No abstract

Unhealable diabetic wounds need to be addressed with the help of newer, more efficacious strategies. Exosomes combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound treatment. Here, the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch (SFP) were demonstrated to promote diabetic wound healing. Silk fibroin binding peptide (SFBP) was screened through phage display, and SFBP-Gluc-MS2 (SGM) and pac-miR146a-pac fusion protein were constructed. The designed exosomes (SGM-Exos, miR146a-Exos, and SGM-miR146a-Exos) were isolated from the engineered placental mesenchymal stem cells (PMSCs) transduced with SGM or/and pac-miR146a-pac protein. Gluc signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of SGM-Exo. Moreover, the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in miR146a-Exos. Superior to untreated, SGM-miR146a-Exo-only treated, and SFP-only treated groups, SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation, collagen deposition, and neovascularization. The transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP treatment. Here, we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

The application of photobiomodulation (PBM) in regenerative medicine has expanded to the treatment of alopecia caused by various reasons. However, the mechanisms responsible for its effects are poorly understood. Here, we aimed to investigate the effects of PBM on hair regeneration in injured skin and to explore the underlying mechanisms. The scratched epidermis or dermis models were established in C57 mice aged 7–8 weeks. We found that the scratched epidermis had no influence on hair regeneration, but the scratched dermis led to obvious hair follicle atrophy and significantly influenced hair regeneration. The wounds in scratched dermis models were treated with PBM (655 nm, 3 J/cm2 [10 min]) and the hair regeneration and cell proliferation in hair follicle were evaluated. Compared with control, the hair coverage level was significantly enhanced after PBM treatment. Sox9+ and PCNA+ cells in hair follicle were obviously observed in PBM‐treated group, but not in control. In vitro, the effects of PBM on the function of dermal papilla cells (DPCs) were investigated. The results showed that the migration of DPCs was increased significantly by PBM (655 nm, 3 J/cm2 [10 min]), whereas no effect was found on proliferation. Furthermore, we found that PBM promoted exosome secretion of DPCs, accompanied by the activation of Akt/GSK‐3β/β‐catenin pathway. AKT inhibitor MK‐2206 effectively blocked PBM‐induced migration and exosome secretion of DPCs. These findings suggest that the enhanced migration and exosome secretion of DPCs mediated by the Akt/GSK‐3β/β‐catenin pathway were responsible for the promotion of hair regeneration in injured skin by PBM.

Chronic non-healing wounds have posed a severe threat to patients mentally and physically. Behavior dysregulation of remaining cells at wound sites is recognized as the chief culprit to destroy healing process and hinders wound healing. Therefore, regulating and restoring normal cellular behavior is the core of chronic non-healing wound treatment. In recent years, the therapy with mesenchymal stem cells (MSCs) has become a promising option for chronic wound healing and the efficacy has increasingly been attributed to their exocrine functions. Small extracellular vesicles derived from MSCs (MSC-sEVs) are reported to benefit almost all stages of wound healing by regulating the cellular behavior to participate in the process of inflammatory response, angiogenesis, re-epithelization, and scarless healing. Here, we describe the characteristics of MSC-sEVs and discuss their therapeutic potential in chronic wound treatment. Additionally, we also provide an overview of the application avenues of MSC-sEVs in wound treatment. Finally, we summarize strategies for large-scale production and engineering of MSC-sEVs. This review may possibly provide meaningful guidance for chronic wound treatment with MSC-sEVs.