Müller Monica Z, Bernero Margherita, Xie Chang, Qiu Wanwan, Oggianu Esteban, Rabut Lucie, Michaels Thomas C T, Style Robert W, Müller Ralph, Qin Xiao-Hua
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
Bringing Materials to Life Initiative, ETH Zurich, Zurich, Switzerland.
Nat Commun. 2025 May 27;16(1):4923. doi: 10.1038/s41467-025-60113-9.
Microporous scaffolds facilitate solute transport and cell-material interactions, but materials allowing for spatiotemporally controlled pore formation in aqueous solutions are lacking. Here, we propose cell-guiding microporous hydrogels by photopolymerization-induced phase separation (PIPS) as instructive scaffolding materials for 3D cell culture. We formulate a series of PIPS resins consisting of two ionic polymers (norbornene-functionalized polyvinyl alcohol, dextran sulfate), di-thiol linker and water-soluble photoinitiator. Before PIPS, the polymers are miscible. Upon photocrosslinking, they demix due to the increasing molecular weight and form a microporous hydrogel. The pore size is tunable in the range of 2-40 μm as a function of light intensity, polymer composition and molecular charge. Unlike conventional methods to fabricate porous hydrogels, our PIPS approach allows for in situ light-controlled pore formation in the presence of living cells. We demonstrate that RGD-functionalized microporous hydrogels support high cell viability (>95%), fast cell spreading and 3D morphogenesis. As a proof-of-concept, these hydrogels also enhance the osteogenic differentiation of human mesenchymal stromal cells, matrix mineralization and collagen secretion. Collectively, this study presents a class of cell-guiding microporous hydrogels by PIPS which may find applications in complex tissue engineering.
微孔支架有助于溶质运输和细胞与材料的相互作用，但缺乏能在水溶液中实现时空可控成孔的材料。在此，我们提出通过光聚合诱导相分离（PIPS）制备细胞导向微孔水凝胶，作为用于三维细胞培养的指导性支架材料。我们配制了一系列由两种离子聚合物（降冰片烯功能化聚乙烯醇、硫酸葡聚糖）、二硫醇连接剂和水溶性光引发剂组成的PIPS树脂。在进行PIPS之前，这些聚合物是可混溶的。光交联后，它们因分子量增加而发生相分离，形成微孔水凝胶。孔径可在2 - 40μm范围内根据光强度、聚合物组成和分子电荷进行调节。与制备多孔水凝胶的传统方法不同，我们的PIPS方法允许在活细胞存在的情况下进行原位光控成孔。我们证明，RGD功能化微孔水凝胶支持高细胞活力（>95%）、快速细胞铺展和三维形态发生。作为概念验证，这些水凝胶还能增强人间充质基质细胞的成骨分化、基质矿化和胶原蛋白分泌。总的来说，本研究提出了一类通过PIPS制备的细胞导向微孔水凝胶，其可能在复杂组织工程中得到应用。
