This review by Mahrukh Riaz and her colleagues Muhammad Zohaib Iqbal, Dr. Thomas Biedermann, and Dr. Agnes S. Klar (Tissue Biology Research Unit, Department of Surgery, University Children’s Hospital Zurich; University of Zurich) systematically analyses and structures recent discoveries linking immune dysregulation to chronic, non-healing wounds such as diabetic foot ulcers, pressure ulcers, and venous leg ulcers. Through the in-depth analysis of recent studies, the authors found that persistent inflammation and impaired immune resolution are the central drivers of chronic wound pathology. They highlighted how excessive activity of neutrophils and M1 macrophages, coupled with a lack of transition to reparative M2 macrophages, leads to tissue destruction and stalled healing. Moreover, T-cell imbalances, including overactivation of cytotoxic T cells and inadequate regulatory T-cell response, further sustain chronic inflammation and delay tissue repair.
The authors identified a strong link between protease overexpression and extracellular matrix degradation, showing how this biochemical imbalance prevents proper granulation and re-epithelialization. Their synthesis also reveals that vascular dysfunction and impaired angiogenesis contribute to poor oxygenation and nutrient delivery, creating a microenvironment hostile to regeneration.
Importantly, the study presents emerging immunomodulatory therapeutic strategies that can help restore immune balance and promote healing. These include:
The authors further emphasize the translational and clinical relevance of these findings, bridging preclinical models with patient-based therapies. The study identifies major translational challenges in chronic wound therapy, including patient heterogeneity, which limits universal treatment efficacy due to varied immune profiles. It emphasizes the importance of timing interventions to match specific healing phases and avoid disrupting immune balance. Furthermore, it highlights the need for immune-phenotype–tailored therapies, where treatments are personalized based on individual immune responses. These insights advocate for precision immunomodulation to enhance healing outcomes and advance personalized medicine in chronic wound management.
Collectively, this paper provides a comprehensive framework that connects immune dysregulation, chronic inflammation, and regenerative failure in non-healing wounds. It underscores the promise of targeting immune pathways to shift chronic wounds from a persistent inflammatory state toward successful tissue regeneration, paving the way for next-generation immunotherapeutic wound treatments.
See the article: Immunomodulatory Mechanisms of Chronic Wound Healing: Translational and Clinical Relevance
https://doi.org/10.1002/mco2.70378
MedComm
Immunomodulatory Mechanisms of Chronic Wound Healing: Translational and Clinical Relevance
20-Oct-2025