Extracellular Adipose Matrix Hydrogel Laden with Adipose-Derived Stem Cell Modulates Macrophage Polarization for Enhanced Full-Thickness Skin Wound Repair.

Adipose-derived stem cells (ADSC) represent a promising approach for wound healing, while the limited survival rate has restricted their application. To address this, we equipped a hydrogel from acellular porcine adipose tissue (HAPA) with ADSC to fabricate the HAPA + ADSC composite hydrogel. In addition to serving as a carrier for stem cell delivery, the bioactive components of the HAPA hydrogel support immune regulation and tissue repair. In this study, we demonstrated that the HAPA + ADSC composite could effectively modulate macrophage polarization, promote angiogenesis, and regulate extracellular matrix (ECM) deposition and remodeling, thereby substantially accelerating wound healing. Additionally, transcriptomic sequencing analysis indicated that the HAPA + ADSC composite upregulated Nfkbia and Nfkbie to inhibit the nuclear transcription of RelA-p50 heterodimer so that macrophages polarization toward an M1 phenotype is suppressed. The combined effects of ADSC and HAPA hydrogel make it a promising candidate for functional skin wound healing.