Yutong Yuan, Shan Zhu, Yuanbo Liu, Yu Yao, Jing Zhang, X. Y. Li, Yuan Gao, Zilin Zhang, Bowen Song, Jun Ouyang, Juan Zhang, Qiwei L, Zaozao Chen, Zhonze Gu, Ningbei Yin, Nuo Si
Impaired wound healing and pathological scarring remain major clinical challenges, with immune cell dysregulation being a key driver of disease progression. Conventional in vitro models fail to recapitulate human immune responses, limiting their translational relevance. In recent years, advances in tissue engineering and microfluidic technologies have driven growing efforts to incorporate immune cells into in vitro models, thereby improving their ability to mimic pathological microenvironments. Among these, organ-on-a-chip technology stands out for its capacity to replicate dynamic perfusion, mechanical stimulation, and multicellular crosstalk-features critical for modeling immune-mediated wound repair. This review systematically summarizes recent progress in immune cell-integrated models of aberrant wound healing, including two-dimensional co-cultures, three-dimensional static cultures, organoid systems, and organ-on-a-chip platforms. We highlight core strategies for immune cell integration and their roles in recapitulating key pathological processes such as inflammation and fibrosis. Despite ongoing challenges in cell source stability, model standardization, and long-term culture viability, emerging strategies (e.g., organ-on-a-chip combined with three-dimensional bioprinting or modular design) offer new opportunities for creating biomimetic, high-throughput platforms for wound research. This review aims to facilitate the adoption of immune-integrated in vitro models in wound healing research, deepen mechanistic understanding of immune-driven pathology, and accelerate the development of precision therapeutics.