Bioprinted and manual human epidermis production: A compared performance for skin irritation tests

The progress of bioengineered skin models relies on increasing their human relevance and reliability as platforms to evaluate the safety of consumable products. 3D bioprinting allows the precise spatial control in the deposition of biological materials to achieve more relevant and representative skin mimetic models. Still, methodological comparison of bioprinting to the traditional manual dispersing system for in vitro reconstructed human epidermis (RHE) models is scarce in the literature. In this way, this study compares the performance of a bioprinted (B-RHE) to a manually (M-RHE) reconstructed human epidermis at the in vitro skin irritation test described in the Organization for Economic Co-operation and Development (OECD) guideline 439 (TG 439), that allows vitro hazard identification of irritant chemicals using validated RHE for safety assessment. Our results show that both models exhibited a well-stratified and multiple layered epidermis. The epidermal barrier function achieved equivalent performance standards to the validated RHE models described in TG 439. At in vitro irritation test, the performance of bioprinted epidermal models was similar to manual methodology as they correctly discriminated the selected reference substances classified as an irritant or non-irritant according to tissue viability threshold value (50%), which indicates that bioprinting can be of great contribution to the automation of reconstruction of epidermal models. However, a previously unpublished inflammatory response was significantly higher for the bioprinted methodology, even after the exposure to non-irritative substances. Therefore, although the bioprinted epidermal model is qualified to be used as a platform for the in vitro irritation test, the extrusion bioprinting that utilizes cylindrical needles can indirectly exacerbate inflammatory response. Finally, the ideal dispersing system must be considered for bioprinting tissue mimetics to be used as platforms to the evaluation of risk assessment.