A Review on Recent Progress and Clinical Translation of Self-Assembled Hydrogels in Diabetic Wound Repair

Abstract

Abstract Diabetic chronic wounds (DCWs) are difficult to heal due to the synergistic effects of bacterial infection, immune dysregulation, persistent oxidative stress, and microcirculatory impairment, posing a major challenge in tissue regeneration. Self-assembled hydrogels (SAHs), owing to their molecular programmability, tunable network architectures, and ability to respond to the pathological wound microenvironment, have demonstrated unique advantages in the repair of complex chronic wounds. This review summarizes the roles of various interactions, including hydrogen bonding, π-π stacking, metal coordination, hydrophobic interactions, electrostatic interactions, and dynamic covalent bonds, in constructing three-dimensional hydrogel networks. It further discusses the main design strategies and biological functionalities of SAHs, encompassing short peptides, polysaccharides, metal ions, nucleic acids, cyclodextrins (CDs), and dynamic covalent crosslinking materials. This review focuses on the pathological characteristics of DCWs and highlights recent research progress on SAHs in antibacterial, anti-inflammatory, antioxidative, immunomodulatory, pro-angiogenic, and tissue regeneration applications. Although various SAHs have demonstrated promising therapeutic efficacy in preclinical animal models, clinical practice still largely relies on conventional hydrogel formulations. Future efforts should focus on strengthening the integration between material design and pathological mechanisms, as well as establishing standardized evaluation frameworks, to facilitate the clinical translation of SAHs for the treatment of DCWs.