Bioengineering offers the potential to revolutionise the practice of dermatology and study of skin disease through the production of autologous organoids in vitro. The use of ECM-mimicking matrices has met with some success: commercial emulsion templated scaffolds have been used to model both wild type anatomy and skin cancer. Such scaffolds are however limited. They are only 200µm thick; the epidermal layer alone may be up to 1400µm deep endogenously. These models also lack any dermal adnexa; sweat glands, hairs, nerves, lymphatic or vascular systems. We have attempted to address elements of these shortcomings through the manufacture of an emulsion templated scaffold with a channelled architecture. A water-in-oil emulsion was formed by adding deionised water to an ethylhexylacrylate based organic solution. Layers of xanthan gum gel were incorporated into this simple emulsion. This was achieved using a custom modified and programmed extrusion 3D printer, forming a bi-continuous tri-phasic emulsion. An interconnected porous structure with a plexus of channels in horizontal and vertical planes was formed following photocuring. Channel sizes were shown to be readily modifiable through alteration of xanthan gum concentration. The 3D printing process allowed such channels to be formed in strategic configurations. This grid offers a putative vascular network enabling the scaffold to more closely mimic the endogenous dermal structure. Commercial scaffolds are, in part, of limited height as beyond 200µm thickness of packed cells there is a failure of diffusion of O2 leading to cellular necrosis. By incorporating a perfusable vascular network within the scaffold nutrients and metabolites may be readily redistributed. This in turn may enable the manufacture of full-thickness skin models more closely approximated in size and structure to endogenous human skin. These may be used to better understand dermal physiology, disease, and putative treatments.

Engineering the dermal vascular plexus