Nitric Oxide-Releasing Thermoresponsive Pluronic F127/Alginate Hydrogel for Enhanced Antibacterial Activity and Accelerated Healing of Infected Wounds

Abstract

Nitric oxide (NO), a highly reactive and lipophilic molecule, is one of the molecules present in the wound environment and implicated as an important regulator in all phases of wound healing. Here, we developed an NO-releasing thermoresponsive hydrogel (GSNO-PL/AL) composed of S-nitrosoglutathione (GSNO), pluronic F127 (PL), and alginate (AL) for the treatment of infected wounds. The GSNO was incorporated into the thermoresponsive PL/AL hydrogel, and differential scanning calorimetry techniques were used for the hydrogel characterization. The hydrogel was assessed by in vitro NO release, antibacterial activity, cytotoxicity, and wound-healing activity. The GSNO-PL/AL hydrogel demonstrated thermal responsiveness and biocompatibility, and it showed sustained NO release for 7 days. It also exhibited potent bactericidal activity against Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative multidrug-resistant Pseudomonas aeruginosa (MRPA). Moreover, the GSNO-PL/AL treatment of MRPA-infected wounds accelerated healing with a reduced bacterial burden in the wounds. The GSNO-PL/AL hydrogel would be a promising option for the treatment of infected wounds.

Exploration of Bioengineered Scaffolds Composed of Thermo-Responsive Polymers for Drug Delivery in Wound Healing

“…Regarding this, Cao et al developed a thermo-responsive hydrogel constituted by S-nitrosoglutathione, pluronic F127, and alginate, in which NO was incorporated for treating infected wounds. The scaffold demonstrated biocompatibility, sustained release of NO for seven days, and bactericidal activity against Staphylococcus aureus and Pseudomonas aeruginosa [ 216 ].…”

Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections

“…Previously, we developed several nitric oxide (NO) delivery systems for the treatment of bacteria-/biofilm-infected wounds ranging from nanoparticles (NPs), including bacteriatargeted NPs; microparticles; ointments; films; in situ and thermoresponsive hydrogels; and NO-doped polymers [8][9][10][11][12][13][14][15][16]. In recent years, NO has emerged as a potent antibacterial, antibiofilm, and wound healing enhancing agent.…”

Pluronic F-127/Silk Fibroin for Enhanced Mechanical Property and Sustained Release Drug for Tissue Engineering Biomaterial

“…The sol–gel transition of thermosensitive hydrogels can appear at a physiological temperature (~37 °C). Pluronic F-127 (PF) is one of the promising thermosensitive hydrogels which is used for various application [ 16 , 17 , 18 ]. PF is composed of an A-B-A non-ionic tri-block copolymer structure where A is a hydrophilic poly (ethylene oxide) (PEO) and B is a hydrophobic poly (propylene oxide) (PPO) [ 19 ].…”

“…To compensate the poor mechanical and physicochemical properties of PF, high concentrations of PF can be used but may result in undesirable side effects in vivo [ 25 ]. To overcome these problems, different types of polysaccharide and collagen-derived polymers such as hyaluronic acid, alginate, chitosan, gellan gum, and gelatin have been applied with PF to enhance the stability and physicochemical properties of PF through the intramolecular interaction [ 16 , 26 , 27 , 28 , 29 , 30 ]. A facile blending with various types of matrix exhibited a promising application as an injectable hydrogel for drug and cell delivery.…”