Adipose-Derived Stem-Cell-Derived Exosomes Encapsulated Patch for Modulating Inflammation and Promoting Tissue Regeneration
Yinghua Tao, Tao Liu, Fengya Jing, Xin Tan, Xiaocong Zhao, Katrien V. Bernaerts, Ruipeng Jia, Jun Zhao, Yi Yin, Tianzhu Zhang
Abstract
Repairing tissue, especially in chronic wounds, is a major clinical challenge. Traditional treatments often lead to slow recovery and poor biocompatibility. Adipose-derived stem cell exosomes (ADSC-exo) offer a promising solution for tissue regeneration due to their anti-inflammatory and immunomodulatory effects. However, directly injecting stem cells results in a low survival and function loss. This study introduces a Janus G-Avs patch that promotes tissue repair by releasing ADSC-exo and prevents postoperative tissue adhesion. The patch's top layer, created via coaxial electrospinning, acts as an ADSC-exo delivery system with a core-shell structure by incorporating ADSC-exo and hyaluronic acid (HA) into methacrylate gelatin (GelMA) to prolong exosome release. The bottom layer consists of a 4arm-PLGA(4aPLGA)-Glu/PCL electrospun membrane, offering a lubricated antifouling surface that prevents protein adsorption and provides mechanical support. In rat models, the G-Avs patch has demonstrated its ability to enhance cell proliferation, promote angiogenesis, and encourage macrophage polarization toward the M2 phenotype, thereby mitigating inflammatory responses and promoting tissue repair. Transcriptomic analysis indicates that the G-Avs patch augments cellular energy metabolism by upregulating metabolic pathways and downregulating immune-inflammatory pathways, collectively supporting tissue repair. In summary, the Janus G-Avs patch has a strong clinical potential.