Biomimiq’s services are based on in vitro human skin equivalents (HSEs). These are living equivalents of healthy and diseased human skin.
Isolated cultures of primary skin cells and established skin cell lines lack a relevant and organized microenvironmental context. Advanced three-dimensional in vitro models of human skin integrate skin cells in a relevant microenvironment. In literature, these models are designated three-dimensional, full-thickness, organotypic, (bio)engineered or reconstructed human skin equivalents (HSEs), models, constructs or rafts.
Three-dimensional in vitro HSEs contain an epidermal compartment and a dermal compartment. The epidermal compartment harbors epidermal cells of any origin, including healthy, diseased or transformed primary keratinocytes, established epidermal cell lines or complete primary skin (disease) explants. The dermal compartment of HSEs may be composed of any biological or artificial matrix representing human dermis, including rat-tail type I collagen, human fibroblast-derived matrix (FDM), de-epidermized human dermis (DED) or artificial matrix. The dermal matrix may be either acellular or seeded with any type of human stromal cell, including healthy or disease-associated human dermal fibroblasts, endothelial cells or immune cells. The epidermal and dermal compartments of HSEs are separated by a fully functional basement membrane (BM).
Figure 1 | Schematic overview of Biomimiq's full thickness human skin equivalent (HSE) generation technology.
Step by step culturing
In vitro HSEs are sophisticated cell culture systems. In general, the dermal compartment is prepared and seeded with stromal cells before adding the epidermal compartment. Depending on the type of matrix, this may take one to four weeks (Figure 2). In this phase, the culture medium is optimized towards creating a dermal microenvironment capable of fully supporting the prospective epidermal compartment. Next, the epidermal compartment is added to the culture system. The cultures are then kept submerged in culture medium to promote attachment of epidermal cells to the dermal compartment and to stimulate proliferation of the epidermal cells to form a three-dimensional multilayered epidermis. This submerged culture period typically covers four to seven days allowing a functional BM to form. Subsequently, the three-dimensional models are cultured at the air-liquid interface, leaving the epidermal compartment air-exposed to stimulate cellular differentiation. The air-exposed culture period typically spans two weeks, but may range from one to twenty weeks depending on the type of model and the research question.
Figure 2 | Schematic overview of the main technological difference between Biomimiq's basic full-thicknes human skin equivalents (HSEs). Fibroblast-derived matrix (FDM) skin models are generated on a fully human fibroblast-derived matrix (top panel), whereas basic full thickness skin models (FTM) are based on a fibroblast-seeded rat tail collagen matrix (bottom panel).