Injectable and Thermosensitive Soluble Extracellular Matrix and Methylcellulose Hydrogels for Stem Cell Delivery in Skin Wounds

Extracellular matrix (ECM) provides structural support and biochemical cues for tissue development and regeneration. Here we report a thermosensitive hydrogel composed of soluble ECM (sECM) and methylcellulose (MC) for injectable stem cell delivery. The sECM was prepared by denaturing solid ECM extracted from human adipose tissue and then blended with a MC solution. At low temperatures, the sECM-MC solution displayed a viscous solution state in which the loss modulus (G″) was predominant over the storage modulus (G'). With increasing temperature, G' increased dramatically and eventually exceeded G″ around 34 °C, characteristic of the transition from a liquid-like state to an elastic gel-like state. After a single injection of the stem cell-embedded hydrogel in full thickness cutaneous wound, the wound healed rapidly through re-epithelialization and neovascularization with minimum scar formation. The overall results suggest that in-situ-forming sECM-MC hydrogels are a promising injectable vehicle for stem cell delivery and tissue regeneration.