One-step coordination of metal-phenolic networks as antibacterial coatings with sustainable and controllable copper release for urinary catheter applications.

Catheter-associated urinary tract infections (CAUTIs) draw great concern due to increased demand for urinary catheters in hospitalization. Encrustation caused by urinary pathogens, especially Proteus mirabilis, results in blocking of the catheter lumen and further infections. In this study, a facile and low-cost surface modification strategy of urinary catheters was developed using one-step coordination of tannic acid (TA) and copper ions. The copper content of the coating could be manipulated by the number of TA-Cu (TC) layers, and the coating released copper in a pH-responsive manner. The coating exhibited high antibacterial efficiency (killed >99% of planktonic bacteria, and reduced biofilm coverage to <1% after 24 h) due to the synergistic antimicrobial effect of TA and copper ions. In vivo study with a rabbit model indicated that with two TC layers, the coated catheter could effectively inhibit bacterial growth in urine and colonization on the surface, and reduce encrustation formation. In addition, the TC-coated catheter exhibited better tissue compatibility compared to the unmodified catheter, probably due to the antibacterial performance of the coating. Such a straightforward coating strategy with good in vitro and in vivo antibacterial properties and biocompatibility holds great promise for combating CAUTIs in clinical practice.

Tannic acid-reinforced zwitterionic hydrogels with multi-functionalities for diabetic wound treatment.

Diabetic wounds remain one of the most prevalent hard-to-heal wounds in the clinic. The causative factors impeding the wound healing process include not only the elevated oxidative stress and bacterial infections but also the high and repetitive plantar stress (including compressive pressure and shear stress). Conventional hydrogel dressings are mechanically weak and fragile, limiting their applications in the high stress-loading conditions of diabetic foot ulcers. As such, mechanically tough hydrogel dressings with appropriate bioactivities are highly desirable for diabetic wound treatment. In this study, a mechanically reinforced hydrogel with multiple biofunctionalities was developed via a facile and straightforward strategy of incorporation of tannic acid (TA) in zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogel. The polySBMA hydrogel reinforced by TA showed excellent mechanical property, with the tensile stress and compressive stress up to 93.7 kPa and 18.4 MPa, respectively, and it could resist cyclic compressive stress at ∼200 kPa (maximum in-shoe plantar pressure) for up to 3500 cycles. The TA-reinforced zwitterionic hydrogel exhibited strong adhesion to skin tissue (20.2 kPa), which was expected to reduce the shear stress on the foot. The plantar pressure on the foot was significantly reduced by the application of the resilient hydrogel. Attributed to the antioxidant and antibacterial properties of TA, the hydrogel showed rapid radical scavenging capability and strong bactericidal efficacy against Gram-positive and Gram-negative bacteria. In vitro and in vivo studies confirmed that the hydrogel has good cytocompatibility and negligible skin irritation, and promoted healing of diabetic wounds in mice. Such tough and effective hydrogel with a straightforward preparation strategy holds great promise as wound dressings for diabetic wound treatment.

The humanized nanobody RBD-1-2G tolerates the spike N501Y mutation to neutralize SARS-CoV-2

Neutralizing antibodies targeting the SARS-CoV-2 spike protein have shown a great preventative/therapeutic potential. Here, we report a rapid and efficient strategy for the development and design of SARS-CoV-2 neutralizing humanized nanobody constructs with sub-nanomolar affinities and nanomolar potencies. CryoEM-based structural analysis of the nanobodies in complex with spike revealed two distinct binding modes. The most potent nanobody, RBD-1-2G(NCATS-BL8125), tolerates the N501Y RBD mutation and remains capable of neutralizing the B.1.1.7 (Alpha) variant. Molecular dynamics simulations provide a structural basis for understanding the neutralization process of nanobodies exclusively focused on the spike-ACE2 interface with and without the N501Y mutation on RBD. A primary human airway air-lung interface (ALI) ex vivo model showed that RBD-1-2G-Fc antibody treatment was effective at reducing viral burden following WA1 and B.1.1.7 SARS-CoV-2 infections. Therefore, this presented strategy will serve as a tool to mitigate the threat of emerging SARS-CoV-2 variants.