Biomimetic zwitterionic copolymerized chitosan as an articular lubricant.

Restoration of the lubrication functions of articular cartilage is an effective treatment to alleviate the progression of osteoarthritis (OA). Herein, we fabricated chitosan-block-poly(sulfobetaine methacrylate) (CS-b-pSBMA) copolymer via a free radical polymerization of sulfobetaine methacrylate onto activated chitosan segment, structurally mimicking the lubricating biomolecules on cartilage. The successful copolymerization of CS-b-pSBMA was verified by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and 1H nuclear magnetic resonance. Friction test confirmed that the CS-b-pSBMA copolymer could achieve an excellent lubrication effect on artificial joint materials such as Ti6Al4V alloy with a coefficient of friction as low as 0.008, and on OA-simulated cartilage, better than the conventional lubricant hyaluronic acid, and the adsorption effect of lubricant on cartilage surface was proved by a fluorescence labeling experiment. In addition, CS-b-pSBMA lubricant possessed an outstanding stability, which can withstand enzymatic degradation and even a long-term storage up to 4 weeks. In vitro studies showed that CS-b-pSBMA lubricant had a favorable antibacterial activity and good biocompatibility. In vivo studies confirmed that the CS-b-pSBMA lubricant was stable and could alleviate the degradation process of cartilage in OA mice. This biomimetic lubricant is a promising articular joint lubricant for the treatment of OA and cartilage restoration.

Multifunctional hydrogel coatings with high antimicrobial loading efficiency and pH-responsive properties for urinary catheter applications.

Catheter-associated urinary tract infections are one of the most common hospital-acquired infections. Encrustation formation results from infection of urease-producing bacteria and further complicates the situation. A typical sign of the initial onset of encrustation formation is the alkalization of the urine (pH up to 9-10). However, effective antibacterial strategies with high antimicrobial loading efficiency and pH-responsiveness of antimicrobial release are still lacking. In this study, we developed a poly(sulfobetaine methacrylate)-tannic acid (polySBMA-TA) hydrogel coating, which served as a universal, efficient, and responsive carrier for antimicrobials on urinary catheters. Common antimicrobials, including poly(vinylpyrrolidone)-iodine, copper ions, and nitrofurazone were loaded into the polySBMA-TA coating in high efficiency (several fold higher than that of the polySBMA coating), via the formation of multiple non-covalent interactions between the antimicrobials and hydrogel coating. The hydrogel coatings maintained good antibacterial properties under neutral conditions. More importantly, the pH-responsive release of antibacterial agents under alkaline conditions further enhanced the antibacterial activity of the coatings, which was advantageous for killing the urease-producing bacteria and preventing encrustation. In vitro and in vivo tests confirmed that the hydrogel coating has good biocompatibility, and could effectively inhibit bacterial colonization and encrustation formation. This study offers new opportunities for the utilization of a simple and universal antimicrobial-loaded hydrogel coating with smart pH-responsive properties to combat bacterial colonization and encrustation formation in urinary catheters.

Biomimetic Gradient Hydrogels with High Toughness and Antibacterial Properties.

Traditional hydrogels, as wound dressings, usually exhibit poor mechanical strength and slow drug release performance in clinical biomedical applications. Although various strategies have been investigated to address the above issues, it remains a challenge to develop a simple method for preparing hydrogels with both toughness and controlled drug release performance. In this study, a tannic acid-reinforced poly (sulfobetaine methacrylate) (TAPS) hydrogel was fabricated via free radical polymerization, and the TAPS hydrogel was subjected to a simple electrophoresis process to obtain the hydrogels with a gradient distribution of copper ions. These gradient hydrogels showed tunable mechanical properties by changing the electrophoresis time. When the electrophoresis time reached 15 min, the hydrogel had a tensile strength of 368.14 kPa, a tensile modulus of 16.17 kPa, and a compressive strength of 42.77 MPa. It could be loaded at 50% compressive strain and then unloaded for up to 70 cycles and maintained a constant compressive stress of 1.50 MPa. The controlled release of copper from different sides of the gradient hydrogels was observed. After 6 h of incubation, the hydrogel exhibited a strong bactericidal effect on Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, with low toxicity to NIH/3T3 fibroblasts. The high toughness, controlled release of copper, and enhanced antimicrobial properties of the gradient hydrogels make them excellent candidates for wound dressings in biomedical applications.

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.