Engineering in vitro models to replicate the complexity of chronic wounds

Chronic wounds represent a major clinical challenge driven by sustained inflammation, proteolytic imbalance, microbial colonisation, and impaired tissue regeneration. This review critically examines 2D and 3D in vitro models used in chronic wound research, evaluating their capacity to recapitulate chronicity across venous leg ulcers, diabetic foot ulcers, and pressure ulcers. Current systems lack the biochemical complexity required to reproduce key features of the non-healing phenotype. Building on quantitative clinical wound exudate data, we propose a feature-driven, aetiology-stratified framework that provides modular design considerations for in vitro models and chronic wound simulating media. Here, the authors review 2D and 3D in vitro chronic wound models and propose a feature-driven, aetiology-stratified framework that provides modular design considerations for in vitro models and chronic wound simulating media.