Polyurea has found applications in protective coatings. Yet, the too fast polymerization and lack of functions limit its application. Herein, we report a high-performance polyurea via the stepwise polymerization of an isocyanate (NCO)-terminated prepolymer consisting of poly(propylene glycol)-block-poly(ethylene glycol)-block-poly(propylene glycol) (PPG-b-PEG-b-PPG) with a nanocluster synthesized via the hydrolysis of N-phenylaminomethyltriethoxysilane. Such a nanocluster contains low-reactivity secondary amines, so the polymerization of polyurea can be slowed down (over 1 h), which improves its wetting and adhesion to a substrate. The residual silanol groups on the nanocluster further increase the adhesion. Such polyurea exhibits high adhesion on various substrates, including glass, ceramic, steel, copper, titanium, wood, and natural rubber (∼2.35-14.64 MPa). Besides, the nanoclusters can cross-link the prepolymer into a tough network, endowing the polyurea with a high mechanical strength of ∼25 MPa, much higher than the traditional polyaspartic ester polyurea. On the other hand, the PEG segments enable the polyurea to have good fouling resistance against proteins (fibrinogen absorption was reduced by over 90%), bacteria (RBA of S. aureusE. coli and Pseudomonas sp. was less than 10%), as well as diatom (diatom density was less than 100 cells/mm2). The polyurea is expected to find applications in biomedical engineering and marine antifouling.

Polysarcosine (PSar) is an electrically neutral and excellently hydrophilic polypeptoid showing limited interaction with proteins and cells, which possesses better biocompatibility compared with polyethylene glycol. However, the immobilization of PSar is difficult due to the high water solubility. Herein, lysine-sarcosine PiPo, which was the random copolymer of lysine and sarcosine (PLS), was synthesized via a phosgene-free and water-tolerable polymerization of N-phenyloxycarbonyl-amino acids for the first time. PLS was immobilized by tannic acid (TA) on the polysulfone (PSf) membrane for a short time to obtain a neutral surface. The modified membrane showed improved hydrophilicity, decreased protein adsorption, and low cytotoxicity. Moreover, barely any hemolysis, no platelet adhesion, prolonged clotting time, and low complement activation further suggested good hemocompatibility. In order to improve the antifouling ability of the membrane under pressure, the neutral surface was oxidized by sodium periodate, which accelerated the chemical reaction between amino groups in PLS and phenolic hydroxyl groups in TA. Meanwhile, carboxyl groups generated due to the decomposition of TA and a negatively charged surface were obtained. While maintaining the good properties of the unoxidized one, the hydrophilicity of the oxidized membrane was improved and the clotting time was further prolonged. Besides, the filtration recovery of the oxidized membrane was improved remarkably. This approach of rapid immobilization of PSar has great potential for applications in the biomedical area, especially for blood-contacting materials.

It is challenging to balance high biocompability with good mechanical-electrical sensing performance, especially when triggering inflammatory stress response after in vivo implantation. Herein, a bioinspired wrinkle-reinforced adaptive nanoclay-interlocked soft strain-sensor based on a highly stretchable and elastic ionic-conductive hydrogel is reported. This novel nanoclay-composite hydrogel exhibits excellent tensile properties and high sensing capacity with steady and reliable sensing performance due to the structural-mechanical-electrical integrity of the nanoclay crosslinked and nano-reinforced interpenetrating network. The incorporation of amphiphilic ions provides the hydrogel with significant protein resistance, reducing its non-specific adsorption to proteins upon implantation, improving its biosafety as an implanted device, and maintaining the authenticity of the sensing results. Based on the revealed sensing enhanced mechanism based on hierarchical ordered structures as a proof-of-concept application, this hydrogel sensor is demonstrated to be able to accurately localize the region where myocardial infarction occurs and may become a novel strategy for real-time monitoring of pathological changes in heart disease.

Modification of gold substrates with a stable, uniform and ultrathin layer of biocompatible materials is of tremendous interest for the development of bio-devices. We present the fabrication of hybrid systems consisting of triangular prism gold nanoparticles (Au@NTPs) covalently covered with tripod-shaped oligo(p-phenylenes) featuring trifluoromethyl groups. Their synthesis is accomplished using a biphenyl boronic ester as the key compound. Au@NTPs were prepared through a seedless procedure using 3-butenoic acid and benzyldimethyl ammonium chloride, and modified with aminothiol groups. Coverage of this amine-modified gold substrate with a self-assembled monolayer (SAM) of tripod-shaped molecules is carried out in ethanolic solution. The hybrid system avoids up to 70 % of protein corona formation, and allows unspecific attachment for bulky adsorbates, providing an optimal biosensing platform. Chemical composition and morphology are analyzed by transmission electron microscopy (TEM), UV-visible spectroscopy and field emission scanning electron microscopy (FESEM).

Poly (ethylene glycol) (PEG)-based nanomedicines are perplexed by the challenges of oxidation damage, immune responses after repeated injections, and limited excretion from the body. As an alternative to PEG, bioinspired zwitterions bearing an identical number of positive and negative ions, exhibit exceptional hydrophilicity, excellent biomimetic nature and chemical malleability, endowing zwitterionic nano-vectors with biocompatibility, non-fouling feature, extended blood circulation and multifunctionality. In this review, we innovatively classify zwitterionic nano-vectors into linear, hyperbranched, crosslinked, and hybrid nanoparticles according to different chemical architectures in rational design of zwitterionic nano-vectors for enhanced drug delivery with an emphasis on zwitterionic engineering innovations as alternatives of PEG-based nanomedicines. Through combination with other nanostrategies, the intelligent zwitterionic nano-vectors can orchestrate stealth and other biological functionalities together to improve the efficacy in the whole journey of drug delivery.

OBJECTIVE: Although protein adsorption at an interface is very common and important in biology and biotechnology, it is still not fully understood - mainly due to the intricate balance of forces that ultimately control it. In food processing (and medicine), controlling and manipulating protein adsorption, as well as avoiding protein adsorption (biofilm formation or membrane fouling) by the production of protein-resistant surfaces is of substantial interest. A major factor conferring resistance towards protein adsorption to a surface is the presence of tightly bound water molecules, as is the case in oligo ethylene glycol (OEG)-terminated self-assembled monolayers (SAMs). Due to strong attractive protein-protein and protein-surface interactions observed in systems containing trivalent salt ions, we hypothesize that these conditions may lead to a breakdown of protein resistance in OEG SAMs.
METHODS: We studied the adsorption behavior of BLG in the presence of a lanthanum(III) chloride (LaCl3) at concentrations of 0, 0.1, 0.8 and 5.0 mM on normally protein resistant triethylene glycol-termianted (EG3) SAMs on a gold surface. We used quartz-crystal microbalance with dissipation (QCM-D) and neutron reflectivity (NR) to characterize the morphology of the interfacial region of the SAM.
RESULTS: We demonstrate that the protein resistance of the EG3 SAM breaks down beyond a threshold salt concentration c∗ and mirrors the bulk behaviour of this system, showing reduced adsorption beyond a second critical salt concentration c∗∗. These results demonstrate for the first time the controlled switching of the protein-resistant properties of this type of SAM by the addition of trivalent salt.

We attempt to predict the water contact angle (WCA) of self-assembled monolayers (SAMs) and protein adsorption on the SAMs from the chemical structures of molecules constituting the SAMs using machine learning with an artificial neural network (ANN) model. After training the ANN with data of 145 SAMs, the ANN became capable of predicting the WCA and protein adsorption accurately. The analysis of the trained ANN quantitatively revealed the importance of each structural parameter for the WCA and protein adsorption, providing essential and quantitative information for material design. We found that the degree of importance agrees well with our general perception on the physicochemical properties of SAMs. We also present the prediction of the WCA and protein adsorption of hypothetical SAMs and discuss the possibility of our approach for the material screening and design of SAMs with desired functions. On the basis of these results, we also discuss the limitation of this approach and prospects.

In this work, a facile click reaction strategy is employed to form hydrogels in situ with cytocompatibility, biodegradability, self-healing property and resistance to protein. The thiol-functionalized zwitterionic carboxybetaine methacrylate copolymer, which take part as a cross-linker in the \"thiol-ene\" click reaction with the methacrylated hyaluronic acid. The hydrogels are obtained under the physiological condition without the presence of any copper catalyst and UV light. The hydrogel consisting of zwitterionic component shows an obvious reduction in protein adsorption and cell adhesion and avoid non-targeted factor interference in the biological experiments. The hydrogels also demonstrate adjustable degradation behavior. Human mesenchymal stem cells (hMSCs) are easily encapsulated into the hydrogels and remains metabolically active, indicating the excellent biocompatibility of the hydrogels. Additionally, the result of the cytokine secretion assays (IL-6 and TNF-α) has shown that this clickable hydrogel can serve to suppress inflammatory reactions and is beneficial for in vivo applications. Based on the above results, this clickable hydrogel with excellent performance can be an amenable platform for 3D cell encapsulation.

Regeneration of antifouling polymer surfaces after contamination or damage is an important issue, especially in complex marine environments. Here, inspired by the self-renewal of silyl acrylate polymers and the protein resistance of zwitterionic polymers, we prepared a novel hydrolysis-induced zwitterionic monomer, tertiary carboxybetaine triisopropylsilyl ester ethyl acrylate (TCBSA), and copolymerized it with methyl methacrylate (MMA). Such a copolymer rapidly self-generates a zwitterionic surface and provides fouling resistance in marine environments. Furthermore, TCBSA was copolymerized with MMA and 2-methylene-1,3-dioxepane (MDO), where MDO causes degradation of the polymers. Our study demonstrates that the degradation of the polymer is controlled, and the degradation rate increases with the external enzyme concentration in the seawater, leading to a self-renewing dynamic surface. Quartz crystal microbalance with dissipation measurements show that the polymeric coating with self-generating zwitterions has excellent protein resistance in seawater. Bioassays demonstrate that the coating can effectively inhibit the adhesion of marine bacteria (Pseudomonas sp.) and diatoms (Navicula incerta). The coating with a self-generating and self-renewing zwitterionic surface is potential to find applications in marine anti-biofouling.

Poly(N-vinylpyrrolidone) (PVP)-modified surfaces have been shown to possess excellent protein resistance and good biocompatibility. However, PVP-modified surfaces with different molecular architectures have not been prepared, and their protein-resistant properties have not been studied. Herein, gold surfaces modified with linear PVP brush and PVP bottle-brush architectures were prepared by photoinitiated surface grafting polymerization. Ellipsometry, X-ray photoelectron spectroscopy (XPS), water contact angle, Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) were utilized to characterize the prepared surfaces. The protein-resistant properties were investigated by a quartz crystal microbalance with dissipation (QCM-D) with bovine serum albumin (BSA), fibrinogen (Fg) and lysozyme (Lyz). Compared with the ungrafted QCM-D chips, the PVP bottle-brush-grafted chips (9.3 nm thickness) showed superior protein resistance over linear PVP brush-grafted chips (9.9 nm thickness). Furthermore, the PVP bottle-brushes reduced the levels of BSA, Fg and Lyz adsorption by 97%, 85% and 69%, respectively. Moreover, to demonstrate potential applications as functional biosensors and in the biomedical field, PVP bottle-brushes containing glycopolymer-grafted gold surfaces were fabricated. Laser scanning confocal microscopy (LSCM) demonstrated that these glycopolymer surfaces showed excellent protein resistance and specific ConA binding ability. Overall, we speculate that the data presented here can provide useful information for the development of excellent antifouling materials and functional biosensors.