Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity

Abstract

The efficient healing of a skin wound is something that most of us take for granted but is essential for surviving day-to-day knocks and cuts, and is absolutely relied on clinically whenever a patient receives surgical intervention. However, the management of a chronic wound – defined as a barrier defect that has not healed in 3 months – has become a major therapeutic challenge throughout the Western world, and it is a problem that will only escalate with the increasing incidence of conditions that impede wound healing, such as diabetes, obesity and vascular disorders. Despite being clinically and molecularly heterogeneous, all chronic wounds are generally assigned to one of three major clinical categories: leg ulcers, diabetic foot ulcers or pressure ulcers. Although we have gleaned much knowledge about the fundamental cellular and molecular mechanisms that underpin healthy, acute wound healing from various animal models, we have learned much less about chronic wound repair pathology from these models. This might largely be because the animal models being used in this field of research have failed to recapitulate the clinical features of chronic wounds. In this Clinical Puzzle article, we discuss the clinical complexity of chronic wounds and describe the best currently available models for investigating chronic wound pathology. We also assess how such models could be optimised to become more useful tools for uncovering pathological mechanisms and potential therapeutic treatments.

Impaired wound healing: facts and hypotheses for multi-professional considerations in predictive, preventive and personalised medicine

“…Chronic wounds are defined as those which do not follow the normal healing process and show no signs of effective healing within 3 months after the tissue injury [4]. The features characteristic for the chronic wounds are prolonged or excessive inflammatory phase [5], overabundant neutrophil infiltration [6], persistent infections [7], and frequent formation of tissue/organ atypical biofilms [8,9].…”

Pathologic changes of pancreatic endothelial cells in Diabetic Rat

“…Limit of the mitochondria ATP has caused the loss of nucleoside in β-cell and the damage of DNA. Due to the stimulation of STZ, the polymerization of more ADP ribose base happened, further reducing the ATP number and inhibiting the synthesis and secretion of insulin [16][17][18]. These study shows that the pancreatic acinar epithelial cells and islet structure in the diabetes rats damaged and degenerated, islet edge was not neat, and the disordered arrangement of cells appeared.…”

The Role of Myeloid Lineage Cells on Skin Healing and Skin Regeneration

“…In diabetes, 25% of patients develop foot ulcers that fail to heal leading to incredible pain and debilitation [1,22]. The failure to progress through the phases of wound healing leads to deficient healing and they all certain characteristics such as increased oxidative stress, excessive protease activity and persistent recruitment of myeloid cells [23].…”