ECM‐Inspired Hydrogels with ADSCs Encapsulation for Rheumatoid Arthritis Treatment

Abstract Due to their intrinsic anti‐inflammatory and immunomodulatory properties, adipose‐derived stem cells (ADSCs) are explored as a promising alternative in treating rheumatoid arthritis (RA). To address the poor survival and function loss of directly injected stem cells, efforts in this area are focus on the generation of efficient cell delivery vehicles. Herein, a novel extracellular matrix (ECM)‐inspired injectable hydrogel for ADSCs encapsulation and RA treatment is proposed. The hydrogel with dendritic polylysine and polysaccharide components is formed through the reversible Schiff base crosslinking. It possesses self‐healing capability, superior mechanical properties, minimal toxicity, and immunomodulatory ability. When encapsulated with ADSCs, the hydrogel could recover chronic inflammation by directly reversing the dominant macrophage phenotype from M1 to M2 and inhibiting the migration of fibroblast‐like synoviocytes. Through a collagen‐induced arthritis rat model, the tremendous therapeutic outcomes of this ADSCs‐laden hydrogel, including inflammation attenuation, cartilage protection, and bone mineral density promotion are demonstrated. These results make the ECM‐inspired hydrogel laden with ADSCs an ideal candidate for treating RA and other autoimmune disorders.