ArticleInternational journal of molecular sciences2026
Mechanically Soft Phase-Separated Gelatin/Hyaluronic Acid Hydrogels Support Long-Term Expansion of Human Mesenchymal Stem Cells While Preserving Multipotency.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Large-scale expansion of human mesenchymal stem cells (hMSCs) remains a major challenge due to the intrinsic trade-off between cell proliferation and the maintenance of multipotency in conventional culture systems. Stiff substrates, such as tissue culture polystyrene or rigid hydrogels, promote rapid proliferation but induce progressive loss of stemness, whereas very soft matrices preserve multipotency at the expense of cell growth. To overcome this limitation, we developed mechanically soft, phase-separated gelatin-phenol/hyaluronic acid-phenol (Gtn-Ph/HA-Ph) hydrogels with precisely controlled microstructures via enzyme-mediated crosslinking. These hydrogels consist of HA-rich, dot-like domains embedded within a continuous Gtn-rich network, allowing for independent tuning of stiffness and domain architecture. On single-component Gtn-Ph hydrogels, hMSC proliferation increased with substrate stiffness, whereas soft hydrogels with a storage modulus (
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