Crosslinked Collagen‐Hyaluronic Acid Scaffold Enhances Interleukin‐10 Under Co‐Culture of Macrophages And Adipose‐Derived Stem Cells

Abstract The skin, the human body's largest organ, possesses a protective barrier that renders it susceptible to various injuries, including burns. Following burn trauma, the inflammatory process triggers both innate and adaptive immune responses, leading to the polarization of macrophages into two distinct phenotypes: the pro‐inflammatory M1 and the anti‐inflammatory M2. This dual response sets the stage for wound healing and subsequent tissue regeneration. Contributing to this transition from M1 to M2 polarization are human adipose‐derived stem cells (ASCs), which employ paracrine signaling and inflammation suppression to enhance the remodeling phase. ASCs, when combined with biocompatible polymers, can be integrated into functional scaffolds. This study introduces an 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide‐crosslinked (EDC‐crosslinked) collagen‐hyaluronic acid (Col‐HA) scaffold assembled with ASCs, designed as a natural biomaterial device to modulate macrophage behavior in vitro under co‐culture conditions. This innovation aims to improve wound healing processes. The EDC‐crosslinked Col‐HA scaffold favored the release of anti‐inflammatory cytokines by ASCs, which indicated the M2 prevalence. In tissue engineering, a critical objective lies in the development of functional biomaterials capable of guiding specific tissue responses, notably the control of inflammatory processes. Thus, this research not only presents original findings but also points toward a promising avenue within regenerative medicine.