Recent Advances in the Local Drug Delivery Systems for Diabetic Wound Healing: A Comprehensive Review

Wound management in diabetic patients holds significant importance in both clinical and social contexts due to the delayed and compromised healing that these individuals experience. Diabetic wounds exhibit slow and incomplete healing, increasing patients' susceptibility to infections. Managing wounds in diabetic patients, particularly when complicated by diabetic foot infection or diabetic foot ulcer, becomes challenging. The ideal drug delivery systems for treating diabetic wounds should integrate diverse drugs and/or biological factors, offering advantages such as sustained and localized release of therapeutic compounds and enhanced wound healing outcomes. Several treatment modalities are under investigation for managing diabetic wounds, including advanced local drug delivery systems such as topical 3D scaffolds, particulate systems, and 3D scaffolds combined with particulate systems, in addition to gas therapy and skin grafts as advanced therapies. This review comprehensively discusses the state of the art for each treatment modality for diabetic wound healing associated with bioactive molecules. It also summarizes the forms of topically applied 3D scaffolds, including films, hydrogels, sponges, nanofibers, wafers, microneedles, and foams. The review differentiates their advantages and disadvantages as topical therapies while discussing various scaffold types that integrate therapeutic agents, which include polymeric, inorganic, composite, and biological scaffolds. With the emphasis on the newly investigated locally administered drug delivery systems for the management of diabetic wounds, the review also focuses on the challenges and the future perspectives for the production of such systems with the use of various drugs and biomaterials using innovative technologies such as 3D printing for effective healing of wounds.