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

Abstract

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BCTO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BCTO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BCTO-CHI and BCTO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BCTO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BCTO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BCTO-CHI. Furthermore, compared with blank hydrogels, BCTO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BCTO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BCTO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.

Cellulose–Chitosan Functional Biocomposites

“…Further, hydrogels based on chitosan and oxidised carboxymethylcellulose, optimised for controlled release of curcumin and used in the treatment of skin diseases, were developed by Dellali et al [ 103 ], and showed a positive antioxidant, antimicrobial, and proliferation impact. Hasan et al [ 104 ] prepared a bacterial cellulose–chitosan crosslinked hydrogel and loaded it with nitric oxide in the form of polyethyleneimine diazeniumdiolate (PEI/NO) for the treatment of polymicrobial wound infections. In this way, the improved NO loading enhanced bactericidal efficiency, and the sustained drug release lasted four days.…”

“…Therefore, there are many other approaches which use combinations of different formulations together with chitosan to improve its antimicrobial effects. Specifically, for wound dressings, many different formulations and approaches have been applied to improve their antibacterial activity, such as: silver formulations [ 138 , 139 ], zinc oxide [ 140 ], nitric oxide [ 104 ], ferulic acid [ 141 ], etc. Through carboxymethylation and selective oxidation of bacterial cellulose and cross-linking with chitosan, Xie et al produced a cellulose–chitosan wound dressing that inhibited bacterial proliferation and exhibited an 80% wound-healing rate after three weeks.…”

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon

“…31,32 Different from other NO releasing platforms with exogenous stimulations, the sustained release of NO was achieved with successive cycles of NO release from the disulfide bonding group reacting with GSH and SNAP, which are naturally present in the blood vessel. 33,34 Surface analysis of the multilayer-coated balloon system…”

Signaling pathways in cutaneous wound healing

“…Polymer matrices are of special interest for NO molecular systems functionalization due to their high versatility and similarities with living tissues (for review see work of Pinto et al, 2022). Recently, NO-releasing oxidized bacterial cellulose/chitosan crosslinked hydrogel was shown to eliminate polymicrobial wound infection, where linear polyethyleneimine diazeniumdiolate was used as the NO donor (Hasan et al, 2022). This newly developed NO-releasing hydrogel represents a promising approach for the treatment of various skin infections.…”