Non‐animal models of wound healing in cutaneous repair: In silico, in vitro, ex vivo, and in vivo models of wounds and scars in human skin

Abstract

Tissue repair models are essential to explore the pathogenesis of wound healing and scar formation, identify new drug targets/biomarkers and to test new therapeutics. However, no animal model is an exact replicate of the clinical situation in man as in addition to differences in the healing of animal skin; the response to novel therapeutics can be variable when compared to human skin. The aim of this review is to evaluate currently available non-animal wound repair models in human skin, including: in silico, in vitro, ex vivo, and in vivo. The appropriate use of these models is extremely relevant to wound-healing research as it enables improved understanding of the basic mechanisms present in the wound healing cascade and aid in discovering better means to regulate them for enhanced healing or prevention of abnormal scarring. The advantage of in silico models is that they can be used as a first in virtue screening tool to predict the effect of a drug/stimulus on cells/tissues and help plan experimental research/clinical trial studies but remain theoretical until validated. In vitro models allow direct quantitative examination of an effect on specific cell types alone without incorporating other tissue-matrix components, which limits their utility. Ex vivo models enable immediate and short-term evaluation of a particular effect on cells and its surrounding tissue components compared with in vivo models that provide direct analysis of a stimulus in the living human subject before/during/after exposure to a stimulus. Despite clear advantages, there remains a lack of standardisation in design, evaluation and follow-up, for acute/chronic wounds and scars in all models. In conclusion, ideal models of wound healing research are desirable and should mimic not only the structure but also the cellular and molecular interactions, of wound types in human skin. Future models may also include organ/skin-on-a-chip with potential application in wound healing research.

Isopropyl Caffeate: A Caffeic Acid Derivative—Antioxidant Potential and Toxicity

“…One way to predict the toxicity and pharmacokinetics of substances is through in silico tests, which assess the toxicity of theoretical compounds and aid in the choice of potentially promising molecules [ 11 , 12 , 36 ]. In silico tests revealed that isopropyl caffeate has no theoretical toxicity ( Table 3 ) and has probable activity against several diseases which are directly linked to oxidation ( Table 2 ).…”

“…It is worth noting that no chemical is free of toxicity; the study of toxic effects is as necessary as knowledge concerning side effects, interactions, contraindications, and mutagenicity [ 10 – 12 ]. Substance toxicity is often related to the formation of free radicals, which cause oxidative stress and are responsible for a large number of diseases [ 13 – 15 ].…”

The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing

“…In vivo models mimic human wound healing more efficiently. The widely utilized murine excisional wound model still has some disadvantages because it does not completely model human wound healing due to its inability to prevent skin contracture in rodents (Ud‐Din & Bayat, ). Therefore, we added a silicone splint to prevent unpredicted contracture and covered the wound with Tegaderm (H. Li, Cao, Huang, & Man, ) to maintain proper hydrophilicity (Persin et al, ).…”

Investigation of wound healing process guided by nano-scale topographic patterns integrated within a microfluidic system

“…Animal models have been widely used due to its advantages of comprehensive and systemic experiments [ 15 , 16 ], while they require specialized instruments and workforces to conduct wound healing study with well-controlled experimental environments [ 17 ]. In vitro wound healing models with a simple design, repeatability and low cost have been proposed to resolve these issues [ 18 , 19 ]. For in vitro wound formation methods, mechanical, electrical and optical wound formation have been studied to reproduce various types of wounds, e .…”