Recent Developments in Multifunctional Antimicrobial Surfaces and Applications toward Advanced Nitric Oxide-Based Biomaterials

Abstract

Implant-associated infections arising from biofilm development are known to have detrimental effects with compromised quality of life for the patients, implying a progressing issue in healthcare. It has been a struggle for more than 50 years for the biomaterials field to achieve long-term success of medical implants by discouraging bacterial and protein adhesion without adversely affecting the surrounding tissue and cell functions. However, the rate of infections associated with medical devices is continuously escalating because of the intricate nature of bacterial biofilms, antibiotic resistance, and the lack of ability of monofunctional antibacterial materials to prevent the colonization of bacteria on the device surface. For this reason, many current strategies are focused on the development of novel antibacterial surfaces with dual antimicrobial functionality. These surfaces are based on the combination of two components into one system that can eradicate attached bacteria (antibiotics, peptides, nitric oxide, ammonium salts, light, etc.) and also resist or release adhesion of bacteria (hydrophilic polymers, zwitterionic, antiadhesive, topography, bioinspired surfaces, etc.). This review aims to outline the progress made in the field of biomedical engineering and biomaterials for the development of multifunctional antibacterial biomedical devices. Additionally, principles for material design and fabrication are highlighted using characteristic examples, with a special focus on combinational nitric oxide-releasing biomedical interfaces. A brief perspective on future research directions for engineering of dual-function antibacterial surfaces is also presented.

Synthesis and Characterization of Nitric Oxide-Releasing Ampicillin as a Potential Strategy for Combatting Bacterial Biofilm Formation

“…By conjugating a NO-donating SNAP moiety to conventional antibiotics, both the therapeutic benefits of NO and the conventional antibiotic may be delivered concomitantly for localized effect against both planktonic bacteria and biofilms. Furthermore, incorporation of an RSNO group in lieu of N -diazeniumdiolates or other NO donors offers the potential for improved controlled release of NO, as RSNOs have shown improved stability over N -diazeniumdiolates and many other NO donors under physiological conditions. , Contemporary application of RSNOs such as S -nitrosoglutathione (GSNO), SNAP, and S -nitroso- N -acetyl- L -cysteine ethyl ester (SNACET) in lock solutions and other therapies has shown their utility for developing prolonged, stable release of NO under physiological conditions, unlike N -diazeniumdiolate counterparts, which exhibit cytotoxic levels of NO burst release with additional cytotoxicity concerns from polyamine byproduct formation. − …”

“…Furthermore, incorporation of an RSNO group in lieu of N-diazeniumdiolates or other NO donors offers the potential for improved controlled release of NO, as RSNOs have shown improved stability over N-diazeniumdiolates and many other NO donors under physiological conditions. 38,39 Contemporary application of RSNOs such as S-nitrosoglutathione (GSNO), SNAP, and S-nitroso-N-acetyl-L-cysteine ethyl ester (SNACET) in lock solutions and other therapies has shown their utility for developing prolonged, stable release of NO under physiological conditions, unlike N-diazeniumdiolate counterparts, which exhibit cytotoxic levels of NO burst release with additional cytotoxicity concerns from polyamine byproduct formation. 40−42 Herein, covalent conjugation of the tertiary RSNO NO donor SNAP to the clinically ubiquitous, broad-spectrum antibiotic ampicillin is performed to form a novel therapy with SNAPicillin.…”

Driving Polymer Brushes from Synthesis to Functioning

“…The formation of biofouling happening in complex fluids such as saliva, blood, and tissue medium, is usually composed of three stages: (i) Nonspecific adsorption of biomacromolecules such as protein; (ii) Sparse adhesion of bacteria or body cells; (iii) Formation of biofilm. [211][212][213][214][215] The construction of the hydrated polymer brush layer, which mainly depends on surface hydrophilicity, is a conventional strategy to prevent initial protein adsorption, followed by reduced cell or bacteria adhesion. [216][217][218] The hydration layer can be formed by the interaction between hydrophilic groups and water, which presents stereoscopic repulsion to reduce nonspecific adsorption.…”

Inclusion Complexation of S-Nitrosoglutathione for Sustained Nitric Oxide Release from Catheter Surfaces: A Strategy to Prevent and Treat Device-Associated Infections

“…Second, solid NO donors are embedded in nanoparticles and polymers, allowing for controlled release of NO from storable nanocarriers and devices . A large number of publications focus on the functionalization of polymeric devices such as catheters, grafts, cannulas, and sensors with NO donors or NO-donating moieties to reduce device-associated complications. ,,− Third, aqueous solutions, suspensions, and hydrogels containing NO donors are suited to be administered via intranasal, intramuscular, intracameral routes, or topically for therapeutic purposes. − They have also been employed as filling solutions for implants, such as catheters, − representing a unique method to release protective NO without modifying the polymers of medical implants.…”