Octopus -inspired gelatin-methacrylate scaffolds loaded with hBMSC-derived exosomes promote wound healing by regulating macrophage polarization

Excessive local movement and inflammation are common problems in the process of wound repair, which lead to failure of later repair. In order to solve this problem, inspired by the octopus sucker structure, we successfully developed a photocrosslinked hydrogel that can adsorb skin surface fascia. In addition, extracellular vesicles from human bone marrow mesenchymal stem cells are encapsulated in the octopus like sucker structure. The morphology and structure of extracellular vesicles in bone marrow mesenchymal stem cells were detected by scanning electron microscopy and particle size analysis. Through iTRAQ, we tested the expression of angiogenesis related proteins contained in extracellular vesicles. Design small interfering RNA to verify its impact on angiogenic related genes and proteins. Macrophage polarization was detected by immunofluorescence. The expression of new blood vessels was detected by constructing a skin defect model and injecting microfil contrast agent into the heart. When the sucker is firmly adsorbed on the damaged wound, the sucker will slowly degrade. Using its delivery system, it is observed that the extracellular vesicles are released in the wound. Through iTRAQ, it was found that the angiogenesis regulator (angiopoietin-like 4, angiopoietin-like 3 and aminopeptidase N) released in the extracellular vesicles regulates collagen deposition, angiogenesis, and inhibits macrophage aggregation. In addition, the slowly released extracellular vesicles will further inhibit the polarization of proinflammatory macrophages. This biological behavior can provide an adaptive microenvironment for skin regeneration at an early stage. This new bionic octopus sucker structure gel creates a good microenvironment for wound repair and shortens the wound healing time. Therefore, this hydrogel inspired by the octopus sucker structure may provide a good strategy and commercial value for promoting wound repair treatment in clinical practice.