193 Full Skin Equivalent Model for Burn Wound Healing As seen only in ex vivo human skin cultures, the level of IL-1β, IL-10, and IP-10 gradually decreased over time. These cytokines might have been produced by immune cells, such as lymphocytes, that were residing in the ex vivo skin. With increasing culture time, cytokine production would then be reduced due to migration or depletion of these cells. Burn injury had only a limited effect on the level of cytokines and seemed to moderately increase the levels of IL-4, IL-6, IL-8, IL-10, and TGF-β1 in MatriDerm- and Mucomaix-based models early after injury. Possibly, the effect of burn injury was minimal because of the initially high levels in uninjured models. An increase in IL-8 in medium of burn-injured in vitro skin models was shown by Breetveld et al. and was only present early after injury (up to 4 days) [39]. A study from Schneider et al. showed an increase in the levels of IL-6 and IL-8 in similar models, also during the first week after injury [48]. The limited effect of burn injury on these models is likely caused by the absence of blood circulation and immune cells, which are well-known inducers of immune reactions. Because the thermal injury damaged a large portion of cells in these relatively small models, the potential response could only originate from the remaining viable cells. When the population of remaining cells is too small, the response will also be rather limited. The current FSEs are useful for the study of tissue development and repair and for translational research without the use of animal models [33,49]. When fibroblasts and keratinocytes are kept in frozen stock, these models can be produced on demand, unlike ex vivo skin models, which depend on the availability of donor skin. FSEs are also advantageous because they are more standardized, can minimize donor variation, and are easily adjustable in terms of matrix, cell types, and cell numbers. The next step in the development of in vitro skin models will be the integration of immune cells, blood vessels, or other relevant skin appendages [50–53] and developing models suitable for drug discovery and testing [54]. Cells from different (disease-related) origins, such as skin cells derived from fetal, burn, or scar tissue, could be used to study their effect on skin regeneration. For example, van den Broek et al. developed a hypertrophic scar model using adipose-derived mesenchymal stem cells [55]. In these scar models, differences in contraction, epidermal thickness, and cytokine response were shown compared to models produced from dermal mesenchymal cells. To study inflammatory responses in a more relevant environment, immune cells can be integrated into FSEs [56]. Finally, such models could be supplemented with skin appendages such as hair follicles, making these models a useful platform to test interventions in the preclinical stage. Clinically applied matrices MatriDerm and Mucomaix are suitable materials for in vitro skin model development. MatriDerm-based FSEs could be used for extensive culture periods and demonstrated regeneration after thermal wounding. The cytokine response 6
RkJQdWJsaXNoZXIy MTk4NDMw