Glutaraldehyde-induced porcine model mimics human chronic wounds: insights into pathophysiology and therapeutic applications.

Chronic wounds present a significant clinical challenge due to their complex pathophysiology and resistance to standard treatments. A key obstacle in developing therapies is the lack of animal models that accurately mimic human chronic wound characteristics. Existing rodent models fail to replicate critical features, such as delayed re-epithelialization and unresolved inflammation, while larger animals, including porcine models, also fall short. Here, we introduce a novel glutaraldehyde-induced porcine model that mimics key aspects of human chronic wounds. Glutaraldehyde causes dermal toxicity, resulting in impaired structural integrity, oxidative stress, persistent inflammation, and bacterial colonization. Analyses showed features such as delayed healing, extracellular matrix (ECM) disruption, mitochondrial dysfunction, and chronic inflammatory responses. Comparative transcriptomic and lipidomic studies revealed shared signaling pathways and metabolite profiles with human venous leg and diabetic foot ulcers, highlighting the translational relevance of the model. This innovative platform offers valuable insights into chronic wound mechanisms and aids the development of effective targeted therapies.