Over the last decades, three-dimensional (3D) organotypic skin models have received enormous attention as alternative models to in vivo animal models and in vitro two-dimensional assays. To date, most organotypic skin models have an epidermal layer of keratinocytes and a dermal layer of fibroblasts embedded in an extracellular matrix (ECM)-based biomaterial. The ECM provides mechanical support and biochemical signals to the cells. Without advancements in ECM-based biomaterials and biofabrication technologies, it would have been impossible to create organotypic skin models that mimic native human skin. In this review, the use of ECM-based biomaterials in the reconstruction of skin models, as well as the study of complete ECM-based biomaterials, such as fibroblasts-derived ECM and decellularized ECM as a better biomaterial, will be highlighted. We also discuss the benefits and drawbacks of several biofabrication processes used in the fabrication of ECM-based biomaterials, such as conventional static culture, electrospinning, 3D bioprinting, and skin-on-a-chip. Advancements and future possibilities in modifying ECM-based biomaterials to recreate disease-like skin models will also be highlighted, given the importance of organotypic skin models in disease modeling. Overall, this review provides an overview of the present variety of ECM-based biomaterials and biofabrication technologies available. An enhanced organotypic skin model is expected to be produced in the near future by combining knowledge from previous experiences and current research.
Keywords: 3D organotypic skin model; biofabrication; biomaterial; bioprinting; electrospinning; extracellular matrix; human skin equivalent; skin-on-a-chip.