Ultrashort Peptides and Hyaluronic Acid-Based Injectable Composite Hydrogels for Sustained Drug Release and Chronic Diabetic Wound Healing

Abstract

Peptide hydrogels are widely used for biomedical applications owing to their good biocompatibility and unique advantages in terms of amino acid-based structures and functions. However, the exploration of the peptide/saccharide composite hydrogels as potential biomaterials for chronic diabetic wound healing is still limited. Herein, hyaluronic acid (HA) was incorporated into diphenylalanine (FF) conjugated with different aromatic moieties by a one-pot reaction. Our results showed that the dipeptide derivatives modified by benzene (B), naphthalene (N), and pyrene (P) self-assembled into composite hydrogels with uniform distribution and good mechanical properties in the presence of HA. The obtained N-FF/HA composite hydrogel exhibited greatly improved self-healing properties via injection syringe needle operation and good biocompatibility on human skin fibroblast (HSF) cells. Besides, the structure of thinner nanofibers and honeycomb networks inside the composite hydrogel allowed for a longer sustained release of curcumin, a hydrophobic drug for anti-inflammation and wound healing. The curcumin-loaded N-FF/HA composite hydrogels could promote chronic wound healing in the streptozotocin-induced type I diabetic mouse model. The results suggested that our developed saccharide-peptide hydrogels could serve as very promising synthetic biomaterials for applications in both drug delivery and wound healing in the future.

Short Peptide-Based Smart Thixotropic Hydrogels

“…As expected, the thixotropic property endowed the gel to be simply injected through a syringe and then returned to its gelled stated after injection. Deng et al also demonstrated the self-healing behavior of a composite hydrogel made of a series of aromatic-capped group (benzene, naphthalene, 2-anthracene, 9-anthracenemethoxycarbonyl, and 1-pyrene), with the most-studied being diphenylalanine (PhePhe) unit and a biocompatible natural polysaccharide, hyaluronic acid (HA) [ 180 ]. Out of these composite hydrogels, the N-PhePhe/HA gel showed better injectability and self-healing ability.…”

Hyaluronic Acid‐Based Injectable Hydrogels for Wound Dressing and Localized Tumor Therapy: A Review

“…For instance, Li et al reported dipeptide derivatives (diphenylalanine, FF) modified with aromatic moieties self‐assembled into composite hydrogels in the presence of HA and curcumin. [ 155 ] The prepared curcumin‐loaded N–FF (naphthalene–modified FF)/HA composite hydrogels not only showed improved self‐healing properties and good biocompatibility but also had sustained drug release effects at a slow rate within a long period. The diabetic mice wound healing results showed that the wound area decreased significantly in N–FF/HA/Cur hydrogels group when compared with blank N–FF/HA‐treated group on day 14 (5.48% ± 2.06% in N–FF/HA/Cur group vs. 11.71% ± 2.54% in N–FF/HA group, * P < 0.05).…”

Nanoscale bioconjugates: A review of the structural attributes of drug-loaded nanocarrier conjugates for selective cancer therapy

“…The HA donates biocompatibility and enhanced mechanical properties to the composite hydrogel. [ 165 ] a Phosphatase, b esterase, c diphenylalanine, d hyaluronic acid. …”