A novel bola-molecular self-assembling hydrogel for enhancing diabetic wound healing

Hypothesis: Chronic wounds, particularly those caused by diabetes, pose a significant challenge for clinical treatment due to their prolonged healing process and associated complications, which can lead to increased morbidity. A biocompatible hydrogel with strong antibacterial properties and the ability to promote angiogenesis can be directly absorbed in the wound site for healing. Experiments: A series of self-healing, antibacterial bolaamphiphilic supramolecular self-assembling hydrogels (HLQMes/Cu) were developed based on metal-ligand coordination between various concentrations of Cu2+ solution and the head group of L-histidine methyl ester in HLQMes. This is the first report on the application of bola-molecular supramolecular hydrogels for the treatment of chronic wounds. Findings: The bola-molecular hydrogels reduced the toxicity of copper ions by coordination, and the HLQMes/Cu hydrogel, with 1.3 mg/mL Cu2+ (HLQMes/Cu1.3), demonstrated good biocompatibility and antibacterial properties and effectively enhanced wound healing in a diabetic wound model with full-thickness injuries. Immunohistochemical analysis revealed that the HLQMes/Cu1.3 hydrogel enhanced epithelial formation and collagen deposition in wounds. Immunofluorescence studies confirmed that the HLQMes/Cu1.3 hydrogel attenuated the expression of proinflammatory factor (IL-6) and promoted angiogenesis by upregulating alpha-SMA