Large skeletal muscle defects due to trauma or following tumor extirpation can result in substantial functional impairment. Purified exosomes are now available clinically and have been used for wound healing. The objective of this study was to evaluate the regenerative capacity of commercially available exosomes on an animal model of volumetric muscle loss (VML) and potential translation to human muscle injury. An established VML rat model was used. In the in-vitro experiment, rat myoblasts were isolated and co-cultured with 5% purified exosome product (PEP) to validate uptake. Myoblast proliferation and migration was evaluated with increasing concentrations of PEP (2.5%, 5%, and 10%) in comparison to control media(F10) and myoblast growth media (MGM). In the in-vivo experiment, a lateral gastrocnemius-VML defect was made in the rat hindlimb. Animals were randomized into four experimental groups; defects were treated with either surgery alone, fibrin sealant, fibrin sealant and PEP, or platelet rich plasma (PRP). The groups were further randomized into four recovery timepoints (14, 28, 45, or 90 days). The isometric tetanic force (ITF), which was measured as a percentage of force compared to normal limb, was used for functional evaluation. Florescence microscopy confirmed that 5% PEP demonstrated cellular uptake around 8-12 hrs. Compared to control, myoblasts showed faster proliferation with PEP irrespective of concentration. PEP concentrations of 2.5 and 5% promoted myoblast migration faster compared to control (<0.05). At 90 days postop, both the PEP and fibrin sealant and PRP groups showed greater ITF compared to control and fibrin sealant alone (<0.05). At 45 days postop, PEP with fibrin sealant had greater cellularity compared to control (<0.05). At 90 days postop, both PEP with fibrin sealant and the PRP treated groups had greater cellularity compared to fibrin sealant and control (<0.05). PEP promoted myoblast proliferation and migration. When delivered to a wound with a fibrin sealant, PEP allowed for muscle regeneration producing greater functional recovery and more cellularity in vivo compared to untreated animals. PEP may promote muscle regeneration in cases of VML, further research is warranted to evaluate PEP for the treatment of clinical muscle defects.

Cortex Moutan is the root bark of the buttercup plant Paeonia suffruticosa Andr, of Ranunculaceae family. It has been utilized in Chinese medicine for thousands of years to treat a multitude of diseases, and traditional Chinese documents allege that it has heat-clearing, antipyretic, anti-inflammatory and detoxicating properties. Paeonol is a bioactive substance extracted from Cortex Moutan, which is considered to be one of its most effective metabolites. Recent studies have illustrated that paeonol treatment can alleviate skin damage, relieve the inflammatory response in patients with numerous dermatological conditions, and inhibit anomalous proliferation of skin tissue. Accordingly, paeonol may serve as a potential therapeutic agent for a variety of skin conditions. This review summarizes the physicochemical properties and pharmacokinetics (PK) characteristics of paeonol, and mechanisms of operation in diverse skin diseases, including dermatitis, psoriasis, pruritus, photoaging, hyperpigmentation, and hyperplasticscar. Additionally, much of the evidence is based on animal experiments. Furthermore, it explores the prospects of enhancing paeonol’s efficacy through extraction, synthesis, and formulation innovations, as well as strategies to overcome its limitations in dermatological therapy. This review aims to provide a more reliable theoretical basis for the clinical application of paeonol.

Background. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) possess similar proregenerative effects when injected into defects immediately following trauma. However, MSC-EVs are superior to MSCs in terms of storage and rejection reflection, while immediate administration of MSC-EVs is related to several target cells for most donor cells die within few weeks. Besides, the inflammatory cascade is incited, providing an unfavorable environment for target cells. We hypothesized that delayed injection of MSC-EVs might have priority on tissue regeneration than instant injection. Method. Extracellular vesicles isolated from adipose-derived mesenchymal stromal cells (ADSC-EVs) were administered into human umbilical vein endothelial cells (HUVECs) in vitro at different doses. The migration of HUVECs was assessed using the scratch wound healing assay, whereas the length of tubes and number of vessel-like structures formed by HUVECs were determined using tube formation assay. Next, 24 BALB/c nude mice were randomly divided into three groups ( ). For the EV-delayed group, ADSC-EVs were injected into transplanted fat a week later than the EV-immediate group. The volume and weight of grafts were measured at 3 months after fat transplantation. Further, the number of CD31-possitive vessels and CD206-possitive cells in the fat grafts was quantified. Results. Compared with the EV-immediate group, the EV-delayed group had a higher fat tissue retention volume ( mL versus mL), more neovessels ( versus ), and fewer cysts. Furthermore, there were more Ki67-positive cells ( versus ) and CD206-positive M2 macrophages cells ( versus ) in the EV-delayed group than in the EV-immediate group. Conclusion. Delayed injection of ADSC-EVs promotes fat graft volume retention by stimulating angiogenesis. These findings suggest that delayed supplementation might be a more effective strategy for the application of MSC-EVs in tissue regeneration.