The future of skin toxicology testing - Three-dimensional bioprinting meets microfluidics

Abstract

Over the years, the field of toxicology testing has evolved tremendously from the use of animal models to the adaptation of in vitro testing models. In this perspective article, we aim to bridge the gap between the regulatory authorities who performed the testing and approval of new chemicals and the scientists who designed and fabricated these in vitro testing models. An in-depth discussion of existing toxicology testing guidelines for skin tissue models (definition, testing models, principle, and limitations) is first presented to have a good understanding of the stringent requirements that are necessary during the testing process. Next, the ideal requirements of toxicology testing platform (in terms of fabrication, testing, and screening process) are then discussed. We envisioned that the integration of three-dimensional bioprinting within miniaturized microfluidics platform would bring about a paradigm shift in the field of toxicology testing; providing standardization in the fabrication process, accurate, and rapid deposition of test chemicals, real-time monitoring, and high throughput screening for more efficient skin toxicology testing.

Keywords: Additive manufacturing; Microfluidics; Skin bioprinting; Three-dimensional bioprinting; Three-dimensional printing.

Figure 1

Bioprinting facilitates the deposition of a monolayer of cells with homogeneous cell distribution[23]; the bioprinting technique can be used to fabricate reconstructed human epidermis or full-thickness skin models.

Figure 2

Histological and immunochemistry comparison of protein expression between bioprinted skin tissues and native human skin. (A) H and E staining, (B) DAPI staining of cell nuclei, (C) extracellular matrix proteins: Collagen I, VII and cell proliferation marker Ki67, (D) Epidermal differentiation proteins: Cytokeratin 15, filaggrin, cytokeratin 1, (E) Tight junction proteins: ZO-1, claudin I, e-cadherin. Scale bar = 100 µm. Reproduced with permission[40].

Figure 3

HP D300e digital dispenser that enables small volume dispensing for high-throughput deposition of test chemicals. Reproduced with permission from HP Inc.

Figure 4

A conceptual figure of important components in skin toxicology testing platform. (i) 3D bioprinting facilitates fabrication of complex 3D tissue models in a scalable and reproducible manner, (ii) automated deposition of test chemicals eliminate serial dilution step, reduce compound consumption and prevent compound cross-contamination, (iii) microfluidics platform provides controlled and dynamic culture conditions for maturation of functional tissue models and facilitates real-time, high-throughput screening through multiple arrays in parallel configuration.