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Abstract:The refractory diabetic wound has remained a worldwide challenge as one of the major health problems. The impaired angiogenesis phase during diabetic wound healing partly contributes to the pathological process. MicroRNA (miRNA) is an essential regulator of gene expression in crucial biological processes and is a promising nucleic acid drug in therapeutic fields of the diabetic wound. However, miRNA therapies have limitations due to lacking an effective delivery system. In the present study, we found a significant reduction of miR-31-5p expression in the full-thickness wounds of diabetic mice compared to normal mice. Further, miR-31-5p has been proven to promote the proliferation, migration, and angiogenesis of endothelial cells. Thus, we conceived the idea of exogenously supplementing miR-31-5p mimics to treat the diabetic wound. We used milk-derived exosomes as a novel system for miR-31-5p delivery and successfully encapsulated miR-31-5p mimics into milk exosomes through electroporation. Then, we proved that the miR-31-5p loaded in exosomes achieved higher cell uptake and was able to resist degradation. Moreover, our miRNA-exosomal formulation demonstrated dramatically improved endothelial cell functions in vitro, together with the promotion of angiogenesis and enhanced diabetic wound healing in vivo. Collectively, our data showed the feasibility of milk exosomes as a scalable, biocompatible, and cost-effective delivery system to enhance the bioavailability and efficacy of miRNAs.

KEYWORDS:Milk-derived exosomesmiR-31-5pdrug deliverydiabetic woundangiogenesis

Abstract: Wounds are among the most common skin conditions, displaying a large etiological diversity and being characterized by difffferent degrees of severity. Wound healing is a complex process that involves multiple steps such as inflflammation, proliferation and maturation and ends with scar formation. Since ancient times, a widely used option for treating skin wounds are plantbased treatments which currently have become the subject of modern pharmaceutical formulations. Triterpenes with tetracyclic and pentacyclic structure are extensively studied for their implication in wound healing as well as to determine their molecular mechanisms of action. The current review aims to summarize the main results of in vitro, in vivo and clinical studies conducted on lupane, ursane, oleanane, dammarane, lanostane and cycloartane type triterpenes as potential wound healing treatments.

Keywords: wound healing; pentacyclic triterpenes; tetracyclic triterpenes

Abstract: Mangifera indica can generate up to 60% of polluting by-products, including peels. However,it has been shown that flflavonoids and mangiferin are mainly responsible for the antioxidant, antiinflflammatory, and antibacterial activities closely related to the wound-healing process. The chemical composition of MEMI (methanolic extract of M. indica) was analyzed by HPLC-DAD, as well as concentrations of total phenol (TPC) and flflavonoids (TFC) and antioxidant activity (SA50). Wound healing effificacy was determined by measurements of wound contraction, histological analysis, and tensiometric method; moreover, anti-inflflammatory, antibacterial, and acute dermal toxicity (OECD 402) were also evaluated. Phenol, resorcinol, conjugated resorcinol, and mangiferin were detected. TPC, TFC, and SA50 were 136 mg GAE/g, 101.66 mg QE/g, and 36.33 µg/mL, respectively. Tensile strength and wound contraction closure did not show signifificant differences between MEMI and dexpanthenol groups. Histological analysis (after 14 days) shows a similar architecture between MEMI treatment and normal skin. MEMI exhibits a reduction in edema. Staphylococcus epidermidis had an MIC of 2 mg/mL, while Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli reached 4 mg/mL. The MEMI showed no signs of toxicity. Therefore, this study demonstrates multiple targets that flflavonoids and mangiferin of MEMI may present during the healing process.

Keywords: Mangifera indica peel; wound healing; antibacterial; antioxidant.

Abstract: Honey is a natural product rich in several phenolic compounds, enzymes, and sugars with antioxidant, anticarcinogenic, anti-inflflammatory, and antimicrobial potential. Indeed, the development of honey-based adhesives for wound care and other biomedical applications are topics being widely investigated over the years. Some of the advantages of the use of honey for wound-healing solutions are the acceleration of dermal repair and epithelialization, angiogenesis promotion, immune response promotion and the reduction in healing-related infections with pathogenic microorganisms. This paper reviews the main role of honey on the development of wound-healing-based applications, the main compounds responsible for the healing capacity, how the honey origin can inflfluence the healing properties, also highlighting promising results in in vitro and in vivo trials. The challenges in the use of honey for wound healing are also covered and discussed. The delivery methodology (direct application, incorporated in fifibrous membranes and hydrogels) is also presented and discussed.

Keywords: honey; wound-healing; antioxidant; antimicrobial; hydrogels; dermal repair; hydrogel