Modulated integrin signaling receptors of stem cells via ultra-soft hydrogel for promoting angiogenesis

Integrin is a widely distributed adhesion molecule on cell membrane surface, which plays a role in transferring mechanical properties signals of the extracellular matrix into cells during cell adhesion to the extracellular matrix. In this study, by introducing long-chain polyethylene glycol molecules that can be photo-crosslinked into gelatin chains, ultra-soft hydrogel that can simulate soft tissue in vivo is constructed and stimulated by "low matrix stiffness" of the integrin signaling pathway, to promote the vascularization function of stem cells. The storage modulus of the ultra-soft hydrogel at room temperature is as low as 3.24 ± 0.18 Pa and as high as 40.83 ± 1.32 Pa. In vitro experiments showed that the stiffness of hydrogel affects the activation of the phosphorylation of VEGFR by regulating the phosphorylation of integrin and further controls the activation of the ERK pathway, thus regulating the vascularization of ADSCs. In vivo experiments have proved that ADSCs encapsulated in PEG-Gel have excellent performance in repairing skin flaps. The ultra-soft hydrogel can promote the vascularization of ADSCs by activating the "extracellular matrix stiffness-integrin-VEGFR-ERK" regulatory pathway, which is a potential regenerative repair material for promoting the application of stem cells in skin flap repair.