ChunMei Chen, XiaoMin Wang, Jia Guo, GuoLiang Chen, ShiMei Sun, Mei Wang, XiaoJi He
Diabetic wounds represent a major challenge in chronic wound management, owing to a constellation of pathological features including a hyperglycemic microenvironment, persistent inflammation, impaired angiogenesis, and heightened susceptibility to infection. Conventional wound dressings, limited by their single-function design, often fall short of meeting the demands of multi-target therapy. This review systematically surveys recent advances in diabetic wound healing, with a particular focus on emerging strategies such as natural bioactive small molecules, peptide-based therapeutics, self-assembling hydrogels, and exosomes. We begin by summarizing the pathophysiological mechanisms that underlie impaired diabetic wound healing, and then discuss the pharmacological activities and delivery barriers associated with five representative natural compounds and peptide-based agents. The strengths and limitations of self-assembling hydrogels as intelligent delivery platforms are critically assessed, alongside the unique contributions of exosomes in immunomodulation, angiogenesis promotion, and facilitation of cell migration. Building on these insights, we propose a synergistic therapeutic paradigm that integrates natural molecules/peptides, self-assembling hydrogels, and exosomes. The challenges of this integrated strategy-including standardized manufacturing, regulatory approval, and clinical translation-are further analyzed, providing a reference framework for the development of multifunctional wound dressings.