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<p>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 (&gt;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.</p>

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Cell-guiding microporous hydrogels by photopolymerization-induced phase separation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月27日

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  • Monica Z. Müller,
  • Margherita Bernero,
  • Chang Xie,
  • Wanwan Qiu,
  • Esteban Oggianu,
  • Lucie Rabut,
  • Thomas C. T. Michaels,
  • Robert W. Style,
  • Ralph Müller,
  • Xiao-Hua Qin

摘要

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.