Reversible Thermoresponsive Hydrogel Fabricated from Natural Biopolymer for the Improvement of Critical Limb Ischemia by Controlling Release of Stem Cells

: Stem cells therapy is an effective treatment for critical limb ischemia diseases (CLI), but is limited to low cells retention and poor target release in severe ischemia tissues. Due to the notable feature of CLI, namely, the temperature of ischemia tissues decreases with the severity of the lesions, a thermoresponsive and reversible hydrogel based on methylcellulose-salt system encapsulating stem cells is facilely prepared and successfully achieved the goal of releasing stem cells in lower temperature areas. The investigations show that the thermogel presents notable biocompatibility, thermoresponsiveness, and cytoprotection. Furthermore, the combined transplantation of hydrogel and stem cells system effectively inhibits the fibrosis and muscular atrophy of lower limb ischemia, accelerates the recovery of lower limb blood flow, and promotes angiogenesis, indicating that the reversible thermogel can promote vascular repair by controlling the release of loaded stem cells in the treatment of CLI.