Wound Fluid Extracellular Microvesicles: A Potential Innovative Biomarker for Wound Healing

Background: Extracellular vesicles, or microvesicles, are a large family of membrane-bound fluid-filled sacs that cells release into the extracellular environment. Extracellular microvesicles (EMVs) are essential for cell-to-cell communications that promote wound healing. We hypothesize a correlation between the concentration of EMVs in wound fluid and the percentage of wound healing in treated chronic, nonhealing, wounds. A prospective, multicenter, randomized, single-blind clinical trial was conducted to evaluate EMV concentration in relation to wound healing percentages. Methods: Wound fluid samples were obtained from 16 patients with stage IV trunk pressure ulcers. Patients were divided equally into two groups: (1) control group on negative pressure wound therapy (NPWT) alone and (2) study group with NPWT plus porcine extracellular matrix dressing. NPWT was replaced two times a week, and porcine extracellular matrix applied once weekly for all subjects. An NPWT canister device, called a wound vacuum-assisted closure, containing wound fluid was collected from each patient every 4 weeks. EMVs were isolated and the concentration measured by nanoparticle tracking analysis. Results: The study group's total healing percentage was around 89% after 12 weeks compared with the control group's percentage of about 52% (P <= 0.05). Using R programming software, simple linear regression was carried out to investigate the hypothesis. Data demonstrated significant positive correlation (R2 = 0.70; P = 0.05) between EMV concentrations and the healing percentage. Conclusions: There is a positive correlation between EMV concentration and wound healing percentages. Results propose that the EMVs in wound fluid could serve as a biomarker for healing.