Search

Chronic wounds account for 3% of total healthcare expenditure of developed countries; thus, innovative therapies, including Mesenchymal Stem Cells (MSCs) end their exosomes are increasingly considered, even if the activity depends on the whole secretome, made of both soluble proteins and extracellular vesicles. In this work, we prove for the first time the in vivo activity of the whole secretome formulated in a sponge-like alginate wound dressing to obtain the controlled release of bioactive substances. The product has been prepared in a public GMP-compliant facility by a scalable process; based on the murine model, treated wounds healed faster than controls without complications or infections. The treatment induced a higher acute inflammatory process in a short time and sustained the proliferative phase by accelerating fibroblast migration, granulation tissue formation, neovascularization and collagen deposition. The efficacy was substantially supported by the agreement between histological and proteomic findings. In addition to functional modules related to proteolysis, complement and coagulation cascades, protein folding and ECM remodeling, in treated skin, emerged the role of specific wound healing related proteins, including Tenascin (Tnc), Decorin (Dcn) and Epidermal growth factor receptor (EGFR). Of note, Decorin and Tenascin were also components of secretome, and network analysis suggests a potential role in regulating EGFR. Although further experiments will be necessary to characterize better the molecular keys induced by treatment, overall, our results confirm the whole secretome efficacy as novel "cell-free therapy". Also, sponge-like topical dressing containing the whole secretome, GMP- compliant and "ready-off-the-shelf", may represent a relevant point to facilitate its translation into the clinic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [M.L.T., S.P. and M.S. are co-founders and members of the advisory board of the company PharmaExceed S.r.L.]., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Silver sulfadiazine has been frequently used as an antibacterial agent for topical treatment of partial thickness burn wounds. In this study, we present the preparation of silver sulfadiazine microsponges by w/o/w emulsion solvent evaporation method. Formulation variables were optimized by using 3 2 factorial design. The optimized microsponges were characterized by FTIR, DSC, PXRD, particle size analysis, SEM analysis and mercury intrusion porosimetry studies. Viscosity, texture analysis and ex vivo drug deposition study of optimized microsponge loaded gel were also evaluated. The safety of the optimized gel was assessed by MTT assay using epidermal keratinocyte (HaCaT) and mouse embryonic fibroblast (NIH-3T3) cell lines. In vitro antibacterial studies were carried out to compare the antibacterial inhibitory efficiency of the optimized gel against the commercial product. The efficacy of the optimized gel was evaluated by the partial thickness (second degree) burn wound model in mice. Optimized microsponge loaded gel enhanced the drug retaining capacity in the skin layers, by 3 fold higher to that of a commercial product. The antibacterial inhibitory efficiency of optimized gel was similar to the commercial product against the Staphylococcus aureus and Pseudomonas aeruginosa. Optimized gel showed reduced frequency of application, no skin irritation, low cytotoxicity on dermal cell lines and enhanced wound contraction., (Copyright © 2016 Elsevier B.V. All rights reserved.)