181 Full Skin Equivalent Model for Burn Wound Healing INTRODUCTION Wound healing of deep and large wounds is often problematic and can lead to medical complications such as hyper-inflammation and excessive scarring of the skin. In turn, these complications can lead to delayed recovery and poor aesthetic outcomes [1–4]. To improve the treatment of burn injuries, the processes underlying skin regeneration need to be better understood. Furthermore, there is a need for appropriate in vitro models to facilitate drug discovery and testing [5]. Research on cellular processes in burn wound healing is generally performed on animals [6–8]. Translation to the human situation is, however, difficult due to physiological differences between animals and humans [9,10]. In addition, in our modern society we strive for innovative, animal-free ways of conducting research [11]. Human studies, on the other hand, are limited by the absence of baseline values, heterogeneity among patients, and restrictions in the collection of tissue samples [6,7]. Therefore, there is an important demand for alternative models to study burn injuries. Organotypic skin models are useful alternatives to animal experimentation and can be used as a research instrument to study defined aspects of skin trauma, based on the behavior of human cells [12–14]. Moreover, these models are easily adjustable to study interactions of specific cell types and can be used to evaluate the effect of therapeutic interventions. Scratch models, in which a scratch is made in a monolayer of a single cell type, can be used to study cell migration and proliferation after wounding. However, such scratch models rely on a single type of cell, usually keratinocytes or fibroblasts [15]. Alternatively, 3D culture models can be used to study skin diseases [12–14,16–19]. 3D culture models resemble a more natural and complete environment for cells; however, they are often produced from hydrogels and seeded with immortalized cell lines or animal cells instead of primary isolated human cells. Furthermore, gel-based models are less suitable for the study of thermal trauma because they might not be strong enough to withstand the injury. More relevant and robust in vitro culture models for the study of wound healing are full skin equivalents produced from dermal scaffolds seeded with fibroblasts and keratinocytes [20,21]. Such FSEs are uniform, as there is less variation in the matrix, and more representative of the in vivo situation than the aforesaid culture models, because collagen is the predominant component [22]. FSEs produced from dermal collagen-elastin scaffolds provide a durable extracellular matrix architecture that supports cell anchorage [23,24]. In this study, we generated FSEs from the dermal substitutes MatriDerm® and Mucomaix®. These dermal matrices are clinically used in combination with split thickness 6
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