Sprayable Zwitterionic Antibacterial Hydrogel With High Mechanical Resilience and Robust Adhesion for Joint Wound Treatment.

Wound healing in movable parts, including the joints and neck, remains a critical challenge due to frequent motions and poor flexibility of dressings, which may lead to mismatching of mechanical properties and poor fitting between dressings and wounds; thus, increasing the risk of bacterial infection. This study proposes a sprayable zwitterionic antibacterial hydrogel with outstanding flexibility and desirable adhesion. This hydrogel precursor is fabricated by combining zwitterionic sulfobetaine methacrylate (SBMA) with poly(sulfobetaine methacrylate-co-dopamine methacrylamide)-modified silver nanoparticles (PSBDA@AgNPs) through robust electrostatic interactions. About 150 s of exposure to UV light, the SBMA monomer polymerizes to form PSB chains entangled with PSBDA@AgNPs, transformed into a stable and adhesion PSB-PSB@Ag hydrogel at the wound site. The resulting hydrogel has adhesive strength (15-38 kPa), large tensile strain (>400%), suitable shape adaptation, and excellent mechanical resilience. Moreover, the hydrogel displays pH-responsive behavior; the acidic microenvironment at the infected wound sites prompts the hydrogel to rapidly release AgNPs and kill bacteria. Further, the healing effect of the hydrogel is demonstrated on the rat neck skin wound, showing improved wound closing rate due to reduced inflammation and enhanced angiogenesis. Overall, the sprayable zwitterionic antibacterial hydrogel has significant potential to promote joint skin wound healing.

Injectable hydrogel with antimicrobial and anti-inflammatory properties for postoperative tumor wound care.

Clinically, tumor removal surgery leaves irregularly shaped wounds that are susceptible to bacterial infection and further lead to excessive inflammation. Injectable hydrogel dressings with antimicrobial and anti-inflammatory properties have been recognized as an effective strategy to care for postoperative tumor wounds and prevent recurrence in recent years. In this work, we constructed a hydrogel network by ionic bonding interactions between quaternized chitosan (QCS) and epigallocatechin gallate (EGCG)-Zn complexes which were coordinated by EGCG and zinc ions. Because of the synergistic effect of QCS and EGCG-Zn, the hydrogel exhibited outstanding antimicrobial capacity (>99.9% inhibition), which could prevent infections caused byEscherichia coli and Staphylococcus aureus. In addition, the hydrogel was able to inhibit the growth of mice breast cancer cells (56.81% survival rate within 72 h) and reduce inflammation, which was attributed to the sustained release of EGCG. The results showed that the hydrogel was effective in inhibiting tumor recurrence and accelerating wound closure when applied to the postoperative tumor wounds. This study provided a simple and reliable strategy for postoperative tumor wound care using antimicrobial and anti-inflammatory injectable dressings, confirming their great potential in the field of postoperative wound dressings.

Metallic-Polyphenolic Nanoparticles Reinforced Cationic Guar Gum Hydrogel for Effectively Treating Burn Wound.

The development of injectable hydrogel dressings which are long-term moisturizing, easy-to-apply, and effectively inhibiting infection and inflammatory is essential to promote burn wound repairing. Herein, an injectable hydrogel with moisturizing, antibacterial, and anti-inflammation abilities via multiple reversible interactions between cation guar gum (CG) and metallic-polyphenolic nanoparticles (PA-ZnII NPs) is developed. Specifically, PA-ZnII NPs is formed by synergistic complexation of protocatechualdehyde (PA) and zinc ion (Zn2+ ), provides CGPZ hydrogel with plentiful reversible interactions to inhibit the loss of moist. By interacting with PA-ZnII NPs, the CGPZ hydrogel can provide enhanced moisturization for more than 3 days. Moreover, the CGPZ hydrogel can maintain good adhesion for a period of time with injection and self-healing capabilities due to reversible interactions between CG and PA-ZnII NPs. In addition, CGPZ hydrogel exhibits outstanding broad spectrum antibacterial performance, as its killing efficiency against Escherichia coli and Staphylococcus aureus is all greater than 99.99%. Importantly, compared with commercial dressing, the CGPZ hydrogel can promote wound healing faster by inhibiting tissue damage from dysregulated inflammation and accelerating neovascularization. It is believed that the moisturizing CGPZ hydrogel with antibacterial and anti-inflammation performance can serve as a promising dressing for the effective treatment of burn wound.

Zwitterionic silver nanoparticle based antibacterial eye drops for efficient therapy of bacterial keratitis.

Inefficient biofilm clearance and the risk of drug resistance pose significant challenges for antibiotic eye drops in the treatment of bacterial keratitis (BK). Recently, silver nanoparticles (AgNPs) have emerged as promising alternatives to antibiotics due to their potent antibacterial activity and minimal drug resistance. However, concerns regarding the potential biotoxicity of aggregated AgNPs in tissues have limited their practical application. In this study, polyzwitterion-functionalized AgNPs with excellent dispersion stability in the ocular physiological environment were chosen to prepare antibacterial eye drops. Zwitterionic AgNPs were synthesized using a copolymer, poly(sulfobetaine methacrylate-co-dopamine methacrylamide) (PSBDA), as a stabilizer and a reducing agent. The resulting antibacterial eye drops, named ZP@Ag-drops, demonstrated outstanding biocompatibility in in vitro cytotoxicity tests and in vivo rabbit eye instillation experiments, attributed to the zwitterionic PSBDA surface. Furthermore, the ZP@Ag-drops exhibited strong antibacterial activity against multiple pathogenic bacteria, particularly in penetrating and eradicating biofilms, due to the synergistic bactericidal effect of the released Ag+ and reactive oxygen species (ROS). Importantly, in vivo BK rabbit models showed that the ZP@Ag-drops effectively inhibited corneal infection and prevented ocular tissue damage, surpassing the therapeutic effect of commercial levofloxacin eye drops (LEV-drops). Overall, this study presents a promising alternative option for the effective treatment of BK using antibacterial eye drops.

Gelatin Sponges with a Uniform Interoperable Pore Structure and Biodegradability for Liver Injury Hemostasis and Tissue Regeneration.

Developing a hemostatic sponge that can effectively control bleeding from visceral injuries while guiding in situ tissue regeneration in incompressible wounds remains a challenge. Most of the existing hemostatic sponges degrade slowly, are relatively single-functioning, and cannot cope with complex environments. Herein, a biodegradable rapidly hemostatic sponge (GPZ) was created by dual-dynamic-bond cross-linking among Zn2+, protocatechualdehyde (PA)-containing catechol and aldehyde groups, and gelatin. GPZ had a uniformly distributed interconnected pore structure with excellent fluid absorption. It could effectively absorb the oozing blood and increase the blood concentration while stimulating platelet activation and accelerating blood coagulation. Compared to commercial hemostats, GPZ treatment significantly accelerated hemostasis in the rat liver defect model (∼0.33 min, ≥50% reduction in the hemostatic time) and in the rabbit liver defect model (∼1.02 min, ≥60% reduction in the hemostatic time). Additionally, GPZ had excellent antibacterial and antioxidant properties that effectively protected the wound from infection and excessive inflammation. In the liver regeneration model, GPZ significantly increased the rate of hepatic tissue repair and promoted rapid functional recovery without complications and adverse reactions. Overall, we designed a simple and effective biodegradable rapid hemostatic sponge with good clinical translational potential for treating lethal incompressible bleeding and promoting wound healing.

Multifunctional and Tunable Coacervate Powders to Enable Rapid Hemostasis and Promote Infected Wound Healing.

Hemostatic powders provide an important treatment approach for time-sensitive hemorrhage control. Conventional hemostatic powders are challenged by the lack of tissue adhesiveness, insufficient hemostatic efficacy, limited infection control, and so forth. This study develops a hemostatic powder from tricomponent GTP coacervates consisting of gelatin, tannic acid (TA), and poly(vinyl alcohol) (PVA). The physical cross-linking by TA results in facile preparation, good storage stability, ease of application to wounds, and removal, which provide good potential for clinical translation. When rehydrated, the coacervate powders rapidly form a cohesive layer with interconnected microporous structure, competent flexibility, switchable wet adhesiveness, and antibacterial properties, which facilitate the hemostatic efficacy for treating irregular, noncompressible, or bacteria-infected wounds. Compared to commercial hemostats, GTP treatment results in significantly accelerated hemostasis in a liver puncture model (∼19 s, >30% reduction in the hemostatic time) and in a tail amputation model (∼38 s, >60% reduction in the hemostatic time). In the GTP coacervates, gelatin functioned as the biodegradable scaffold, while PVA introduced the flexible segments to enable shape-adaptability and interfacial interactions. Furthermore, TA contributed to the physical cross-linking, adhesiveness, and antibacterial performance of the coacervates. The study explores the tunability of GTP coacervate powders to enhance their hemostatic and wound healing performances.

A zwitterionic silver nanoparticle-incorporating injectable hydrogel with a durable and efficient antibacterial effect for accelerated wound healing.

Antibacterial wound dressing is essential for inflammation control and accelerated wound healing. This study investigates polyzwitterion-functionalized silver nanoparticles (AgNPs) with enhanced antibacterial performance in an injectable wound dressing hydrogel. A mussel-inspired poly(sulfobetaine methacrylate-co-dopamine methacrylamide) (PSBDA) copolymer consisting of sulfobetaine and catechol moieties is developed and used in the stabilizing strategy for a facile one-step synthesis of AgNPs. The catechol moieties in PSBDA reduce AgNO3 in an alkaline solution and anchor PSBDA onto the surface of AgNPs. The zwitterionic AgNPs exhibit a uniform size profile and significantly improved stability, which are critical for maintaining antibacterial efficiency in a physiological environment. An injectable wound dressing hydrogel is developed by incorporating zwitterionic AgNPs into the mixed precursors of gelatin methacryloyl (GelMA) and poly(vinyl alcohol) (PVA). The hydrogel precursors exhibit good injectability and rapidly respond to UV-induced in situ gelation. The zwitterionic AgNP-incorporating hydrogel demonstrates significantly improved antibacterial efficiency compared to the non-zwitterionic counterpart both in vitro and in vivo. The zwitterionic modification also provides enhanced hemocompatibility and biocompatibility. The as-developed hydrogel dressing facilitates the resolution of inflammation and results in a rapid re-epithelization for the accelerated wound healing process in a rat full-thickness wound model.

Commercial soft contact lenses engineered with zwitterionic silver nanoparticles for effectively treating microbial keratitis.

The introduction of various drugs onto commercial soft contact lenses (CLs) has emerged as a potentially effective strategy for treating microbial keratitis (MK) because drug-loaded CLs can maintain a controlled drug concentration which leaded to enhanced drug bioavailability and reduced side effects in ocular tissues. In this study, silver nanoparticles modified with zwitterionic poly (carboxybetaine-co-dopamine methacrylamide) copolymer (PCBDA@AgNPs) as novel anti-infective therapeutics were prepared and firmly immobilized onto soft CLs through mussel-inspired surface chemistry. The obtained PCBDA@AgNPs coated CL (PCBDA@AgNPs-CL) remained the excellent transparency of commercial CLs and exhibited strong and broad-spectrum antimicrobial activities. We systematically explored the mechanism and found that the functional CLs can effectively inhibit the growth of microbial biofilms via a synergic "resist-kill-remove" strategy due to the zwitterionic surface and sustained release of silver ions. Significantly, in vitro cell cytotoxicity and in vivo subcutaneous implantation experiments proved the significant biosafety of PCBDA@AgNPs-CL. Furthermore, PCBDA@AgNPs-CL was successfully employed for the in vivo treatment of MK rabbit models, demonstrating excellent abilities to eradicate microbe-induced ocular infections and to prevent the destruction and irreversible structural alterations of corneal tissues. Collectively, PCBDA@AgNPs-CL is therefore a highly promising therapeutic device to significantly boost the efficacy for MK treatment.

A Uniform and Robust Bioinspired Zwitterion Coating for Use in Blood-Contacting Catheters with Improved Anti-Inflammatory and Antithrombotic Properties.

Inflammation and thrombosis are two major complications of blood-contacting catheters that are used as extracorporeal circuits for hemodialysis and life-support systems. In clinical applications, complications can lead to increased mortality and morbidity rates. In this work, a biomimetic erythrocyte membrane zwitterion coating based on poly(2-methacryloyloxyethyl phosphorylcholine-co-dopamine methacrylate) (pMPCDA) copolymers is uniformly and robustly modified onto a polyvinyl chloride (PVC) catheter via mussel-inspired surface chemistry. The zwitterionic pMPCDA coating exhibits excellent antifouling activity and resists bacterial adhesion, fibrinogen adsorption, and platelet adhesion/activation. The material also demonstrates great hemocompatibility, cytocompatibility, and anticoagulation properties in vitro. Additionally, this biocompatible pMPCDA coating reduces in vivo foreign-body reactions by mitigating inflammatory response and collagen capsule formation, due to its outstanding ability to resist nonspecific protein adsorption. More importantly, when compared with a bare PVC catheter, the pMPCDA coating exhibits outstanding antithrombotic properties when tested in an ex vivo rabbit perfusion model. Thus, it is envisioned that this biomimetic erythrocyte membrane surface strategy will provide a promising way to mitigate inflammation and thrombosis caused by the use of blood-contacting catheters.