Unresolved challenges in wound healing: When science meets clinical need

Tissue damage is a natural consequence of mankind's interactions with the physical environment and leads to activation of endogenous repair mechanisms. Wound treatments developed over centuries, although largely empirical, have been incorporated into routine clinical practice while awaiting evidence of their efficacy. Based on a revisited and updated discussion from a 2013 Gordon Research Conference between basic scientists and clinicians, we outlined current knowledge of wound repair, emphasising the unique roles of diverse cell types including neutrophils, macrophages, keratinocytes, fibroblasts, and other previously overlooked lineages such as adipocytes and melanocytes. Five key clinical challenges remain unsolved: hypertrophic and keloid scarring, burns, wound infections, and chronic wounds. For each challenge, we reviewed recent basic science insights that offer potential therapeutic avenues, such as the role of inflammatory signals and mechanical cues in scarring, neutrophil dysfunction in burns, influence of the wound microbiome on infection, and epigenetic changes in chronic wounds. Although significant progress has been made, these topics remain problematic. We concluded by highlighting emerging research areas, including the overlooked roles of the nerves, fascia and fat tissue, and lessons from cancer biology, which may provide further opportunities to develop innovative strategies for wound care. By fostering greater collaboration and targeting a deeper understanding of mechanisms with unique models, the pathway to accelerate the translation of new therapies to improve patient outcomes is hopeful.