sized hydrogel networks inhibit neo-tissue development, and the presence of macro-porous living spaces significantly enhance ECM deposition via forming larger cell clusters and eventually induce formation of scaffold-free neo-tissue islets. The results of this work demonstrate that the manipulation and optimization of hydrogel microenvironments, namely permeability and living space, are crucial to direct cell fate and neo-tissue formation.
水凝胶支架用于组织再生的一个瓶颈是，对于控制水凝胶物理微环境以调节细胞命运的关键因素了解有限。在此，分别评估了水凝胶的渗透性和生存空间对包封细胞行为的影响。使用可光交联的透明质酸作为前体，软骨细胞作为模型细胞类型，制备了三种基于水凝胶的模型构建体。渗透性较好的水凝胶有利于更好的细胞活力和快速增殖，这会导致细胞外基质（ECM）如胶原蛋白、糖胺聚糖的产量增加。通过长时间培养，纳米尺寸的水凝胶网络会抑制新组织的发育，而大孔生存空间的存在则通过形成更大的细胞簇显著增强ECM沉积，并最终诱导无支架新组织胰岛的形成。这项工作的结果表明，对水凝胶微环境（即渗透性和生存空间）的操控和优化对于引导细胞命运和新组织形成至关重要。
