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.

Development of biomedical hydrogels for rheumatoid arthritis treatment

“…Hydrogel scaffolds can be used as drug delivery vehicles and also to carry bifunctional molecules to develop a variety of approaches for RA treatment [ 20 , 100 ]. Some recent approaches are described in this section.…”

“…The RA treatment requires preventing discomfort and inflammation, recovering the synovial fluids [ 16 , 17 ], and slowing down the autoimmune-driven gradual damage in joints [ 18 , 19 ]. Hydrogels may exhibit mechanical biomimicry of synovial fluids to protect the joints [20] to sustain normal functioning of joints. In this context, the last decade has witnessed numerous advancements in biomedical materials and polymer technology, and multiple studies have demonstrated the potential application of biomedical hydrogels in RA treatment.…”

The engineering and application of extracellular matrix hydrogels: a review

“…49 Firstly, it can be analyzed through images macroscopically, for which researchers usually use H&E or DAPI staining to check whether the overall decellularization is complete; 50 microscopically, the internal microstructure of the ECM is usually observed by scanning electron microscopy (SEM). 51 One is the breakdown of the protein monomers that make up the ECM matrix. The second is to control the external environment to spontaneously reorganize the intramolecular bonds of the monomeric components into homogeneous gels.…”

A large‐scale production of mesenchymal stem cells and their exosomes for an efficient treatment against lung inflammation

“…Cellular therapy using stem cells, such as MSCs, has shown attractive capabilities of inherent inflammation-guided migration and inflammatory modulation, making them as promising biological agents to treat diverse inflammatory diseases, such as lung inflammation, rheumatoid arthritis and pancreatitis. [1][2][3] Previous studies have indicated that MSCs possessed a unique capability of spontaneous migration to inflammatory sites due to the inherent expression of homingrelated receptors. For example, the expression of CXCR4 on MSCs was believed to be responsible for the inflammation-guided migration owing to their corresponding with the cytokines such as SDF-1α.…”