Human Adipose-derived Mesenchymal Stem Cells-Derived Exosomes Encapsulated in Pluronic F127 Hydrogel Promote Wound Healing and Regeneration

Abstract Background: Large area skin trauma has always been a great challenge for both patients and clinicians. Exosomes originated from human adipose-derived mesenchymal stem cells (hADSCs) have been a novel promising cell-free treatment in cutaneous damage repair. Nevertheless, the low retention rate of exosomes post-transplantation in vivo remains a significant challenge in clinical applications. Herein, we purposed to explore the potential clinical application roles of hADSCs-Exos encapsulated in functional PF-127 hydrogel in wound healing.Methods: hADSCs-Exos were isolated from human hADSCs by ultracentrifugation. An injectable, biocompatible, and thermo-sensitive hydrogel Pluronic F-127 hydrogel was employed to encapsulate allogeneic hADSCs-Exos, and this complex was topically applied to a full-thickness cutaneous wound in mice. On different days post-transplantation, the mice were sacrificed, and the skin tissue was excised for histological and immunohistochemical analysis.Results: PF-127/hADSCs-Exos complex enhanced skin wound healing, promoted re-epithelialization, increased expression of Ki67, α-SMA, and CD31, facilitated collagen synthesis (Collagen I, Collagen III), reduced inflammation (IL-6, TNF-α, CD68, CD206), and up-regulated expression of skin barrier proteins (KRT1, AQP3). The results showed that both PF-127/hADSCs-Exos and hADSCs-Exos could improve the cwound healing process at a similar level.Conclusion: PF-127/hADSCs-Exos combination can maintain the bioactivity of hADSCs-Exos and control the exosome release. The low-frequency administration of PF-127/hADSCs-Exos could promote cutaneous wound healing instead of the high-frequency administration of pure exosomes. Thus, this biomaterial-based exosome will be a promising treatment approach for the cutaneous rejuvenation of skin wounds.