Biofunctional and biomimetic polymer brushes prepared via surface-initiated atom transfer radical polymerization

Surface-initiated controlled radical polymerization is a powerful strategy to tailor the chemical and physical surface properties of materials. This article highlights recent work from the author's laboratory in which surface-initiated atom transfer radical polymerization is used to generate biofunctional and biomimetic surface coatings. Three examples will be discussed. The first two examples are based on the surface-initiated atom transfer radical polymerization of 2-hydroxyethyl methacrylate and (polyethylene glycol) methacrylate, which generates a polymer brush that suppresses non-specific adhesion of proteins and cells. These non-fouling brushes have been used to generate protein microarrays and to produce coatings that can promote endothelialization of implantable biomaterials. The third example describes the use of polyelectrolyte brushes as matrices to direct the mineralization of calcium carbonate. © Schweizerische Chemische Gesellschaft.

Mechanochemically Responsive Surfaces and Soft Tissue Adhesive Interfaces Generated via Controlled Radical Polymerization

Nariye Cavusoglu Ataman

Thin coatings applied to surfaces dramatically improve the properties of materials. Thus, they have found application in a broad variety of areas including biomedicine, nanotechnology, bioelectronics and optics, amongst others. Polymer brushes prepared via surface-initiated controlled radical polymerization (SI-CRP) techniques represent a versatile class of thin polymer coatings that provide manifold opportunities to engineer surface and interface properties. Densely grafted polymer brushes prepared via SI-CRP possess several attractive material properties such as low friction coefficients and the ability to prevent biofouling, which are related to the stretched conformation of the surface tethered polymer chains. Those distinctive characteristics of polymer brushes make them highly appealing to engineer the properties of functional interfaces. A first aim of this Thesis is to investigate the mechanochemistry of hydrophilic polymer brushes prepared via surface-initiated atom transfer radical polymerization (SI-ATRP) from silica substrates. The second aim of the Thesis is to explore poly(2-hydroxyethyl methacrylate) (PHEMA) based polymer brushes as soft-tissue adhesives in wet tissue environment. This Thesis is divided into four chapters, which are briefly summarized below. Chapter 1 provides a summary of recent literature that has reported detachment or degrafting of densely grafted hydrophilic polymer brushes from substrates upon exposure to aqueous media. The collective results from these reports suggest that swelling-induced stretching of hydrophilic polymer brushes lead to mechanochemical activation of the bonds near the brush-substrate interface and subsequently facilitates hydrolytic chain cleavage. Chapter 2 aims to shed light on the influence of two fundamental structural polymer brush parameters on the degrafting of surface-tethered, densely grafted polymer chains, viz. (i) the chemical composition of the ATRP initiator that is used to grow the polymer brushes and (ii) the effect of surface curvature. To this end, a series of poly(poly(ethylene glycol) methacrylate) (PPEGMA) and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMEMA) brushes were grafted from both flat silica substrates as well as silica nanoparticles. Subsequently, the degrafting of the surface-tethered polymer chains was investigated in cell culture medium and phosphate buffered saline (PBS) using various techniques. The aim of the final two Chapters of this Thesis is less on exploring the chain conformation of polymer chains grafted by SI-CRP, but more to use the ability of SI-CRP to prepare thin polymer films that present a high surface concentration of functional groups to mediate soft tissue adhesion. Chapter 3 describes the preparation of photo-active poly(2-hydroxyethyl methacrylate) (PHEMA) brushes as soft tissue bioadhesives. Tissue adhesion in this Chapter is induced as UV-irradiation of PHEMA brushes converts the initially bio-inert side chain hydroxyl groups of these brushes into (putatively) aldehyde groups, which can react with amine groups present in the tissue. The prepared PHEMA brush coated substrates are biocompatible, which avoids fibrous capsule formation and presents functionalities that can be transformed, on-demand, from a non-reactive, non-adhesive state to a reactive, adhesive state in wet tissue environment. While the photoactivation of the PHEMA side chain functional groups is very efficient, it is not very well defined from a chemistry point of view. Chapter 4 therefore, explores an alternative photoactivation chemistry, which is based on the use of the diazirine motif. These diazirine motifs were incorporated in poly(2-hydroxyethyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) (P(HEMA-co-PEGMEMA)) copolymer brushes via post-polymerization modification. These diazirine modified brushes are attractive as they may not only be activated by UV-light but also by electrochemical means.

EPFL2016

Effects of Grafting Density and Film Thickness on the Adhesion of Staphylococcus epidermidis to Poly(2-hydroxy ethyl methacrylate) and Poly(poly(ethylene glycol)methacrylate) Brushes

Sorin Alexandru Ibanescu, Harm-Anton Klok

Thin polymer films that prevent the adhesion of bacteria are of interest as coatings for the development of infection-resistant biomaterials. This study investigates the influence of grafting density and film thickness on the adhesion of Staphylococcus epidermidis to poly(poly(ethylene glycol) methacrylate) (PPEGMA) and poly(2-hydroxyethyl methacrylate) (PHEMA) brushes prepared via surface-initiated atom transfer radical polymerization (SI-ATRP). These brushes are compared with poly(ethylene glycol) (PEG) brushes, which are obtained by grafting PEG onto an epoxide-modified substrate. Except for very low grafting densities (rho = 1%), crystal violet staining experiments show that the PHEMA and PPEGMA brushes are equally effective as the PEG-modified surfaces in preventing S. epidermis adhesion and do not reveal any significant variations as a function of film thickness or grafting density. These results indicate that brushes generated by SI-ATRP are an attractive alternative to grafted-onto PEG films for the preparation of surface coatings that resist bacterial adhesion.

Wiley-Blackwell2016

Functional polymer brushes via surface-initiated controlled radical polymerizations

Stefano Tugulu

The term polymer brush refers to a well defined arrangement of polymer chains, which are tethered with one end to an interface and usually the surface of a solid substrate. Due to steric repulsion the polymer chains furthermore adopt a defined, stretched chain conformation, which significantly differs from the random walk conformation of free polymer chains in solution or in conventionally solution casted polymer coatings. From a structural point of view polymer brushes can therefore be regarded as the most defined type of polymer coating that can currently be realized. Especially the combination of surface-initiated polymerizations (SIP) with modern, controlled polymerization methods thereby allows tailoring the structure of the polymer brushes almost on the molecular level. Specifically precise control over the thickness, composition, chain architecture, grafting density and via the use of lithographic techniques also over the topography of the brushes can be achieved. This high degree of control over the structural and implicated (physico-)chemical properties of the brush allows at the same time tailoring and fine tuning the interfacial properties of the brush. This thesis describes the systematic exploitation of well-defined polymer brushes as functional coatings with fine-tuned physicochemical properties to direct and control the interaction with and the response of specific biological, bioanalytical and even reactive chemical environments. In detail the use of surface-initiated atom transfer radical polymerization (SI-ATRP) for the fabrication of functional polymer brushes will be presented. These brushes were used as highly defined coatings in various applications ranging from biomedical and bioanalytical applications to biomimetic materials fabrication (Figure 1). Figure 1 Numerous synthetic approaches for the preparation of polymer brushes have been described in the literature. Chapter 2 will therefore present a summary of the most important types of surface-initiated polymerizations, focusing especially on controlled SIP methods and SI-ATRP. Chapter 3 describes a chemoselective and specific immobilization strategy to decorate intrinsically bioinert polymer brushes with proteins of interest in a defined orientation and density. Specifically the resulting substrates represent attractive candidates for the realization of protein microarrays. In view of this application protein-small molecule and protein-protein interactions as well as posttranslational modifications were analyzed within a feasibility study. Due to their well-defined structure polymer brushes represent also attractive candidates for the realization of molecularly defined cell adhesion substrates for tissue engineering or as highly defined biophysical model system to analyze cell adhesion and mechanics. Chapter 4 describes the decoration of intrinsically bioinert polymer brushes with small peptide ligands with defined density to induce integrin specific cell adhesion on the brushes. Peptide functionalized polymer brushes could be readily endothelialized and adhering cell layers have shown to preserve their homeostatic ability to respond to an applied mechanical stimulus in a physiological manner. In Chapter 5 the limitations of high density polymer brushes in biomedical applications were assessed by analyzing their stability under in vitro cell culture conditions. Intrinsically bioinert high density polymer brushes were found to degraft from glass or silicon substrates upon swelling in good solvents, which lead to deterioration of the bioinert properties of the substrate. The degrafting of the brushes might be connected to swelling induced mechanical activation of chemical bonds, which link the brushes to the substrate. Chapter 6 describes the transfer of the developed SIP approach onto flexible PDMS substrates by exploiting the formation of interpenetrating networks of ATRP-initiator siloxane and PDMS. The modification of the PDMS substrates with hydrophilic brushes effectively reduces the unspecific protein adsorption on the substrates. This approach might therefore represent an attractive and facile route for the surface modification of miniaturized PDMS devices for biomedical or bioanalytical applications. In Chapter 7 the systematic development of a reliable and robust protocol for the aqueous SI-ATRP of sodium methacrylate is presented, which gives access to poly(methacrylic acid) (PMAA) brushes with defined molecular weight and grafting density. The resulting brushes were assessed for their ability to direct the mineralization of calcium carbonate. Chapter 8 describes the use of photolithographically patterned poly(methacrylic acid) brushes as biomimetic, acidic macromolecular matrix to fabricate microstructured calcite thin films that are an exact 3D replica of the PMAA brush. The presented strategy relies on three key elements: (i) the use of photolithographic techniques to prepare microstructured PMAA brushes; (ii) the ability of PMAA brushes to stabilize amorphous calcium carbonate (ACC) and (iii) the possibility to convert the metastable ACC phase into a polycrystalline calcite film via a thermal treatment.