In this work, we report a systematic study of zwitterionic poly(carboxybetaine methacrylate) (pCBMA) grafted from glass surfaces via atom transfer radical polymerization (ATRP) for their resistance to long-term bacterial biofilm formation. Results show that pCBMA-grafted surfaces are highly resistant to nonspecific protein adsorption (fibrinogen and undiluted blood plasma) at 25, 30 and 37 °C. Long-term (over 24 h) colonization of two bacterial strains (Pseudomonas aeruginosa PAO1 and Pseudomonas putida strain 239) on pCBMA surface was studied using a parallel flow cell at 25, 30 and 37 °C. Uncoated glass cover slips were chosen as the positive reference. Results show that pCBMA coatings reduced long-term biofilm formation of P. aeruginosa up to 240 h by 95% at 25 °C and for 64 h by 93% at 37 °C, and suppressed P. putida biofilm accumulation up to 192 h by 95% at 30 °C, with respect to the glass reference. The ability of pCBMA coatings to resist non-specific protein adsorption and significantly retard bacterial biofilm formation makes it a very promising material for biomedical and industrial applications.

Human blood serum and plasma pose significant challenges to blood-contacting devices and implanted materials because of their high nonspecific adsorption onto surfaces. In this work, we investigated nonspecific protein adsorption from single protein solutions and complex media such as undiluted human blood serum and plasma onto poly(carboxybetaine acrylamide) (polyCBAA)-grafted surfaces at different temperatures. The polyCBAA grafting was done via atom-transfer radical polymerization (ATRP) with varying film thicknesses. The objective is to create a surface that experiences "zero" protein adsorption from complex undiluted human blood serum and plasma. Results show that protein adsorption from undiluted human blood serum, plasma, and aged serum on the polyCBAA-grafted surface is undetectable at both 25 and 37 degrees C by a surface plasmon resonance (SPR) sensor. This was achieved with a film thickness of approximately 21 nm. Furthermore, it is demonstrated that the polyCBAA surfaces after antibody immobilization maintain undetectable protein adsorption from undiluted human blood serum. This is the first time that an effective nonfouling material suitable for applications in complex blood media has been demonstrated.

Zwitterionic carboxybetaine (CB) has unique dual functionality for ligand immobilization on a nonfouling background. The properties of CB groups depend on their spacer groups between the positive quaternary amine groups and the negative carboxyl groups and environmental factors (e.g., ionic strengths and pH values). In this work, five polycarboxybetaines were prepared, including one polycarboxybetaine methacrylate (polyCBMA) and four polycarboxybetaine acrylamides (polyCBAAs) with different spacer groups. The polymers were grafted from a gold surface covered with initiators using surface-initiated atom transfer radical polymerization. Fibrinogen adsorption was measured as a function of ionic strengths and pH values using surface plasmon resonance sensors. The responsive protein adsorption on four polyCBAAs was mapped out. Results show that most of these surfaces exhibit high protein resistance in a wide range of ionic strengths and are more effective than zwitterionic self-assembled monolayers. Although protein adsorption tends to increase at low ionic strength and low pH value, it is still very low for polycarboxybetaines with a methylene, an ethylene, or a propylene spacer group but is more evident for polyCBAA with a longer spacer group (i.e., a pentene group). The response to ionic strengths and pH values can be attributed to the antipolyelectrolyte and protonation/deprotonation properties of polycarboxybetaines, respectively. Both of these properties are related to the spacer groups of CBs.

Microbial adhesion onto implanted biomaterials and the subsequent formation of biofilms is one of the major causes of biomedical device failure. The use of antimicrobial and nonfouling coatings are two strategies for the prevention of the attachment and spreading of microorganisms on the surfaces of implantable materials. Antimicrobial surfaces containing covalently linked quaternary ammonium compounds (QACs) have proved to be able to efficiently kill a variety of microorganisms. [1][2][3][4][5][6][7] A major problem with QAC surfaces is the attachment of dead microorganisms remaining on antimicrobial coatings, which can trigger an immune response and inflammation, and block its antimicrobial functional groups. In addition, such antimicrobial coatings can not fulfill the requirements of nonfouling [8] and biocompatibility as implantable biomaterials. Poly(ethylene glycol) (PEG) derivatives [9][10][11][12][13][14] or zwitterionic polymers [15][16][17][18] have been extensively used as nonfouling materials to reduce bacterial attachment and biofilm formation. However, the susceptibility of PEG to oxidation damage has limited its long-term application in complex media. [11,19] We recently showed that zwitterionic materials such as poly(sulfobetaine methacrylate) (pSBMA) were able to dramatically reduce bacterial attachment and biofilm formation [18] and were highly resistant to nonspecific protein adsorption, even from undiluted blood plasma and serum. [20][21][22][23][24] Although zwitterionic coatings can reduce the initial attachment and delay colonization of microbes on surfaces, there is a possibility of introducing pathogenic microbes into the patient during implantation operations and catheter insertions, which results in the failure of implanted devices; the use of antimicrobial agents will then be necessary to eliminate these microbes. Surface-responsive materials have been developed for a broad spectrum of applications, [25] but it is still a great challenge to develop biocompatible materials that have both antimicrobial and nonfouling capabilities. To the best of our knowledge, no such materials have been reported to date.Herein we report a new switchable polymer surface coating, which combines the advantages of both nonfouling and cationic antimicrobial materials and overcomes their disadvantages (Figure 1). In this system, poly(N,N-dimethyl-N-(ethoxycarbonylmethyl)-N-[2'-(methacryloyloxy)ethyl]-ammonium bromide) (pCBMA-1 C2, cationic precursor) on a surface can kill greater than 99.9 % of Escherichia coli K12 in one hour, and 98 % of the dead bacterial cells can be released when the cationic derivatives are hydrolyzed to nonfouling zwitterionic polymers. pCBMA-1 C2 and control coatings were grafted by surface-initiated atom transfer radical polymerization (ATRP) onto a gold surface covered with initiators. The thicknesses of the obtained polymer coatings, as measured by atomic force microscopy (AFM), [26] were 26-32 nm (Table 1).The bactericidal activity of pCBMA-1 C2 surfaces was determined using E. co...

In this work, we investigate protein adsorption from single protein solutions and complex media such as 100% blood serum and plasma onto poly(sulfobetaine methacrylate) (polySBMA)-grafted surfaces via atom transfer radical polymerization (ATRP) at varying film thicknesses. It is interesting to observe that protein adsorption exhibits a minimum at a medium film thickness. Results show that the surface with 62 nm polySBMA brushes presents the best nonfouling character in 100% blood serum and plasma although all of these surfaces are highly resistant to nonspecific protein adsorption from single fibrinogen and lysozyme solutions. Surface resistance to 100% blood serum or plasma is necessary for many applications from blood-contacting devices to drug delivery. This work provides a new in vitro evaluation standard for the application of biomaterials in vivo.

No abstract

Attack or defend! A smart polymer surface has two reversibly switchable equilibrium states, a cationic N,N-dimethyl-2-morpholinone (CB-Ring) and a zwitterionic carboxy betaine (CB-OH). CB-Ring will kill bacteria upon contact under dry conditions, whereas CB-OH will release the previously attached and dead bacteria and further resist adhesion of bacteria under wet conditions.

New energetic salts (4 − 9, 11, 13, 16, 21, 22, 29 − 34, 36, 37, 42, 43, 46, 47) were synthesized via the quaternization of azido or nitro derivatives of imidazole, 1,2,4-triazole, and substituted derivatives of tetrazole with nitric or perchloric acid or with iodomethane followed by metathesis reaction with silver nitrate or silver perchlorate. The structures of 1,4-dimethyl-3-azido-1,2,4-triazolium nitrate (5), 3-azido-1,2,4-triazolium nitrate (6), 1-methyl-4-amino-1,2,4-triazolium perchlorate (16), and 1,4-dimethyl-2-H-1,2,4-triazolium triiodide (20) were confirmed by single-crystal X-ray analysis. Most of the salts exhibit good thermal stabilities and low melting points. By using constant volume combustion energies that were determined experimentally using an oxygen bomb calorimeter, the standard molar enthalpies of formation were derived based on designed Hess thermochemical cycles.