In this study, methacrylamide chitosan modified with perfluorocarbon chains (MACF) is used as the base material to construct hydrogel dressings for treating dermal wounds. MACF hydrogels saturated with oxygen (+ O2) are examined for their ability to deliver and sustain oxygen, degrade in a biological environment, and promote wound healing in an animal model. The emerging technique of metabolomics is used to understand how MACF + O2 hydrogel dressings improve wound healing. Results indicate that MACF treatment facilitates oxygen transport rate that is two orders of magnitude greater than base MAC hydrogels. MACF hydrogel dressings are next tested in an in vivo splinted rat excisional wound healing model. Histological analysis reveals that MACF + O2 dressings improve re-epithelialization (p < 0.0001) and synthesis of collagen over controls (p < 0.01). Analysis of endogenous metabolites in the wounds using global metabolomics demonstrates that MACF + O2 dressings promotes a regenerative metabolic process directed toward hydroxyproline and collagen synthesis, with confirmation of metabolite levels within this pathway. The results of this study confirm that increased oxygen delivery through the application of MACF + O2 hydrogels enhances wound healing and metabolomics analyses provides a powerful tool to assess wound healing physiology.
Amniotic tissues have been long utilised to treat chronic wounds; however, there are few studies evaluating how the wound microenvironment responds to these therapies. The goal of this study was to evaluate the changes in wounds treated with a hypothermically stored amniotic membrane (HSAM). In this prospective single‐arm study, 15 female patients with venous leg ulcers were treated with HSAM from male donors and standard of care for 12 weeks. Over the course of the study, wound exudate was collected and evaluated using proteomic microarrays. Biopsies were collected during the course of treatment to detect the presence of HSAM tissue. By 4 weeks, 60% of subjects achieved 50% or greater reduction in wound size, and by 12 weeks, 53% of subjects achieved 100% re‐epithelialization. HSAM DNA was detected in 20% of biopsies as determined by the detection TSPY4, indicating HSAM was no longer present within the wound bed approximately 7 days from the last treatment for the majority of wounds. Proteomic analysis of wound exudate found that wounds on a healing trajectory had significantly higher levels of MMP‐10, MMP‐7, and TIMP‐4 and significantly lower levels of CX3CL1, FLT‐3 L, IL‐1ra, IL‐1a, IL‐9, IL‐2, IL‐3, MCP‐1, and TNF‐b compared with other wounds.
Forty-one adolescent males (11.1-18.3 yr) with cystic fibrosis (CF) and 37 healthy adolescent males (11.1-17.9 yr) performed a Wingate Anaerobic Test (WAnT). The group with CF was subdivided by sexual maturity, nutritional status, and degree of airway obstruction. The subjects with CF had lower absolute power outputs than the healthy controls [mean power in Watts (mean +/- SD): 350.2 +/- 135.9 vs 424.5 +/- 120.4, P < 0.001; peak power: 525.2 +/- 178.4 vs 665.9 +/- 191.3, P < 0.001). When absolute power was corrected for lean body mass, the subjects with CF had lower power outputs than the healthy controls (mean power in W.kg-1: 8.9 +/- 1.7 vs 9.6 +/- 0.9, P < 0.05; peak power: 13.4 +/- 2.1 vs 15.0 +/- 1.6, P < 0.05). The subgroup with CF with a higher body mass index (BMI > 17.5 kg.m-2) had higher peak and mean power output than subjects with CF with a lower BMI in both absolute power and when power was expressed per lean body mass. When sexual maturation was considered, subjects with CF with salivary testosterone greater than 4.0 ng.dl-1 had a higher mean and peak power in both absolute terms and relative to lean body mass than subjects with CF with salivary testosterone less than 4.0 ng.dl-1. Multiple regression analysis indicated that the nutritional factor accounted for 70%-80% of the variability in power output in the subjects with CF, while testosterone accounted for 10% of the variability. Pulmonary function was not a significant independent correlate of anaerobic power. Our results suggest that nutritional status, and to a lesser extent maturational factors, may play a more important role than pulmonary function in determining anaerobic fitness in male adolescents with CF.
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