Ultrashort\nPeptides and Hyaluronic Acid-Based Injectable\nComposite Hydrogels for Sustained Drug Release and Chronic Diabetic\nWound Healing

Abstract

Peptide\nhydrogels are widely used for biomedical applications owing\nto their good biocompatibility and unique advantages in terms of amino\nacid-based structures and functions. However, the exploration of the\npeptide/saccharide composite hydrogels as potential biomaterials for\nchronic diabetic wound healing is still limited. Herein, hyaluronic\nacid (HA) was incorporated into diphenylalanine (FF) conjugated with\ndifferent aromatic moieties by a one-pot reaction. Our results showed\nthat the dipeptide derivatives modified by benzene (B), naphthalene\n(N), and pyrene (P) self-assembled into composite hydrogels with uniform\ndistribution and good mechanical properties in the presence of HA.\nThe obtained N-FF/HA composite hydrogel exhibited greatly improved\nself-healing properties <i>via</i> injection syringe needle\noperation and good biocompatibility on human skin fibroblast (HSF)\ncells. Besides, the structure of thinner nanofibers and honeycomb\nnetworks inside the composite hydrogel allowed for a longer sustained\nrelease of curcumin, a hydrophobic drug for anti-inflammation and\nwound healing. The curcumin-loaded N-FF/HA composite hydrogels could\npromote chronic wound healing in the streptozotocin-induced type I\ndiabetic mouse model. The results suggested that our developed saccharide-peptide\nhydrogels could serve as very promising synthetic biomaterials for\napplications in both drug delivery and wound healing in the future.