Proof-of-concept: 3D bioprinting of pigmented human skin constructs

Abstract

Three-dimensional (3D) pigmented human skin constructs have been fabricated using a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained from using three different types of skin cells (keratinocytes, melanocytes and fibroblasts from three different skin donors) and they exhibit similar constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop-on-demand bioprinting strategy facilitates the deposition of cell droplets to emulate the epidermal melanin units (pre-defined patterning of keratinocytes and melanocytes at the desired positions) and manipulation of the microenvironment to fabricate 3D biomimetic hierarchical porous structures found in native skin tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented skin constructs fabricated by conventional a manual-casting approach; in-depth characterization of both the 3D pigmented skin constructs has indicated that the 3D bioprinted skin constructs have a higher degree of resemblance to native skin tissue in term of the presence of well-developed stratified epidermal layers and the presence of a continuous layer of basement membrane proteins as compared to the manually-cast samples. The 3D bioprinting approach facilitates the development of 3D in vitro pigmented human skin constructs for potential toxicology testing and fundamental cell biology research.

From Shape to Function: The Next Step in Bioprinting

“…Such printed structures are particularly interesting as patches for skin transplantation, but also to study the barrier function of natural skin and for testing drug absorption and toxicity of cosmetics, as an alternative to animal experimentation. Indeed, bioprinted skin grafts have been produced including melanocyte‐laden bioinks to introduce pigmentation . Moreover, layering approaches provide opportunities to recreate a wide array of epithelial tissues and the basal lamina that support them, including but not limited to alveolar tissue in the lungs, cornea and urethral epithelium …”

3D organ models—Revolution in pharmacological research?

“…3D bioprinting offers features that overcome some of these bottlenecks, allowing one to print singularized cells in a highly automated and spatio-temporally controlled manner. Bioprinting has been employed for the fabrication of several organ models including human skin [35,36], lung [37,38] and liver [39] and recently also soft functional tissues including muscle [40] or kidney [41]. To take one example, engineered skin tissue requires specific cell-cell and cell-matrix interactions as well as precise positioning of cell layers.…”

Beyond 2D: 3D bioprinting for skin regeneration

“…Through histological analysis, they identified the formation of different skin layers and the existence of pigmentation . Wei Long Ng et al also successfully used FBs, KCs, and MCs to product 3D‐pigmented human skin constructs …”