Experimental burn models are essential tools for simulating human burn injuries and exploring the consequences of burns or new treatment strategies. Unlike clinical studies, experimental models allow a direct comparison of different aspects of burns under controlled conditions and thereby provide relevant information on the molecular mechanisms of tissue damage and wound healing, as well as potential therapeutic targets. While most comparative burn studies are performed in animal models, a few human or humanized models have been successfully employed to study local events at the injury site. However, the consensus between animal and human studies regarding the cellular and molecular nature of systemic inflammatory response syndrome (SIRS), scarring, and neovascularization is limited. The many interspecies differences prohibit the outcomes of animal model studies from being fully translated into the human system. Thus, the development of more targeted, individualized treatments for burn injuries remains a major challenge in this field. This review focuses on the latest progress in experimental burn models achieved since 2016, and summarizes the outcomes regarding potential methodological improvements, assessments of molecular responses to injury, and therapeutic advances.

Comparative studies of human tissue damage caused by burns are challenging because precise information regarding the temperature, time, and duration of the exposure is often missing. Animal models cannot be fully translated to the human system due to interspecies differences in cutaneous tissues. We used a human composite tissue model to compare tissue damage caused by thermal burns with different dynamics. Equal subcutaneous/cutaneous composite tissue samples from six donors were first exposed to either preheated steel (100 °C) or a precision flame burner (300 °C) and were then maintained in vitro for seven days. Histological and immunohistochemical analyses revealed that flame burns instantly caused deep and stable damage to the subcutaneous tissue, which stayed constant for seven days. By contrast, contact burns inflicted tissue damage that was initially superficial but then expanded deeper into the adipose tissue. This spatiotemporal expansion of tissue damage was essentially accompanied by macrophage and fibroblast activation, which points towards inflammation resolution and wound healing. Our study suggests that thermal differences in burns directly influence the course of tissue damage, the cellular response and, consequently, the likely dynamics of repair processes days after burn injuries.

Age-related loss of skeletal muscle is associated with obesity and inflammation. In animal models, intramuscular fat deposits compromise muscle integrity; however, the relevant fat components that mediate muscular inflammation are not known. Previously, we hypothesized that free fatty acids (FFAs) may directly induce inflammatory gene expression in skeletal muscle cells of obese rats. Here, we examined this hypothesis in primary human skeletal myoblasts (SkMs) using multiplex expression analysis of 39 inflammatory proteins in response to different FFA species. Multiplex mRNA quantification confirmed that the IL6, IL1RA, IL4, LIF, CXCL8, CXCL1, CXCL12 and CCL2 genes were differentially regulated by saturated and unsaturated C16 or C18 FFAs. Fluorescence staining revealed that only saturated C16 and C18 strongly interfere with myoblast replication independent of desmin expression, mitochondrial abundance and oxidative activity. Furthermore, we addressed the possible implications of 71 human receptor tyrosine kinases (RTKs) in FFA-mediated effects. Phosphorylated EphB6 and TNK2 were associated with impaired myoblast replication by saturated C16 and C18 FFAs. Our data suggest that abundant FFA species in human skeletal muscle tissue may play a decisive role in the progression of sarcopenic obesity by affecting inflammatory signals or myoblast replication.

Findings from studies of muscle regeneration can significantly contribute to the treatment of age-related loss of skeletal muscle mass, which may predispose older adults to severe morbidities. We established a human experimental model using excised skeletal muscle tissues from reconstructive surgeries in eight older adults. Muscle samples from each participant were preserved immediately or maintained in agarose medium for the following 5, 9, or 11 days. Immunofluorescence analyses of the structural proteins, actin and desmin, confirmed the integrity of muscle fibers over 11 days of maintenance. Similarly, the numbers of CD80-positive M1 and CD163-positive M2 macrophages were stable over 11 days in vitro. However, the numbers of PAX7-positive satellite cells and MYOD-positive myoblasts changed in opposite ways, suggesting that satellite cells partially differentiated in vitro. Further experiments revealed that stimulation with unsaturated fatty acid C18[2]c (linoleic acid) increased resident M1 macrophages and satellite cells specifically. Thus, the use of human skeletal muscle tissue in vitro provides a direct experimental approach to study the regulation of muscle tissue regeneration by macrophages and stem cells and their responses to therapeutic compounds.