Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections.

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Water-Triggered Segment Orientation of Long-Lasting Anti-Biofouling Polyurethane Coatings on Biomedical Catheters via Solvent Exchange Strategy.

The formation of biofilm and thrombus on medical catheters poses a significant life-threatening concern. Hydrophilic anti-biofouling coatings upon catheter surfaces with complex shapes and narrow lumens are demonstrated to have the potential in reducing complications. However, their effectiveness is constrained by poor mechanical stability and weak substrate adhesion. Herein, a novel zwitterionic polyurethane (SUPU) with strong mechanical stability and long-term anti-biofouling is developed by controlling the ratio of sulfobetaine-diol and ureido-pyrimidinone. Once immersed in water, as-synthesized zwitterionic coating (SUPU3 SE) would undergo a water-driven segment reorientation to obtain much higher durability than its direct drying one, even under various extreme treatments, including acidic solution, abrasion, ultrasonication, flushing, and shearing, in PBS at 37 °C for 14 days. Moreover, SUPU3 SE coating could achieve a 97.1% of exceptional reducing protein fouling, complete prevention of cell adhesion, and long-lasting anti-biofilm performance even after 30 days. Finally, the good anti-thrombogenic formations of SUPU3 SE coating with bacterial treatment are validated in blood circulation through an ex vivo rabbit arteriovenous shunt model. This work provides a facile approach to fabricating stable hydrophilic coating through a simple solvent exchange to reduce thrombosis and infection of biomedical catheters.

Protein Desorption Kinetics Depends on the Timescale of Observation.

The presence of so-called reversible and irreversible protein adsorption on solid surfaces is well documented in the literature and represents the basis for the development of nanoparticles and implant materials to control interactions in physiological environments. Here, using a series of complementary single-molecule tracking approaches appropriate for different timescales, we show that protein desorption kinetics is much more complex than the traditional reversible-irreversible binary picture. Instead, we find that the surface residence time distribution of adsorbed proteins transitions from power law to exponential behavior when measured over a large range of timescales (10-2-106 s). A comparison with macroscopic results obtained using a quartz crystal microbalance suggested that macroscopic measurements have generally failed to observe such nonequilibrium phenomena because they are obscured by ensemble-averaging effects. These findings provide new insights into the complex phenomena associated with protein adsorption and desorption.

Highly luminescent, stable, transparent and flexible perovskite quantum dot gels towards light-emitting diodes.

By controlling the hydrolysis of alkoxysilanes, highly luminescent, transparent and flexible perovskite quantum dot (QD) gels were synthesized. The gels could maintain the structure without shrinking and exhibited excellent stability comparing to the QDs in solution. This in situ fabrication can be easily scaled up for large-area/volume gels. The gels integrated the merits of the polymer matrices to avoid the non-uniformity of light output, making it convenient for practical LED applications. Monochrome and white LEDs were fabricated using these QD gels; the LEDs exhibited broader color gamut, demonstrating better property in the backlight display application.

Hierarchical Polymer Brushes with Dominant Antibacterial Mechanisms Switching from Bactericidal to Bacteria Repellent.

Although polycationic surfaces have high antimicrobial efficacies, they suffer from high toxicity to mammalian cells and severe surface accumulation of dead bacteria. For the first time, we propose a surface-initiated photoiniferter-mediated polymerization (SI-PIMP) strategy of constructing a "cleaning" zwitterionic outer layer on a polycationic bactericidal background layer to physically hinder the availability of polycationic moieties for mammalian cells in aqueous service. In dry conditions, the polycationic layer exerts the contact-active bactericidal property toward the adherent bacteria, as the zwitterionic layer collapses. In aqueous environment, the zwitterionic layer forms a hydration layer to significantly inhibit the attachment of planktonic bacteria and the accumulation of dead bacteria, while the polycationic layer kills bacteria occasionally deposited on the surface, thus preserving the antibacterial capability for a long period. More importantly, the zwitterionic hydrated layer protects the mammalian cells from toxicity induced by the bactericidal background layer, and therefore hierarchical antibacterial surfaces present much better biocompatibility than that of the naked cationic references. The dominant antibacterial mechanism of the hierarchical surfaces can switch from the bactericidal efficacy in dry storage to the bacteria repellent capability in aqueous service, showing great advantages in the infection-resistant applications.

A metal-organic framework-integrated composite for piezocatalysis-assisted tumour therapy: design, related mechanisms, and recent advances.

With the growing need for more effective tumour treatment, piezocatalytic therapy has emerged as a promising approach due to its distinctive capacities to generate ROS through stress induction and regulate the hypoxic state of the TME. MOF-based piezocatalysts not only possess the benefits of piezocatalysis but also exhibit several advantages associated with MOFs, such as tunable pore size, large specific surface area, and good biocompatibility. Therefore, they are expected to become a powerful promoter of piezocatalytic therapy. This review elaborates on the fundamental principles of piezocatalysis and summarises recent advances in the piezocatalytic therapy and combination therapies of tumours, generalising the strategies for constructing piezocatalytic systems based on MOFs. Finally, the challenges confronted and future opportunities for the design and application of piezocatalytic MOF anticancer systems have been discussed.

Biological applications of lipoic acid-based polymers: an old material with new promise.

Lipoic acid (LA) is a versatile antioxidant that has been used in the treatment of various oxidation-reduction diseases over the past 70 years. Owing to its large five-membered ring tension, the dynamic disulfide bond of LA is highly active, enabling the formation of poly(lipoic acid) (PLA) via ring-opening polymerization (ROP). Herein, we first summarize disulfide-mediated ROP polymerization strategies, providing basic routes for designing and preparing PLA-based materials. PLA, as a biologically derived, low toxic, and easily modified material, possesses dynamic disulfide bonds and universal non-covalent carboxyl groups. We also shed light on the biomedical applications of PLA-based materials based on their biological and structural features and further divide recent works into six categories: antibacterial, anti-inflammation, anticancer, adhesive, flexible electronics, and 3D-printed tissue scaffolds. Finally, the challenges and future prospects associated with the biomedical applications of PLA are discussed.

Metal-organic framework-based platforms for implantation applications: recent advances and challenges.

The development of minimally invasive technology has promoted the widespread use of implant interventional materials, which play an important role in alleviating patients' pain during and after surgery. Metal-organic frameworks (MOFs) and their related hybrids formed by bridging ligands and metal nodes via covalent bonds represent one of the smart platforms in implant interventional fields due to their large surface area, adjustable compositions and structures, biodegradability, etc. Significant progresses in the implantation application of MOF-based materials have been achieved recently, but these studies are still in the initial stage. This review highlights the recent advances of MOFs and their related hybrids in orthopedic implantation, cardio-vascular implantation, neural tissue engineering, and biochemical sensing. Each correction between the structural features of MOFs and their corresponding implanted works is highlighted. Finally, the confronting challenges and future perspectives in the implant interventional field are discussed.

Heparin-network-mediated long-lasting coatings on intravascular catheters for adaptive antithrombosis and antibacterial infection.

Bacteria-associated infections and thrombosis, particularly catheter-related bloodstream infections and catheter-related thrombosis, are life-threatening complications. Herein, we utilize a concise assembly of heparin sodium with organosilicon quaternary ammonium surfactant to fabricate a multifunctional coating complex. In contrast to conventional one-time coatings, the complex attaches to medical devices with arbitrary shapes and compositions through a facile dipping process and further forms robust coatings to treat catheter-related bloodstream infections and thrombosis simultaneously. Through their robustness and adaptively dissociation, coatings not only exhibit good stability under extreme conditions but also significantly reduce thrombus adhesion by 60%, and shows broad-spectrum antibacterial activity ( > 97%) in vitro and in vivo. Furthermore, an ex vivo rabbit model verifies that the coated catheter has the potential to prevent catheter-related bacteremia during implantation. This substrate-independent and portable long-lasting multifunctional coating can be employed to meet the increasing clinical demands for combating catheter-related bloodstream infections and thrombosis.

Regulable Polyelectrolyte-Surfactant Complex for Antibacterial Biomedical Catheter Coating via a Readily Scalable Route.

Constructing multifunctional surfaces is one of the practical approaches to address catheter-related multiple complications but is generally time-consuming and substrate-dependent. Herein, a novel anti-adhesion, antibacterial, low friction, and robustness coating on medical catheters are developed via a universal and readily scalable method based on a regulable polyelectrolyte surfactant complex. The complex is rapidly assembled in one step by electrostatic and hydrophobic interactions between organosilicon quaternary ammonium surfactant (N+ Si ) and adjustable polyelectrolyte with cross-linkable, anti-adhesive, and anionic groups. The alcohol-soluble feature of the complex is conducive to the rapid formation of coatings on any medical device with arbitrary shapes via dip coating. Different from the conventional polyelectrolyte-surfactant complex coating, the regulated complex coating with nonleaching mode could be stable in harsh conditions (high concentration salt solution, organic reagents, etc.) because of the cross-linked structure while improving the biocompatibility and reducing the adhesion of various bacteria, proteins, and blood cells. The coated catheter exhibits good antibacterial infection in vitro and in vivo, owing to the synergistic effect of N+ Si and zwitterionic groups. Therefore, the rationally designed complex supplies a facile coating approach for the potential development in combating multiple complications of the medical catheter.

Salt-Triggered Adaptive Dissociation Coating with Dual Effect of Antibacteria and Anti-Multiple Encrustations in Urological Devices.

Bacterial infections and multiple encrustations are life-threatening complications in patients implanted with urological devices. Limited by time-consuming procedures and substrate dependence, it is difficult to simultaneously prevent the aforementioned complications. Herein, is reported the design of a salt-triggered chondroitin sulfate complex (CS/Si-N+ ) coating with adaptive dissociation, which realizes the dual functions of antibacterial and anti-multiple encrustations in urological devices with arbitrary shapes. The existence of covalent interactions between the complex and the interface ensures the formation of a robust coating, especially in harsh environments. Benefiting from the adaptive dissociation of the ion pairs in the CS/Si-N+ coating in urine electrolytes, the exposed ion groups and enhanced hydrophilicity are more conducive to the inhibition of bacterial infection and multiple encrustations simultaneously. The coating exhibits broad-spectrum bactericidal effects. As a proof of concept, in a simulated metabolic encrustation model, the coating exhibits significant advantages in resisting calcium oxalate encrustation, with a reduction in the calcium content by over 90%. In addition, this non-leachable all-in-one coating shows good biocompatibility in a pig in vivo model. Such a coating strategy is expected to be a practical approach for preventing urological medical device-related complications.

Mussel-inspired polysaccharide-based sponges for hemostasis and bacteria infected wound healing.

Effective bleeding control and wound protecting from infection play critical roles in the tissue healing process. However, local hemostats are not involved in the whole healing processes to promote the final healing efficiency. Here, a multi-functional mussel-inspired polysaccharide-based sponge with hemostatic, antibacterial and adhesive properties was fabricated via cryopolymerization of oxidized dextran (OD), carboxymethyl chitosan (CC) and polydopamine nanoparticles (PDA-NPs), followed by lyophilization. Combining with the adsorbed thrombin, the sponges yielded a considerably lower amount of blood than the commercially available hemostatic dressings. Benefiting from the high photo-thermal transition efficiency of PDA-NPs, the sponges exhibited excellent antibacterial activity to both gram positive and negative bacteria. Owing to the rapid hemostatic activity and effective infection resistance, the sponges illustrated the significantly acceleratory wound healing efficiency compared with the control group. The thrombin-loaded OD/CC-PDA polysaccharide-based sponge has great potential for future clinical use as wound dressing.

Correction: The recent advances in surface antibacterial strategies for biomedical catheters.

Correction for 'The recent advances in surface antibacterial strategies for biomedical catheters' by Lin Liu et al., Biomater. Sci., 2020, DOI: 10.1039/d0bm00659a.

The recent advances in surface antibacterial strategies for biomedical catheters.

As one of the most common hospital-acquired infections, catheter-related infections (CRIs) which are caused by microbial colonization lead to increasing morbidity and mortality of patients and life threat for medical staffs. In this case, a variety of efforts have been made to design functional materials to limit bacterial colonization and biofilm formation. In this review, we focus on the recent advances in surface modification strategies of biomedical catheters used to prevent CRIs. The tests for the evaluation of the performances of modified catheters are listed. Future prospects of surface antibacterial strategies for biomedical catheters are also outlined.

Surface-Adaptive and On-Demand Antibacterial Sponge for Synergistic Rapid Hemostasis and Wound Disinfection.

Uncontrolled hemorrhage is the leading factor causing death in military trauma and clinical practice and is usually accompanied with bacterial infection. The fabrication of a functional hemostatic sponge for combating bacteria is of vital importance. Poly(hexamethylene biguanide) hydrochloride (PHMB) has been shown to have a remarkable bactericide effect. However, PHMB after use might have a toxic effect on humans. Herein, a powerful surface-adaptive, on-demand antibacterial hemostatic sodium alginate/gelatin sponge is fabricated by sequential spray-assisted layer-by-layer assembly of PHMB and hyaluronic acid (HA). The HA upper layer could endow the coating surface with better biocompatibility under physiological conditions. Once bacteria invade, the secreted hyaluronidase could degrade the upper HA layer, and then the exposed PHMB layer could kill the bacteria. The coated sponge shows excellent biocompatibility, as negatively charged HA can prevent the exposure of bactericidal PHMB. Moreover, the coated sponge exhibited excellent hemostatic properties in vitro and in vivo by aggregating and activating blood cells. Our strategy provides a novel approach to the design of surface-adaptive and on-demand bactericidal coatings on the surface of hemostatic sponges, which has the advantage of avoiding infection complications during hemostasis.

One-step hydrophobization of tannic acid for antibacterial coating on catheters to prevent catheter-associated infections.

Catheter-associated infections (CAIs) caused by bacterial colonization are significant problems in clinics. Thus, effective antibacterial coatings for biomedical catheters to prevent bacterial infections are urgently needed. Ideal coatings should include the advantage of potent antibacterial properties and being easily and economically modified on the catheter surface. Due to their advantages of adhesive capability on various substrates, an increasing number of coatings based on plant polyphenols have been developed. However, the hydrophilicity of plant polyphenols limits their utilization in coatings. Herein, hydrophobic tannic acid (TA) was synthesized via the one-step electrostatic assembly of TA and benzalkonium chloride (BAC) with the green solvent water as the medium. The as-prepared hydrophobic TA (TBA) facilely formed a stable and colorless coating on the luminal and outer surface of biomedical catheters with broad-spectrum antibacterial activity and biocompatiblity. It was demonstrated that the TBA-coated surfaces displayed excellent bactericidal activity toward Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and more than 99% of the above bacteria were killed by the TBA-coated films. The test of the coated catheters in vitro also showed the excellent antibacterial activity of both the outer and luminal surfaces of the catheter. Moreover, in an in vivo mouse model, the coated catheters relatively prevented bacterial colonization compared to the uncoated catheters. Meantime, no significant cytotoxicity and host response for Cell Counting Kit-8 (CCK-8) and tissue compatibility in vivo were observed, indicating the better biocompatibility of the TBA coating. This preparation method overcomes the limitation of the traditional hydrophilic tannic acid as a coating and provides a new method for preventing medical indwelling device-associated infections.

Two-dimensional polymers with versatile functionalities via gemini monomers.

Two-dimensional synthetic polymers (2DSPs) are sheet-like macromolecules consisting of covalently linked repeat units in two directions. Access to 2DSPs with controlled size and shape and diverse functionality has been limited because of the need for monomers to retain their crystallinity throughout polymerization. Here, we describe a synthetic strategy for 2DSPs that obviates the need for crystallinity, via the free radical copolymerization of amphiphilic gemini monomers and their monomeric derivatives arranged in a bilayer at solid-liquid interfaces. The ease of this strategy allowed the preparation of 2DSPs with well-controlled size and shape and diverse functionality on solid templates composed of various materials with wide-ranging surface curvatures and dimensions. The resulting 2DSPs showed remarkable mechanical strength and have multiple applications, such as nanolithographic resist and antibacterial agent. The broad scope of this approach markedly expands the chemistry, morphology, and functionality of 2DSPs accessible for practical applications.

Development of hierarchical Fe3O4 magnetic microspheres as solid substrates for high sensitive immunoassays.

Improving the detection sensitivity of enzyme linked immunosorbent assay (ELISA) is of the utmost importance for meeting the demand of early disease diagnosis. In this work, a sensitive solid substrate for ELISA, i.e., hierarchical iron oxide magnetic microspheres, Fe3O4@mSiO2@poly[poly(ethylene glycol) methacrylate-co-glycidyl methacrylate], was developed via a novel surface-initiated photoiniferter-mediated polymerization (SI-PIMP) strategy. The magnetic microspheres consist of a magnetic Fe3O4 core that gives a high magnetic response, a 3D backbone, a mesoporous SiO2 middle layer, that facilitates microsphere stability and provides anchoring sites, and polymer brushes, that serve as an antifouling and oriented antibody immobilization layer. As a result, the as-prepared microspheres possess a high antibody loading capacity, an enhanced detection signal and a dramatically improved sensitivity, resulting in a 25-fold improvement over conventional ELISA solid substrates.

Water-Insoluble Polymeric Guanidine Derivative and Application in the Preparation of Antibacterial Coating of Catheter.

Antibacterial coatings have been considered as an effective method for preventing the implant-associated infections caused by the bacterial colonization. In this study, we report a water-insoluble polyelectrolyte-surfactant complex, poly(hexamethylene biguanide) hydrochloride-sodium stearate (PHMB-SS) that can be facilely coated onto the surfaces of biomedical catheter and kill the bacteria by releasing the PHMB and prevent the generation of the biofilm. The PHMB-SS-coated surfaces showed better bactericidal activity toward Staphylococcus aureus and Escherichia coli. The PHMB-SS-coated catheters could not only relatively prevent the bacterial colonization in vitro but also in an implant-associated bacterial infection animal model in vivo. Moreover, no significant cytotoxicity and host response were observed in vitro and in vivo, indicating the high biocompatibility of the coating. The water-insoluble antibacterial coating reported in this work represents a novel approach to build a simple and effective coating for the prevention of device-associated infections.

Cell-inspired biointerfaces constructed from patterned smart hydrogels for immunoassays in whole blood.

Immunoassays have shown great advances in the fields of biomedical diagnosis. However, successful immunoassays in blood plasma or whole blood based on the designed biointerfaces are still rare. Here, a newly cell-inspired biointerface for immunoassays in blood is demonstrated. Inspired by the high resistance to protein and cell adhesion and extraordinary biological recognition of stem cells, the biointerfaces are constructed by patterning smart hydrogels (PNIPAAm-co-PNaAc) on hydrophilic layers (PEG), followed by immobilization of antibodies on the patterned hydrogels. The hierarchical biointerfaces are hydrophilic to resist blood plasma and blood cell adhesion, but exhibit high affinity to the target antigens. As a result, successful immunoassays in blood are achieved. In addition, the detection signal is further enhanced by the manipulation of the phase transition of the smart hydrogels with temperature, and the sensitivity is higher than that of the widely-used poly(acrylic acid)/(polyacrylate) platform. The biointerface is versatile and effective in antibody-antigen recognition, which offers a potential new approach for developing highly sensitive immunoassays in blood.