Polymeric materials releasing nitric oxide have attracted significant attention for therapeutic use in recent years. As one of the gaseous signaling agents in eukaryotic cells, endogenously generated nitric oxide (NO) is also capable of regulating the behavior of bacteria as well as biofilm formation in many metabolic pathways. To overcome the drawbacks caused by the radical nature of NO, synthetic or natural polymers bearing NO releasing moiety have been prepared as nano-sized materials, coatings, and hydrogels. To successfully design these materials, the amount of NO released within a certain duration, the targeted pathogens and the trigger mechanisms upon external stimulation with light, temperature, and chemicals should be taken into consideration. Meanwhile, NO donors like S-nitrosothiols (RSNOs) and N-diazeniumdiolates (NONOates) have been widely utilized for developing antimicrobial polymeric agents through polymer-NO donor conjugation or physical encapsulation. In addition, antimicrobial materials with visible light responsive NO donor are also reported as strong and physiological friendly tools for rapid bacterial clearance. This review highlights approaches to delivery NO from different types of polymeric materials for combating diseases caused by pathogenic bacteria, which hopefully can inspire researchers facing common challenges in the coming ‘post-antibiotic’ era.

Hemorrhage is the leading cause of preventable death of injured military and civilian patients, and subsequent infection risks endanger their lives or impede the healing of their wounds. Here, we report an injectable biodegradable hydrogel with hemostatic, antimicrobial, and healing-promoting properties. The hydrogel was prepared by dynamic cross-linking of a natural polysaccharide (dextran) with antimicrobial peptide ε-poly-L-lysine (EPL) and encapsulating base fibroblast growth factor (bFGF). The amino groups of EPL were allowed to react with the aldehyde of oxidized dextran (OD) through the Schiff-base reaction for the generation of hydrogels that have fast self-healing and injectable characteristics and adapt to the shapes of wounds. The prepared OD/EPL hydrogels promoted blood clotting in vitro and stopped bleeding in a rat liver injury model within 6 min through their platelet-aggregating ability and sealing effect. These hydrogels exhibited inherent antimicrobial effects without the use of antibiotics and effectively killed a broad spectrum of pathogenic microbes, including Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli, and Pseudomonas aeruginosa and fungus Candida albicans in vitro. Moreover, these OD/EPL hydrogels were compatible with mammalian cells in vitro and in vivo and biodegradable in the mouse body. The loaded bFGF can be released sustainably, and it can promote angiogenesis, endothelial cell migration, and consequently accelerate the healing of wounds. The OD/EPL hydrogel inhibited MRSA infection in a rat full-thickness skin wound model and promoted healing. This kind of multifunctional hydrogel is a promising wound dressing for the emergency treatment of acute deep or penetrating injuries.

Diabetes is a chronic metabolic disease characterized by high glucose concentration in blood. Conventional management of diabetes requires skin pricking and subcutaneous injection, causing physical pain and physiological issues to diabetic individuals. Hydrogels possess unique advantages such as lightweight, stretchability, biocompatibility, and biodegradability, offering the opportunities to be integrated as flexible devices for diabetes management. This review highlights the development of hydrogels as flexible materials for diabetes applications in glucose monitoring, insulin delivery, wound care, and cell transplantation in recent years. Challenges and prospects in the development of hydrogel-based flexible devices for personalized management of diabetes are discussed as well.

Hydrogen sulfide (H₂S) plays an important role in regulating various pathological processes such as protecting mammalian cell from harmful injuries, promoting tissue regeneration, and regulating the process of various diseases caused by physiological disorders. Studies have revealed that the physiological effects of H₂S are highly associated with its concentrations. At relatively low concentration, H₂S shows beneficial functions. However, long-time and high-dose donation of H₂S would inhibit regular biological process, resulting in cell dysfunction and apoptosis. To regulate the dosage of H₂S delivery for precision medicine, H₂S delivery systems with intelligent characteristics were developed and a variety of biocompatibility polymers have been utilized to establish intelligent polymeric H₂S delivery systems, with the abilities to specifically target the lesions, smartly respond to pathological microenvironments, as well as real-timely monitor H₂S delivery and lesion conditions by incorporating imaging-capable moieties. In this review, we focus on the design, preparation, and therapeutic applications of intelligent polymeric H₂S delivery systems in cardiovascular therapy, inflammatory therapy, tissue regenerative therapy, cancer therapy and bacteria-associated therapy. Strategies for precise H₂S therapies especially imaging-guided H₂S theranostics are highlighted. Since H₂S donors with stimuli-responsive characters are vital components for establishing intelligent H₂S delivery systems, the development of H₂S donors is also briefly introduced.