Dissolved oxygen technologies as a novel strategy for non-healing wounds: A critical review

Non-healing wounds are steadily becoming a global-health issue. Prolonged hypoxia propagates wound chronicity; yet, oxygenating treatments are considered inadequate to date. Dissolved oxygen (DO) in aqueous solutions introduces a novel approach to enhanced wound oxygenation, and is robustly evaluated for clinical applications. A systematic literature search was conducted, whereby experimental and clinical studies of DO technologies were categorized per engineering approach. Technical principles, methodology, endpoints and outcomes were analysed for both oxygenating and healing effects. Forty articles meeting our inclusion criteria were grouped as follows: DO solutions (17), oxygen (O-2) dressings (9), O-2 hydrogels (11) and O-2 emulsions (3). All technologies improved wound oxygenation, each to a variable degree. They also achieved at least one statistically significant outcome related to wound healing, mainly in epithelialization, angiogenesis and collagen synthesis. Scarcity in clinical data and methodological variability precluded quantitative comparisons among the biotechnologies studied. DO technologies warrantee further evaluation for wound oxygenation in the clinical setting. Standardised methodologies and targeted research questions are pivotal to facilitate global integration in healthcare

Extracellular Vesicles Secreted by Corneal Myofibroblasts Promote Corneal Epithelial Cell Migration

Corneal epithelial wound healing is a multifaceted process that encompasses cell proliferation, migration, and communication from the corneal stroma. Upon corneal injury, bidirectional crosstalk between the epithelium and stroma via extracellular vesicles (EVs) has been reported. However, the mechanisms by which the EVs from human corneal keratocytes (HCKs), fibroblasts (HCFs), and/or myofibroblasts (HCMs) exert their effects on the corneal epithelium remain unclear. In this study, HCK-, HCF-, and HCM-EVs were isolated and characterized, and human corneal epithelial (HCE) cell migration was assessed in a scratch assay following PKH26-labeled HCK-, HCF-, or HCM-EV treatment. HCE cells proliferative and apoptotic activity following EV treatment was assessed. HCF-/HCM-EVs were enriched for CD63, CD81, ITGAV, and THBS1 compared to HCK-EV. All EVs were negative for GM130 and showed minimal differences in biophysical properties. At the proteomic level, we showed HCM-EV with a log >two-fold change in CXCL6, CXCL12, MMP1, and MMP2 expression compared to HCK-/HCF-EVs; these proteins are associated with cellular movement pathways. Upon HCM-EV treatment, HCE cell migration, velocity, and proliferation were significantly increased compared to HCK-/HCF-EVs. This study concludes that the HCM-EV protein cargo influences HCE cell migration and proliferation, and understanding these elements may provide a novel therapeutic avenue for corneal wound healing

Dissolved oxygen technologies as a novel strategy for non-healing wounds: a critical review

Summarization: Non-healing wounds are steadily becoming a global-health issue. Prolonged hypoxia propagates wound chronicity; yet, oxygenating treatments are considered inadequate to date. Dissolved oxygen (DO) in aqueous solutions introduces a novel approach to enhanced wound oxygenation, and is robustly evaluated for clinical applications. A systematic literature search was conducted, whereby experimental and clinical studies of DO technologies were categorized per engineering approach. Technical principles, methodology, endpoints and outcomes were analysed for both oxygenating and healing effects. Forty articles meeting our inclusion criteria were grouped as follows: DO solutions (17), oxygen (O2) dressings (9), O2 hydrogels (11) and O2 emulsions (3). All technologies improved wound oxygenation, each to a variable degree. They also achieved at least one statistically significant outcome related to wound healing, mainly in epithelialization, angiogenesis and collagen synthesis. Scarcity in clinical data and methodological variability precluded quantitative comparisons among the biotechnologies studied. DO technologies warrantee further evaluation for wound oxygenation in the clinical setting. Standardised methodologies and targeted research questions are pivotal to facilitate global integration in healthcare.Presented on

Mesenchymal stromal cell extracellular vesicles improve lung development in mechanically ventilated preterm lambs

Background: Novel therapies are needed for bronchopulmonary dysplasia (BPD) because no effective treatment exists. Mesenchymal stromal cell extracellular vesicles (MSC-sEVs) have therapeutic efficacy in a mouse pup neonatal hyperoxia BPD model. We tested the hypothesis that MSC-sEVs will improve lung functional and structural development in mechanically ventilated preterm lambs. Methods: Preterm lambs (~129d; equivalent to human lung development at ~28w gestation) were exposed to antenatal steroids, surfactant, caffeine citrate, and supported by mechanical ventilation for 6-7d. Lambs were randomized to blinded treatment with either MSC-sEVs (human bone marrow MSC-derived; 2x1011 particles iv; n=8; 4F/4M) or vehicle control (saline iv; 4F/4M). Treatment was at 6 and 78 hours post-delivery. Physiological targets were pulse oximetry O2 saturation 90-94% (PaO2 60-90 mmHg), PaCO2 45-60 mmHg (pH 7.25-7.35), and tidal volume 5-7 mL/Kg. Results: MSC-sEVs-treated preterm lambs tolerated enteral feedings and maintained weight compared to the vehicle control group. Respiratory severity score, oxygenation index, A-a gradient, distal airspace wall thickness, and smooth muscle thickness around terminal bronchioles and pulmonary arterioles were lower (*) for the MSC-sEVs group versus the vehicle controls. S/F ratio, radial alveolar count, secondary septal volume density, alveolar capillary surface density, and protein abundance of VEGF-R2 were higher (*) for the MSC-sEVs versus the vehicle control group. Conclusions: MSC-sEVs improved respiratory system physiology and alveolar formation in mechanically ventilated preterm lambs. MSC-sEVs may be an effective and safe therapy for appropriate functional and structural development of the lung in preterm infants who require mechanical ventilation and are at-risk of developing BPD