Dynamic biomimicry in skin-on-a-chip: multi-scale construction to translational dermatology, drug screening and cosmetic evaluation.

Abstract

Skin-on-a-chip has emerged as a promising platform for reconstructing human skin physiology <i>in vitro</i> with enhanced biological relevance. Unlike conventional static models, these systems can better reproduce key dynamic features of the skin microenvironment, including barrier maturation, mechanical stimulation, molecular transport, vascular exchange, immune activity, and system-level crosstalk. In this review, we examine recent advances in skin-on-a-chip from the perspective of dynamic biomimicry. We outline the major levels of dynamic biomimicry achieved in current platforms, spanning epidermal barrier models, mechanically responsive full-thickness systems, vascularized and immune-integrated platforms, and higher-order integrated models. We further discuss the main engineering strategies that support these functions, including chip architecture, biomimetic tissue construction, and vascularization. In addition, we highlight how increased dynamic fidelity expands the applications of skin-on-a-chip in disease modelling, drug screening, toxicity assessment, and cosmetic evaluation, while also discussing the remaining challenges in platform design, translational robustness, and industrial scalability. Finally, we outline future directions for developing more robust, integrated, and translatable skin-on-a-chip systems.