Fabrication of antimicrobial cationic hydrogels driven by physically and chemically crosslinking for wound healing.

The wound therapy based on antibiotic delivery inevitably leads to the emergence of drug resistance. Hydrogel biomaterials with inherent antibacterial activities have emerged as promising candidates for addressing this issue. However, developing an inherently antibacterial hydrogel through simple and facile strategies to promote localized wound infection healing remains a challenge. In this study, we successfully constructed antimicrobial cationic hydrogels with self-healing and injectable properties through physically and chemically dual-crosslinked networks. The networks were formed by the copolymers poly[(di(ethylene glycol) methyl ether methacrylate)-co-(4-formylphenyl methacrylate)-co-(2-(methacryloyloxy)ethyl]trimethylammonium chloride solution)] (PDFM) and poly[(di(ethylene glycol) methyl ether methacrylate)-co-(2-aminoethyl methacrylate hydrochloride)-co-(2-(((6-(6-methyl-4[1H]pyrimidionylureido) hexyl)carbamoyl)oxy)ethyl methacrylate)] (PDAU). The hydrogel systems effectively facilitate the regeneration and healing of infected wounds through the contact bactericidal feature of quaternary ammonium cations. The presence of Schiff base bonds in the injectable hydrogels imparts remarkable pH responsiveness and self-healing properties. In vitro experiments verified their intrinsic antibacterial activities along with their favorable cytocompatibility and hemocompatibility in both in vitro and in vivo. In addition, the hydrogel significantly accelerated the healing of bacterially infected in a full-thickness skin wound. This facilely prepared dual-crosslinked hydrogel, without antibiotics loading, holds significant prospects for treating infected wounds.

Codelivery of CuS and DOX into Deep Tumors with Size and Charge-Switchable PAMAM Dendrimers for Chemo-photothermal Therapy.

Accurate targeting of therapeutic agents to specific tumor tissues, especially via deep tumor penetration, has been an effective strategy in cancer treatments. Here, we described a flexible nanoplatform, pH-responsive zwitterionic acylsulfonamide betaine-functionalized fourth-generation PAMAM dendrimers (G4-AB), which presented multiple advantages for chemo-photothermal therapy, including template synthesis of ultrasmall copper sulfide (CuS) nanoparticles and further encapsulation of doxorubicin (DOX) (G4-AB-DOX/CuS), long-circulating performance by a relatively large size and zwitterionic surface in a physiological environment, combined size shrinkage, and charge conversions via pH-responsive behavior in an acidic tumor microenvironment (TME). Accordingly, high tumor penetration and positive cell uptake for CuS and DOX have been determined, which triggered an excellent combination treatment under near-infrared irradiation in comparison to the monochemotherapy system and irresponsive chemo-photothermal system. Our study represented great promise in constructing multifunctional carriers for the effective delivery of photothermal nanoparticles and drugs in chemo-photothermal therapy.

Highly Stretchable, Self-Healing, Injectable and pH Responsive Hydrogel from Multiple Hydrogen Bonding and Boron-Carbohydrate Interactions.

A simple and cost-effective method for the fabrication of a safe, dual-responsive, highly stretchable, self-healing and injectable hydrogel is reported based on a combination of dynamic boronate ester bonds and hydrogen bonding interactions. The mechanical properties of the hydrogel are tunable by adjusting the molar ratios between sugar moieties on the polymer and borax. It was remarkable to note that the 2:1 ratio of sugar and borate ion significantly improves the mechanical strength of the hydrogel. The injectability, self-healing and stretchability properties of the hydrogel were also examined. In addition, the impact of the variation of the pH and the addition of free sugar responsiveness of the hydrogel was studied. High MRC-5 cell viability was noticed by the 3D live/dead assay after 24 h cell culture within the hydrogel scaffold. Hence, the developed hydrogels have desirable features that warrant their applications for drug delivery, scaffolds for cell and tissue engineering.

Glycopolymer-based multifunctional antibacterial hydrogel dressings for accelerating cutaneous wound healing.

Antimicrobial hydrogel dressings have received extensive attention for their wide and promising applications in preventing infections associated with wound healing. However, the development of versatile antibacterial hydrogels inevitably leads to complex structures, which restricts their applications. In this work, a multifunctional antibacterial hydrogel based on a reversible diolborate bond crosslinked network was prepared via the interactions between the zwitterionic glycopolymer poly[(2-methacryloyloxyethyl phosphorylcholine)-co-(N,N-dimethylacrylamide)-co-(2-lactobionamidoethyl methacrylamide)] (PMDL) and borax in conjunction with a simple mixing of Ag NPs within 10 s. The obtained PMDL-12%/borax/Ag NP hydrogel displays a rapid self-healing ability and excellent injectability, as well as good adhesiveness to biological tissues and surfaces of various materials. Moreover, the hydrogels exhibit efficient antibacterial activities against Escherichia coli and Staphylococcus aureus, which could prevent bacterial infections in wound care. The multifunctional hydrogel also shows good cytocompatibility and hemocompatibility. Importantly, in vivo wound healing evaluation of a mouse full-thickness skin defect model confirms that the hydrogel effectively accelerates cutaneous regeneration and wound healing by regulating inflammation and promoting collagen deposition. This multifunctional wound dressing hydrogel prepared using a facile strategy has promising application in biomedical areas.

Synthesis of pH-responsive polyzwitterions for activated cellular uptake and tumor accumulation of gold nanoparticles at tumorous acidity.

The response sensitivity of surface material plays an important role in adjustable nano-bio interactionin vivo. In this present, a zwitterionic polymer (polyzwitterion) containing quaternary ammonium cation and sulfonamide anion poly(4-((4-(3-(methacryloyloxy)propoxy)phenyl) sulfonamido)-N, N, N-trimethyl-4-oxobutan-1-aminium chloride) (PMPTSA) was synthesized by Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization to explore the pH responsive behavior in tumors. The PMPTSA-coated gold nanoparticles (PMPTSA-@-Au NPs) showed zwitterionic nature such as antifouling ability, low cellular uptake and prolonged circulation time similar with common hydrophilic polymers, including polyethylene glycol (PEG), poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate) functional gold nanoparticles in physiological environment (pH 7.4). A high sensitivity and reversible positive charge conversion of P(MPTSA)-@-Au NPs at tumor slight acidic microenvironment (∼pH 6.8) leaded to an enhanced cellular internalization than that at pH 7.4 and increased tumor accumulation compared with PEG, polycarboxybetaines and polymer sulphobetaine (PSB) functional gold nanoparticles. The highly pH responsive PMPTSA will provide the promising application in cancer nanomedicine.

Synergistic size and charge conversions of functionalized PAMAM dendrimers under the acidic tumor microenvironment.

Developing nanomedicine with highly adaptive behaviors has shown great effectiveness in cancer treatment. However, the multi-functional integration of nano-therapeutic systems inevitably leads to complexity in the structure and impairs the operational efficiency or performance. Herein, we describe a novel nano-therapeutic system, G4-AB, capable of simultaneous dual conversions of the size and charge while targeting the acidic tumor microenvironment. G4-AB, containing a hydrophobic inner cavity for doxorubicin (DOX) loading, was synthesized by modifying amine-terminated 4th-generation polyamidoamine (G4-PAMAM) dendrimers with acylsulfonamide betaine (AB). Due to the dipole-dipole interaction among the AB moieties, G4-AB self-assembles to form micellar clusters with a zwitterionic surface. Possessing an anti-fouling property and suitable size, G4-AB exhibits optimized blood circulation under physiological pH conditions. Moreover, the extracellular pH value of the tumor microenvironment (pH 6.5) can trigger the protonation of acylsulfonamide, resulting in the cationization of AB and dissociation of G4-AB into unimolecular micelles (∼12 nm) due to electrostatic repulsion. The synergistic dual conversions further ensure drug accumulation with enhanced tumor penetration and cell internalization. The in vitro and in vivo experiments demonstrate that the G4-AB-DOX nano-therapeutic system possesses better antitumor efficiency and lower toxicity than free DOX or PEGylated PAMAM.

Dopamine Assisted Self-Cleaning, Antifouling, and Antibacterial Coating via Dynamic Covalent Interactions.

The rapid accumulation of dead bacteria or protein on a bactericidal surface can reduce the effectiveness of the modified surface and alter its biocidal activity by shielding the surface biocide functional groups, promoting microbial attachment and subsequent biofilm formation. Thus, the alteration of biocidal activity due to biofilm formation can cause serious trouble including severe infection or implant or medical device failure leading to death. Therefore, developing a smart self-cleaning surface is of great interest. Ideally, such a surface can not only kill the attached microbials but also release the dead cells and foulants from the surface under a particular incitement on demand. In this project, a sugar-responsive self-cleaning coating has been developed by forming covalent boronic ester bonds between catechol groups from polydopamine and a benzoxaborole pendant from zwitterionic and cationic polymers. To incorporate antifouling properties and enhance the biocompatibility of the coating, bioinspired zwitterionic compound 2-methacryloyloxyethyl phosphorylcholine (MPC) was chosen and benzoxaborole pendant containing zwitterionic polymer poly(MPC-st-MAABO) (MAABO: 5-methacrylamido-1,2-benzoxaborole) was synthesized. Additionally to impart antibacterial properties to the surface, a quaternary ammonium containing cationic polymer poly(2-(methacryloyloxy)ethyl trimethylammonium (META)-st-MAABO)) was synthesized. These synthesized polymers were covalently grafted to a polydopamine (PDA) coated surface by forming a strong cyclic boronic ester complex with a catechol group of the PDA layer endowing the surface with bacteria contact-killing properties and capturing specific protein. After the addition of cis-diol containing competitive molecules, i.e., saccharides/sugars, this boronic ester complex with a catechol group of PDA was replaced and the attached polymer layer was cleaved from the surface, resulting in the release of both absorbed protein and live/killed bacteria electrostatically attached to the polymer layer. This dynamic self-cleaning surface can be a promising material for biomedical applications avoiding the gathering of dead cells and debris that are typically encountered on a traditional biocidal surface.

Construction of antibacterial adhesion surfaces based on bioinspired borneol-containing glycopolymers.

Preparation of antibacterial coating materials is considered an effective strategy to prevent medical device-related infections. In the present study, by combining 2-lactobionamidoethyl methacrylamide with a uniquely structured borneol compound, new copolymers poly(2-lactobionamidoethyl methacrylamide-co-glycidyl methacrylate-co-isobornyl acrylate) (poly(LAEMA-co-GMA-co-BA)) were synthesized by a simple free-radical polymerization. An amine containing silane layer was first prepared on the substrate surface by a silanization reaction. The glycopolymers were grafted onto the silane layer through covalent bonding to obtain glycosylated coatings. X-ray photoelectron spectroscopy (XPS) confirmed the successful preparation of the APTES-functionalized surface and polymer layers. The surface wettability was measured by the contact angle (CA). The coated surfaces were relatively flat and smooth as confirmed by Atomic Force Microscopy (AFM). Moreover, the prepared coatings showed good antibacterial adhesion properties toward both E. coli and S. aureus. Furthermore, no significant cytotoxicity to the MRC-5 cells (lung fibroblasts) in vitro was observed, indicating the good biocompatibility of the antibacterial coatings. This study provides an excellent strategy for designing an antibacterial surface containing glycopolymers and natural antibacterial compounds, and these coatings may be suitable for medical devices.

Dual Cross-Linked Hydrogels with Injectable, Self-Healing, and Antibacterial Properties Based on the Chemical and Physical Cross-Linking.

Injectable hydrogels have become a promising material for biomedical engineering applications, but microbial infection remains a common challenge in their application. In this study, we presented an injectable antibacterial hydrogel with self-healing property based on a dual cross-linking network structure of dynamic benzoxaborole-sugar and quadruple hydrogen bonds of the 2-ureido-4-pyrimidone (UPy) moieties at physiological pH. Dynamic rheological experiments demonstrated the gelatinous behavior of the double cross-linking network (storage modulus G' > loss modulus G″), and the modulus showed frequency-dependent behavior. The noncovalent interactions of UPy units in the polymer segment endowed the injectable hydrogels with good mechanical strength. By varying the solid contents, UPy units, as well as the pH, the mechanical properties of hydrogels could be controlled. Additionally, the hydrogels exhibited not only excellent self-healing and injectable properties but also pH and sugar dual-responsiveness. Moreover, the hydrogels could effectively inhibit the growth of both Escherichia coli and Staphylococcus aureus while exhibiting low toxicity. 3D cell encapsulation experiment results also demonstrated the potential use of these hydrogels as cell culture scaffolds. Taken together, the injectability, self-healing, and antimicrobial properties of the prepared hydrogels showed great promise for translational medicine, such as cell and tissue engineering applications.

Antifouling and Antibacterial Polymer-Coated Surfaces Based on the Combined Effect of Zwitterions and the Natural Borneol.

The development and application of natural antibacterial materials have always been the focus of biomedical research. Borneol as a natural antibacterial compound has received extensive attention. However, the hydrophobicity caused by its unique structure limits its application range to a certain extent. In this study, we combine zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) with a complex bicyclic monoterpene structure borneol compound and prepare an excellent antifouling and antibacterial surface via the Schiff-base bond. The prepared coating has excellent hydrophilicity verified by the contact angle (CA), and its polymer layer is confirmed by X-ray photoelectron spectroscopy (XPS). The zwitterion MPC and borneol moieties in the copolymer play a coordinating role, relying on super hydration and the special stereochemical structure to prevent protein adsorption and inhibit bacterial adhesion, respectively, which are demonstrated by bovine serum albumin (BSA) adsorption and antibacterial activity test. Moreover, the water-soluble borneol derivative as the antibacterial surfaces we designed here was biocompatible toward MRC-5 (lung fibroblasts), as showed by in vitro cytotoxicity assays. Such results indicate the potential application of the as-prepared hydrophilic surfaces in the biomedical materials.

Construction and properties of the antibacterial epitaxial transition layer on a zirconia ceramic surface.

Secondary caries is one of the main causes of dental zirconia restoration failure in the clinic. Therefore, it is urgent to improve the antibacterial performance of zirconia ceramics to reduce the occurrence of secondary caries. In this study, a quaternary ammonium compound antibacterial polymer was innovatively synthesized by solution polymerization with a quaternary ammonium salt monomer as the antibacterial component. The antibacterial epitaxial transition layer was successfully prepared on the surface of zirconia ceramics by the hydroxyl group on HEMA reacting with the siloxane group in the KH570 hydrolysate, which makes the antibacterial polymer indirectly chemically combine with the silicate epitaxial transition layer. The antibacterial epitaxial transition layer exhibited excellent mechanical properties, satisfactory biocompatibility and significant antibacterial effects, and the maximum antibacterial rate is 99%. The antibacterial epitaxial transition layer plays an important role in preventing secondary caries and improving the success rate of clinical zirconia ceramic restorations.

Synthesis, characterization, and aging resistance of the polyurethane dimethacrylate layer for dental restorations.

In this study, polyurethane dimethacrylate (PUDMA) was synthetized from different components and incorporated into a direct resin composite restoration system with the aim to buffer tooth-resin interfacial stresses and maintain the marginal adaptation. The tensile strength, elongation at fracture (ε), and thermal stability of the PUDMA layer were characterized, showing a tensile strength of 22 MPa, an ε of 112%, and a thermal decomposition temperature of about 282°C. In addition, the degree of conversion, water sorption/solubility, hydrophobicity, microtensile bond strength (µTBS), marginal leakage, and cytotoxicity in vitro were evaluated for the PUDMA layer. The data were analyzed using one-way ANOVA, except for leakage depths (which were analyzed using the Wilcoxon paired-rank test). The level of significance was set at 0.05. Compared with dental adhesives, PUDMA displayed a higher degree of conversion, lower water sorption/solubility, and improved hydrophobicity and biocompatibility in vitro. After thermocycling, the µTBS of the restoration system containing PUDMA had increased compared with the µTBS at 24 h. Restorations containing PUDMA showed lower leakage depths than those which did not contain PUDMA. In conclusion, because of its hydrophobic and elastic nature, the PUDMA layer, when used as an intermediate between tooth and resin restoratives, may buffer interfacial stresses, improve the stability and durability of the bonding interface, and reduce microleakage.

The functions of hydrophobic elastic polyurethane combined with an antibacterial triclosan derivative in the dentin restoration interface.

Dentin restoration produces weak interfaces because of the effects of bacterial microflora, biofilms, and mechanical, thermal, and shrinkage stresses. This results in secondary caries. Therefore, hydrophobic elastic polyurethane (PU) containing different concentrations of triclosan derivatives was synthesized and applied to solve this problem. The antibacterial PU was characterized according to its tensile strength (TS) and elasticity (ε) via a universal testing machine, and water sorption (Wsp) and solubility testing (Wsl) was performed according to ISO 4049: 2009. Additionally, this study evaluated the antibacterial properties of PU against Streptococcus mutans (ATCC35668) and Escherichia coli (ATCC25922). A marginal leakage test was performed to evaluate the leakage prevention property. As a result, the antibacterial PU showed high TS (>17 MPa), high elasticity (ε > 65%), and low Wsp (>81.06 µg/mm3) and Wsl (>11.22 µg/mm3). The PU exhibited antibacterial effects against both Streptococcus mutans and Escherichia coli. The antibacterial rates were over 90% and >99% for the 3% and 5% groups, respectively. Moreover, the marginal level of leakage was 0. Based on the mechanical properties, Wsp and Wsl values and the antibacterial properties, the 3% group exhibited satisfactory performance and has been deemed a possible solution to reduce the occurrence of secondary caries.

Fabrication of Robust Antibacterial Coatings Based on an Organic-Inorganic Hybrid System.

Antibacterial coatings have drawn much attention because of their high potential applications in medicine. However, the weak mechanical property, poor biosafety, and biocompatibility of most established antibacterial coatings restrict their applications. In this study, robust antibacterial coatings were fabricated via a simple organic-inorganic hybrid method. The polymer component provides an excellent antibacterial property to the coatings, and the hybrid silica sol improves the hardness of coatings. After cross-linking, network-structured coatings were formed. The coating surfaces exhibited high transmittance, excellent mechanical property, and good antibacterial effect against Escherichia coli (Gram-negative) and Streptococcus mutans (Gram-positive). Additionally, the robust coatings were noncytotoxic with satisfactory biocompatibility. Such results provide a theoretical basis for their applications in the biomedical field.

Superhydrophobic coatings with self-cleaning and antibacterial adhesion properties for denture base.

In this paper, coatings with antibacterial adhesion, excellent biocompatibility, good superhydrophobicity and highly transmittance were fabricated by mixing hydroxyl group fluropolymer (PHF), polyurethane oligomer (Pre-PU) with epoxy functionalized SiO2 nanoparticles and thermal-crosslinked. The properties of coatings were investigated by Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM), Atomic force microscopy (AFM), Ultraviolet near-infrared visible spectrophotometer (UV-3600). The morphology results indicated that the roughness scale of micro-nano structure surface can be monitored by changing the contents of functionalized polymers and SiO2. The coating S2 showed outstanding superhydrophobicity with the contact angle of 155.9°, the sliding angle less than 1°, and good transparency. Furthermore, the coating exhibited antibacterial adhesion and favorable biosafety, confirming a potential for application in the oral field.

Aliphatic amine responsive organogel system based on a simple naphthalimide derivative.

A new gelator 1 based on a simple naphthalimide derivative was synthesized and fully characterized. It was found that the organogel 1 was formed only in a mixed solvent of methanol and H2O (1/1, v/v). The organogel was thoroughly characterized by using various microscopic techniques including field-emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), and UV-vis, fluorescence and Fourier transform infrared (FTIR) spectroscopy. Hydrogen bonds were the main driving force for the organogel formation. Interestingly, the organogel 1 exhibited the ability to distinguish aliphatic amines from aromatic amines. The gel state and fluorescence emission intensity were both changed after two minutes after the addition of aliphatic amines. This organogel system could be applied in the detection of aliphatic amine pollutants.