Rethinking Chronic Wound Treatment: Unlocking the Potential of Combination Products for an Unmet Multifactorial Need: A Review Study.

Background and Aims: Chronic wounds, including diabetic foot, venous, and pressure ulcers, remain a major unmet medical challenge due to their prevalence, severity, and the limited efficacy of current treatments. These wounds are inherently multifactorial, requiring simultaneous intervention across all chronicity-inducing factors. Neither medical devices nor single pharmacological agents are sufficient, as they cannot comprehensively address the multiple therapeutic needs. This review aims to propose an integrative therapeutic approach capable of targeting all relevant mechanisms. Methods: A narrative review of the literature was conducted, analyzing over 100 peer-reviewed articles on chronic wound pathophysiology and therapeutic strategies. Sources were identified through searches in PubMed, Scopus, and Web of Science, complemented by manual reference screening. Studies discussing the mechanisms of wound chronicity, as well as drugs and biologics with potential therapeutic activity, were included. Results: The analysis revealed that current therapeutic options, including devices, drugs, and biologics, address only isolated aspects of chronic wound pathophysiology. No single agent or device is capable of comprehensively targeting all relevant mechanisms. However, evidence suggests that combining already-approved drugs and/or biologics may provide a synergistic effect, simultaneously targeting inflammation, infection, impaired angiogenesis, oxidative stress, and defective tissue remodeling. Importantly, the use of approved components leverages established pharmacological and safety profiles, potentially streamlining development and regulatory approval. Conclusion: A topical combination product integrating multiple agents offers a promising strategy to overcome the limitations of current treatments. Advances in the understanding of wound pathophysiology and the availability of diverse active molecules create new opportunities to design effective and holistic therapies. Such combination products could transform the management of chronic wounds and represent the next generation of treatment approaches.