Cell-Free Hydrogel System Based on a Tissue-Specific Extracellular Matrix for In Situ Adipose Tissue Regeneration

Well-designed scaffolds provide appropriate niches that can effectively recruit host cells and induce differentiation of recruited cells into the desired cell types, facilitating in situ tissue regeneration. Here we report a tissue-specific extracellular matrix (ECM) hydrogel composed of adipose-derived soluble ECM (sECM) and methylcellulose (MC) as a cell-free scaffold system for adipose tissue regeneration. The sECM MC hydrogels showed a thermosensitive sol-gel phase transition and rapidly formed a soft hydrogel with a stiffness of 3.8 kPa at body temperature. An in vivo study showed that the sECM MC hydrogel facilitated the infiltration of host cell populations, particularly adipose-derived stem cells (ASCs) and adipose tissue macrophages (ATMs) that directly contribute to the adipose tissue regeneration. Moreover, the hydrogel significantly enhanced host-derived adipogenesis and angiogenesis without exogenous cells or bioactive molecules. Our results indicate that the sECM MC hydrogels provide mechanical and biochemical cues for host-derived adipose regeneration. Overall, the sECM MC hydrogels are a highly promising cell-free therapeutic approach for in situ adipose tissue regeneration.