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Chronic wounds have a large impact on health, affecting ∼6.5 M people and costing ∼$25B/year in the US alone. We previously discovered that a genetically modified mouse model displays impaired healing similar to problematic wounds in humans and that sometimes the wounds become chronic. Here we show how and why these impaired wounds become chronic, describe a way whereby we can drive impaired wounds to chronicity at will and propose that the same processes are involved in chronic wound development in humans. We hypothesize that exacerbated levels of oxidative stress are critical for initiation of chronicity. We show that, very early after injury, wounds with impaired healing contain elevated levels of reactive oxygen and nitrogen species and, much like in humans, these levels increase with age. Moreover, the activity of anti-oxidant enzymes is not elevated, leading to buildup of oxidative stress in the wound environment. To induce chronicity, we exacerbated the redox imbalance by further inhibiting the antioxidant enzymes and by infecting the wounds with biofilm-forming bacteria isolated from the chronic wounds that developed naturally in these mice. These wounds do not re-epithelialize, the granulation tissue lacks vascularization and interstitial collagen fibers, they contain an antibiotic-resistant mixed bioflora with biofilm-forming capacity, and they stay open for several weeks. These findings are highly significant because they show for the first time that chronic wounds can be generated in an animal model effectively and consistently. The availability of such a model will significantly propel the field forward because it can be used to develop strategies to regain redox balance that may result in inhibition of biofilm formation and result in restoration of healthy wound tissue. Furthermore, the model can lead to the understanding of other fundamental mechanisms of chronic wound development that can potentially lead to novel therapies.

The involvement of microorganisms in low-density polyethylene (LDPE) degradation is widely studied across the globe. Even though soil, landfills, and garbage dumps are reported to be promising niches for such organisms, recently the involvement of wood decay fungi in polyethylene degradation is highlighted. In light of this, 50 fungal samples isolated from decaying hardwoods were assessed for their wood degradation ability and for their depolymerization enzymatic activities. For the LDPE deterioration assay, 22 fungal isolates having wood decay ability and de-polymerization enzymatic activities were selected. Fungal cultures with LDPE sheets (2 cm x 10 cm x 37.5 μm) were incubated in the presence and in the absence of wood as the carbon source (C) for 45 days. Degradation was measured by weight loss, changes in tensile properties, reduction in contact angle, changes of functional groups in Fourier-transform infrared spectroscopy, Scanning electron microscopic imaging, and CO2 evolution by strum test. Among the isolates incubated in the absence of wood, Phlebiopsis flavidoalba out-performed the other fungal species showing the highest percentage of weight reduction (23.68 ± 0.34%), and the lowest contact angle (64.28° ± 5.01). Biodegradation of LDPE by P. flavidoalba was further supported by 46.79 ± 0.67% of the mass loss, and 3.07 ± 0.13% of CO2 emission (mg/L) in the strum test. The most striking feature of the experiment was that all the isolates showed elevated degradation of LDPE in the absence of wood than that in the presence of wood. It is clear that in the absence of a preferred C source, wood decay fungi thrive to utilize any available C source (LDPE in this case) showing the metabolic adaptability of fungi to survive under stressful conditions. A potential mechanism for LDPE degradation is also proposed., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Perera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)