First-in-kind 3D bioprinted human skin model using recombinant human collagen

Abstract

Reliable translational human skin models are lacking for modeling skin diseases and screening effective therapeutics. 3D bioprinting is an emerging technology that enables the fabrication of human skin models that mimic the structure and functions of human skin in a dish (in-vitro). As a prototype, we present a first-in-kind fully humanized 3D bioprinted skin model as an alternative to animal testing for preclinical research. This model utilizes a plant-derived recombinant human collagen and human skin fibroblasts, melanocytes, and keratinocytes. The 3D bioprinted human skin model expresses involucrin and cytokeratin 14, contains melanin granules, and structurally resembles human skin. However, the morphology of keratinocytes is slightly different, containing a thicker layer of proliferative keratinocytes and a thinner layer of differentiated, cornified keratinocytes. Nevertheless, the model shows epidermal stratification, which indicates skin maturation. Further, the model lacks skin appendages such as hair follicles and sweat glands, as current bioprinting technology cannot deliver distinct cells at the single-cell resolution. Recent advances in 3D bioprinting such as spheroid-based bioprinting show potential to address these limitations. Hence, 3D bioprinting of skin using plant-derived recombinant human collagen, presents significant advantages, including high-throughput production of personalized human skin models, reduction of animal testing, and potential applications in regenerative medicine.