Mucoadhesive, antioxidant, and lubricant catechol-functionalized poly(phosphobetaine) as biomaterial nanotherapeutics for treating ocular dryness.

Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.

Betainization of Polydopamine/Polyethylenimine Coating for Universal Zwitterionization.

Biofoulants can adhere to multiple surfaces, degrading the performance of medical devices and industrial facilities and/or causing nosocomial infection. The surface immobilization of zwitterionic materials can prevent the initial attachment of the foulants but lacks extensive implementation. Herein, we propose a facile, universal, two-step surface modification strategy to improve fouling resistance. In the first step, the substrates were immersed in a codeposition solution containing dopamine and branched polyethylenimine (PEI) to form a "primer" layer (PDA/PEI). In the second step, the primer layers were treated with 1,3-propane sultone to betainize primary/secondary/tertiary amine moieties of PEI, generating zwitterions on substrates. After betainization, PS-grafted PDA/PEI (PDA/PEI/S) via a ring-opening alkylation reaction manifested changes in wettability. X-ray photoelectron spectroscopy revealed the presence of zwitterionic moieties on the PDA/PEI/S surfaces. Further investigations using ellipsometry and atomic force microscopy were conducted to scrutinize the relation among the PEI content, film thickness, primer stability, and betainization. As a result, zwitterion-decorated substrates prepared under optimal conditions can exhibit high resistance against bacterial fouling, achieving a 98.5% reduction in bacterial attachment. In addition, the method shows a substrate-independent property, capable of successfully applying it on organic and inorganic substrates. Finally, the newly developed approach shows excellent biocompatibility, displaying no significant difference compared with blank control samples. Overall, we envision that the facile surface modification strategy can further promote the preparation of zwitterion-decorated materials in the future.

Catechol-functionalized sulfobetaine polymer for uniform zwitterionization via pH transition approach.

The study aims to develop a modification strategy to facilitate uniform catechol-assisted zwitterionization on nitinol alloy for bio-compatibility and fouling resistance. Catechol-functionalized polysulfobetaine methacrylate (pSBMA/DA) is synthesized via dopamine-initiated photo-polymerization. Under UV irradiation, semiquinone radicals from dopamine (DA) can be generated, and prevented loss of one electron to intramolecular cyclization and intermolecular dimerization in a solution at pH 2. Pseudo-first-order polymerization kinetics, and relations of apparent rate constant and number average molecular weight with the molar ratio of DA in photopolymerization for pSBMA/DA are unveiled. In a solution at pH 3, PSBMA/DA begins aggregation, kept catechol moieties from premature oxidization, and enabled even deposition on the nitinol substrate. After pH regulation to 8.5, pSBMA/DA extends, and concurrently catechol moieties are activated to interact with the nitinol surface via the formation of bidentate binding. X-ray photoelectron spectroscopy (XPS) analysis revealed that a shorter pSBMA/DA chain with higher catechol content provides more anchoring sites to enhance zwitterionic moieties coverage on substrates. Interestingly, atomic force microscopy (AFM) images revealed a smooth and uniform deposition of pSBMA/DA using the pH-transition method. Strong ionic hydration of pSBMA/DA coating on nitinol surface repels non-specific adsorption of bio-foulants, permitting excellent antifouling properties. Zwitterion-modified nitinol achieved a reduction rate of 99.9% against Escherichia coli and Staphylococcus aureus attachment. In addition, pSBMA/DA exhibits a robust antifouling performance to NIH 3T3 mouse fibroblasts in culture media after incubation for 24 h. Overall, the pSBMA/DA coating via pH transition approach opens up a promising strategy to facilitate uniform surface functionalization for antifouling and coating technology.

Dopamine-Initiated Photopolymerization for a Versatile Catechol-Functionalized Hydrogel.

Biomimetic catechol-functionalized hydrogels have attracted substantial attention due to their potential in a variety of biomedical applications, such as tissue repair and regeneration, drug delivery, and antimicrobial and antifouling applications. In this study, a one-pot strategy for fabrication of functional catecholic hydrogels using dopamine as a photoinitiator was developed. Under UV irradiation in an acidic solution, dopamine generates free radicals, likely semiquinone radicals, to trigger the addition polymerization, following pseudo-first-order kinetics. The dopamine-initiated photopolymerization provides a straightforward and facile approach and, in addition, prevents the undesirable oxidation to catecholic groups. Superhydrophilic sulfobetaine methacrylate (SBMA) was applied for developing biocompatible hydrogels. 1H nuclear magnetic resonance, UV-vis spectroscopy, gel permeation chromatography, and rheological studies were conducted to explore the polymerization mechanism and optimal experimental conditions in terms of pH, UV doses, and the concentration of dopamine. The unique properties of the resultant catechol-functionalized pSBMA hydrogels were demonstrated by enhanced mechanical properties through metal-catechol complexation, self-healing and injectable capability, high adhesiveness, and fouling resistance. Consequently, the synthetic strategy to design catecholic hydrogels can leverage the use of dopamine in a variety of applications.

Tough Polyelectrolyte Hydrogels with Antimicrobial Property via Incorporation of Natural Multivalent Phytic Acid.

Tough and antimicrobial dual-crosslinked poly((trimethylamino)ethyl methacrylate chloride)-phytic acid hydrogel (pTMAEMA-PA) has been synthesized by adding a chemical crosslinker and docking a physical crosslinker of multivalent phytic acid into a cationic polyelectrolyte network. By increasing the loading concentration of PA, the tough hydrogel exhibits compressive stress of >1 MPa, along with high elasticity and fatigue-resistant properties. The enhanced mechanical properties of pTMAEMA-PA stem from the multivalent ion effect of PA via the formation of ion bridges within polyelectrolytes. In addition, a comparative study for a series of pTMAEMA-counterion complexes was conducted to elaborate the relationship between swelling ratio and mechanical strength. The study also revealed secondary factors, such as ion valency, ion specificity and hydrogen bond formation, holding crucial roles in tuning mechanical properties of the polyelectrolyte hydrogel. Furthermore, in bacteria attachment and disk diffusion tests, pTMAEMA-PA exhibits superior fouling resistance and antibacterial capability. The results reflect the fact that PA enables chelating strongly with divalent metal ions, hence, disrupting the outer membrane of bacteria, as well as dysfunction of organelles, DNA and protein. Overall, the work demonstrated a novel strategy for preparation of tough polyelectrolyte with antibacterial capability via docking PA to open up the potential use of PA in medical application.

Pegylated Metal-Phenolic Networks for Antimicrobial and Antifouling Properties.

Metal-phenolic networks (MPNs) have recently attracted great interest in material chemistry and biomaterials because of their biocompatible, versatile, and multifunctional properties. In this paper, we describe a facile method for preparation of a designable antifouling, antimicrobial, and substrate-independent coating assembled from the coordination of metal ions and catecholic groups. Hydrophilic and catecholic polymers were synthesized by copolymerization of dopamine methacrylamide (DMA) and poly(ethylene glycol)methyl methacrylate (PEGMA) to afford p(PEGMA- co-DMA). To investigate the assembly and formation of MPN films, two different metal ions, that is, ferrous (FeII) and ferric (FeIII) ions, to react with p(PEGMA- co-DMA) were compared. The binding constants between iron ions and p(PEGMA- co-DMA) have been investigated by ultraviolet-visible spectroscopy (UV-vis). Measurements with atomic force microscopy, contact angle goniometer, and X-ray photoelectron spectroscopy (XPS) were carried out to quantitatively analyze the surface morphology, wettability, and interfacial elemental compositions of coatings, respectively. Moreover, ellipsometric measurements were performed to obtain the film thickness and grafting density. In addition, the pH-responsive property of the MPN films was investigated at different pH values, showing fast disassembly of the networks at low pH. The antifouling properties of the obtained coatings were analyzed by exposing them to bacteria of Escherichia coli and Staphylococcus epidermidis and NIH-3T3 fibroblasts under observation of fluorescence microscopy and cell imaging analysis. The findings suggest that the MPN from complexation of p(PEGMA- co-DMA) and metal ions provides excellent antifouling, pH-responsive, and biocompatible properties on a wide range of substrates. Furthermore, the released iron ions can effectively suppress the growth of bacteria. Accordingly, the new coating architecture offers a universal feature to control surface properties and functionalization for various applications.