Human Fibroblast-Derived Matrix Hydrogel Accelerates Regenerative Wound Remodeling Through the Interactions with...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• The extracellular matrix (ECM) plays a crucial role in tissue repair and regeneration.
• Developing advanced wound healing materials requires preserving native ECM bioactivity.
• Current treatments often lack the necessary complexity to fully support regenerative processes.

Purpose of the Study:

• To develop and evaluate a novel hydrogel derived solely from decellularized human fibroblast-derived matrix (FDM) for advanced wound healing.
• To investigate the immunomodulatory properties and regenerative potential of the FDM-gel.
• To elucidate the mechanisms underlying FDM-gel's efficacy in promoting wound repair.

Main Methods:

• Fabrication of a stable, viscoelastic hydrogel from decellularized human fibroblast-derived matrix (FDM).
• In vivo assessment of FDM-gel in full-thickness wound models, comparing it to collagen hydrogel.
• Analysis of immune cell infiltration, cytokine profiles, growth factor expression (VEGF, bFGF), and molecular signaling pathways (β-catenin, Akt, MMP-9).
• Investigation of macrophage-FDM interactions using integrin inhibitors and macrophage depletion models.

Main Results:

• FDM-gel demonstrated superior wound healing compared to collagen hydrogel, notably promoting hair follicle formation.
• The hydrogel facilitated innate immune cell infiltration and modulated macrophage polarization towards an M2-like phenotype.
• FDM-gel significantly increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels.
• Macrophage interaction with FDM-gel via integrins α5β1 and α1β1 was critical for growth factor production and pro-healing signaling.

Conclusions:

• FDM-gel is a promising biomaterial for advanced wound healing due to its physical stability and preserved bioactivity.
• The hydrogel acts as an immunomodulatory agent, promoting a pro-regenerative environment.
• Macrophage-mediated interactions with FDM-gel are essential for its therapeutic effects, driving matrix remodeling and complete wound closure.