3D bioprinted human skin tissue model to study scleroderma

Systemic Sclerosis (SSc) is a connective tissue disease of unknown pathogenesis characterised by autoimmunity, vasculopathy, and fibrosis due to hyperproliferation of fibroblasts and abnormal collagen deposition1,2. SSc is a progressive chronic, potentially fatal disease, producing a significant invalidity given by the progressive fibrosis of the skin (i.e., scleroderma), in the first place, and other target organs, such as lung and heart1,3. In recent years many animal models resembling clinical and biological phenotypes of SSc have been developed for the study of disease pathogenesis and related drug discovery; nevertheless, an accurate preclinical model of SSc is not yet available. The consequent inadequacy of these preclinical models makes drug development an obstacle race4,6. Moreover, the US government and the European Union, together with many other international organizations, strongly suggest enhancing replacement, reduction, and refinement of research on animal models. On the wave of obtaining accurate, reliable and affordable disease models, nowadays different tissue models are being developed for different diseases7. The development of skin tissue models, especially using 3D bioprinting, has already had some resonance in atopic dermatitis and other skin diseases8,9. Skin bioprinting may allow the generation of a skin surrogate to mirror tissue complexity and depict cellular interplay of SSc in a multidimensional model, thus representing a milestone in the study of disease pathogenesis and new drug discovery. To achieve this ambitious goal: i) first we plan to develop a 3D printed dermo-epidermal skin tissue equivalent using primary human dermal fibroblasts and epidermal keratinocytes; afterwards, the 3D printed construct will be stimulated with pro-inflammatory and pro-fibrotic factors to induce the pathological processes of SSc; ii) second, we aim to use, in our skin tissue bioink, primary cells derived from scleroderma skin, thus increasing the model’s resemblance to in vivo scleroderma. The herein described ‘Proof of Principle’ in vitro human skin tissue model, will provide a valid drug-screening platform for investigating novel potential therapeutic treatments against SSc, as an alternative to animal testing and in agreement with the principles of the 3Rs (i.e., replacement, reduction, refinement).