Light-activated extracellular matrix microcarriers with engineered MSCs loading for autoimmune psoriasis treatment

The stem-cell-therapy supported by hydrogel microcarriers has shown potentials in the regulation of autoimmune diseases. Trends in this field focus on enhancing the viability and the delivery controllability of stem cells. Herein, we proposed novel fish extracellular matrix (ECM) microcarriers loaded with mesenchymal stem cells (MSCs) that secrete programmed cell death-ligand 1 (PD-L1) for autoimmune disease treatment. We developed an optimized acellular method to extract the fish skin ECM, followed by mixing it with ruthenium (Ru)/sodium persulfate (SPS) to generate light-activated ECM bio-ink. By introducing this bio-ink into a droplet microfluidic device, porous ECM microcarriers could be generated after in-situ photocrosslinking. With the decoration of polydopamine, MSCs with enhanced PD-L1 expression by lentivirus transfection can adhere well to these ECM microcarriers, serving as ideal candidate for stem-cell-therapy. We have demonstrated that the engineered MSCs delivered through the ECM microcarriers have a higher survival rate compared with direct injection. Besides, these MSCs-loaded microcarriers can effectively inhibit the epidermis thickening and lower the PASI score in an in vivo psoriasis model. Therefore, the proposed engineered MSCs-loaded ECM microcarriers are anticipated to pave the way for promising clinical treatments of autoimmune psoriasis diseases.