Preclinical models of diabetic wound healing: A critical review

Sanapalli, Bharat Kumar Reddy; Yele, Vidyasrilekha; Singh, Mantosh Kumar; Krishnamurthy, Praveen Thaggikuppe; Karri, Veera Venkata Satyanarayana Reddy

doi:10.1016/j.biopha.2021.111946

Cited by 29 publications

(26 citation statements)

References 126 publications

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“…The wound healing mechanism, even though it remains unclear, nevertheless enhanced blood flow, decreased inflammatory response, and reduced infection rates, all of which are contributing factors to angiogenesis. Rats are loose-skinned, in contrast to the tight human skin, with quicker constriction of the wound than the epithelization process; as such, rat wound healing, even though it is resemblant, is not entirely similar to wound healing in human skin [ 97 , 98 ]. However, rats are widely used animal models due to their genetic and behavioral similarity, ease of handling, and being economically viable.…”

Section: Resultsmentioning

confidence: 99%

Bio-Evaluation of the Wound Healing Activity of Artemisia judaica L. as Part of the Plant’s Use in Traditional Medicine; Phytochemical, Antioxidant, Anti-Inflammatory, and Antibiofilm Properties of the Plant’s Essential Oils

et al. 2022

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Artemisia judaica (ArJ) is a Mediterranean aromatic plant used traditionally to treat gastrointestinal ailments, skin diseases, atherosclerosis, and as an immuno-stimulant. This study describes ArJ essential oil constituents and investigates their wound healing activity. The in vitro antioxidant and antibiofilm activities of ArJ essential oil were investigated. The in vivo pro/anti-inflammatory and oxidative/antioxidant markers were compared with standard silver sulfadiazine (SS) in a second-degree skin burn experimental rat model. The gas chromatography-equipped flame ionization detector (GC-FID) analysis of ArJ essential oil revealed the major classes of compounds as oxygenated monoterpenes (>57%) and cinnamic acid derivatives (18.03%). The antimicrobial tests of ArJ essential oil revealed that Bacillus cereus, Candida albicans, and Aspergillus niger were the most susceptible test organisms. Two second-degree burns (each 1 inch square in diameter) were created on the dorsum of rats using an aluminum cylinder heated to 120 °C for 10 s. The wounds were treated either with ArJ or SS ointments for 21 days, while the negative control remained untreated, and biopsies were obtained for histological and biochemical analysis. The ArJ group demonstrated a significant increase in antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, while lipid peroxide (LP) levels remained insignificant compared to the negative control group. Additionally, ArJ and SS groups demonstrated a significant decrease in inflammatory levels of tumor necrosis factor α (TNF-α) compared to the negative group, while interleukin 1 beta (IL-1b) and IL-6 were comparable to the negative group. At the same time, anti-inflammatory IL-10 and transforming growth factor beta 1 (TGF-b1) markers increased significantly in the ArJ group compared to the negative control. The ArJ results demonstrated potent wound healing effects, comparable to SS, attributable to antioxidant and anti-inflammatory effects as well as a high proportion of oxygenated monoterpenes and cinnamate derivatives.

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Section: Resultsmentioning

confidence: 99%

Bio-Evaluation of the Wound Healing Activity of Artemisia judaica L. as Part of the Plant’s Use in Traditional Medicine; Phytochemical, Antioxidant, Anti-Inflammatory, and Antibiofilm Properties of the Plant’s Essential Oils

et al. 2022

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“…In such case, porcine models are commonly used to investigate new approaches for the treatment of wound infection. The skin structure of the pig is similar to human skin, and both pig and human wounds heal via re-epithelialization not by contractile healing [ 64 ]. However, limitations in using different animal models still exist as none of the models can completely mimic wound infection in humans [ 65 ].…”

Section: Reviewmentioning

confidence: 99%

Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice

Ding

Tang

et al. 2022

Burns &Amp; Trauma

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Acute and chronic wound infection has become a major worldwide healthcare burden leading to significantly high morbidity and mortality. The underlying mechanism of infections has been widely investigated by scientist, while standard wound management is routinely been used in general practice. However, strategies for the diagnosis and treatment of wound infections remain a great challenge due to the occurrence of biofilm colonization, delayed healing and drug resistance. In the present review, we summarize the common microorganisms found in acute and chronic wound infections and discuss the challenges from the aspects of clinical diagnosis, non-surgical methods and surgical methods. Moreover, we highlight emerging innovations in the development of antimicrobial peptides, phages, controlled drug delivery, wound dressing materials and herbal medicine, and find that sensitive diagnostics, combined treatment and skin microbiome regulation could be future directions in the treatment of wound infection.

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“…Although the stages of wound healing are similar and include coagulation, the inflammatory phase (immune cell infiltration, cytokine secretion), the proliferative phase (extracellular matrix generation, angiogenesis, epithelialization) and the remodeling phase (collagen crosslinking and reorganization), there are differences in skin ultrastructure and physiology between different species, which makes wound healing different in human and animals. In mice and rats, the skin is thin and fragile, whereas the subcutaneous layer consists of a special muscular striatum, panniculus carnosus (absent in humans), which causes more rapid contraction and facilitates wound healing [ 120 ]. Nevertheless, rodents are widely used in experimental models of diabetic wound healing and a number of them provided experience, which allows for further optimization of models in the aspects such as glycemic levels, the method of induction of DM, or duration of DM [ 121 ].…”

Section: Animal Models Versus Human Models—similarities and Differencesmentioning

confidence: 99%

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

Mieczkowski

Mrozikiewicz-Rakowska

Kowara

et al. 2022

IJMS

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Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement).

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Preclinical models of diabetic wound healing: A critical review

Cited by 29 publications

References 126 publications

Bio-Evaluation of the Wound Healing Activity of Artemisia judaica L. as Part of the Plant’s Use in Traditional Medicine; Phytochemical, Antioxidant, Anti-Inflammatory, and Antibiofilm Properties of the Plant’s Essential Oils

Bio-Evaluation of the Wound Healing Activity of Artemisia judaica L. as Part of the Plant’s Use in Traditional Medicine; Phytochemical, Antioxidant, Anti-Inflammatory, and Antibiofilm Properties of the Plant’s Essential Oils

Challenges and innovations in treating chronic and acute wound infections: from basic science to clinical practice

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

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