Human Fibroblast-Derived Matrix Hydrogel Accelerates Regenerative Wound Remodeling Through Interactions With Macrophages
March 2024
in “
Advanced science
”
human fibroblast-derived matrix extracellular matrix hydrogel FDM-gel collagen hydrogel hair follicle formation β-catenin pro-inflammatory cytokines M2-like macrophages VEGF bFGF integrins α5β1 integrins α1β1 Akt phosphorylation matrix metalloproteinase-9 collagen gel hair follicle beta-catenin vascular endothelial growth factor basic fibroblast growth factor integrins MMP-9
TLDR A new hydrogel made from human cells improves wound healing by working with immune cells to promote repair.
The study introduces a novel extracellular matrix (ECM) hydrogel made from human fibroblast-derived matrix (FDM) that shows promise in enhancing wound healing. The FDM-gel is stable, viscoelastic, and maintains natural ECM components and bioactive factors. When applied to full-thickness wounds, the FDM-gel outperformed collagen hydrogel, particularly in hair follicle formation, by upregulating β-catenin. It also reduced pro-inflammatory cytokines and increased M2-like macrophages, VEGF, and bFGF levels. The healing effects are partly due to interactions between macrophages and the FDM-gel via integrins α5β1 and α1β1, which boost VEGF and bFGF production, Akt phosphorylation, and matrix metalloproteinase-9 activity. Blocking these interactions reduced the secretion of healing factors, and depleting macrophages in an animal model lessened the gel's effectiveness. The FDM-gel thus acts as an immunomodulatory material that supports cell infiltration and regenerative matrix remodeling for improved wound healing.