Impaired wound healing and pathological scarring remain major clinical challenges, closely linked to dysregulation of the immune microenvironment. Aberrant macrophage polarization, persistent neutrophil activation, and dysfunctional T cell regulation have been demonstrated to critically shape wound resolution and fibrotic outcomes. However, conventional in-vitro models fail to recapitulate human-relevant immune responses, thereby limiting mechanistic insights into wound healing pathology and hindering therapeutic translation.
Recent advances in tissue engineering, three-dimensional bioprinting, and microfluidic technologies have enabled the integration of immune components into engineered wound models, driving a transition from traditional culture systems toward immune-integrated microphysiological platforms. This review systematically summarizes the developmental trajectory, technical frameworks, and integration strategies of immune-inclusive wound-healing models, encompassing two-dimensional co-cultures, three-dimensional skin equivalents, organoid systems, and organ-on-a-chip technologies. We further highlight cell type-specific integration approaches for macrophages, neutrophils, T-cell subsets, and other immune populations, and discuss how these platforms recapitulate inflammation, fibrosis, angiogenesis, and immune-stromal crosstalk.
Organ-on-a-chip systems are particularly promising because they reproduce vascular perfusion, shear stress, and dynamic multicellular interactions, enabling more accurate modeling of immune cell trafficking and tissue remodeling. Hybrid microphysiological platforms combining organoids, 3D bioprinting, modular microfluidics, and multi-sensor integration provide enhanced spatial complexity, real-time monitoring capability, and long-term culture stability, thereby better capturing stage-specific immune regulation during wound repair.
Despite remaining challenges—including immune cell sourcing and stability, model standardization, long-term culture robustness, and engineering complexity—immune-integrated wound-healing models represent powerful tools for mechanistic investigation, drug screening, and precision therapeutic evaluation. Through interdisciplinary collaboration and standardized platform development, these next-generation systems are poised to shift wound-healing research from animal-based studies toward human-relevant precision-medicine platforms, accelerating advances in therapies for impaired wound healing and pathological scarring.

DOI：10.1093/procel/pwag013