Engineering the Healing Process: Advanced In Vitro Wound Models and Technologies

Advances in regenerative medicine increasingly rely on human-relevant in vitro systems to model the multistage process of wound healing. However, the translation of research into effective therapies remains limited by the inability of traditional 2D cultures and animal models to faithfully replicate the structural and biochemical complexity of human skin. While existing reviews often focus on the structural composition of static skin equivalents, this review addresses a critical knowledge gap: the need for dynamic, time-dependent methodologies that can capture the spatiotemporal evolution of healing, from inflammation to remodeling, in both physiological and pathological conditions. To this end, we critically evaluate next-generation platforms, including 3D bioprinting, organ-on-chip systems, organoids, and iPSC-based models, highlighting their comparative advantages and technical hurdles like vascularization and scalability. The unique contribution of this work lies in providing a forward-looking framework that advocates for the convergence of bioengineering and computational modeling to move beyond “steady-state” snapshots toward predictive, high-resolution dynamic models. We conclude that the future of wound healing research depends on integrating vascular and immune components within these platforms to achieve truly human-relevant, personalized diagnostic and therapeutic tools.