Adipose-Derived Stem Cell-Loaded Fish-GelMA/CMC Hydrogel Accelerates Wound Healing via Macrophage Polarization Suppression and Promoting Angiogenesis.

Abstract

Extensive cutaneous injuries with impaired regenerative capacity present substantial risks to both public health and socioeconomic systems. Current skin substitutes remain inadequate in fully replicating native tissue architecture and physiological functionality. While fish skin-derived gelatin-methacrylate (F-GelMA) serves as a principal scaffold material in vitro skin models, it has weak mechanical properties and limited mechanical strength, which necessitates supplementation with viscosity-enhancing additives. We created functional in vitro 3D extracellular matrix mimics with composite hydrogels based on F-GelMA and the thickener carboxymethyl cellulose (CMC). The physicochemical properties and bioactivity of the hydrogel scaffolds were assessed through testing their rheological properties, swelling behavior, degradation characteristics, and biocompatibility. It was discovered that the F-GelMA/CMC hydrogel bioscaffold loaded with adipose-derived stem cells (ADSCs) expedited wound healing by facilitating wound re-epithelialization, enhancing wound collagen formation, accelerating the deposition of myofibroblasts at the wound site, promoting angiogenesis, stimulating the proliferation and differentiation of keratinocytes, and suppressing skin wound inflammation.