Light-Activated, Bioadhesive, Poly(2-hydroxyethyl methacrylate) Brush Coatings

Abstract

Rapid adhesion between tissue and synthetic materials is relevant to accelerate wound healing and to facilitate the integration of implantable medical devices. Most frequently, tissue adhesives are applied as a gel or a liquid formulation. This manuscript presents an alternative approach to mediate adhesion between synthetic surfaces and tissue. The strategy presented here is based on the modification of the surface of interest with a thin polymer film that can be transformed on-demand, using UV-light as a trigger, from a nonadhesive into a reactive and tissue adhesive state. As a first proof-of-concept, the feasibility of two photoreactive, thin polymer film platforms has been explored. Both of these films, colloquially referred to as polymer brushes, have been prepared using surface-initiated atom transfer radical polymerization (SI-ATRP) of 2hydroxyethyl methacrylate (HEMA). In the first part of this study, it is shown that direct UV-light irradiation of PHEMA brushes generates tissue-reactive aldehyde groups and facilitates adhesion to meniscus tissue. While this strategy is very straightforward from an experimental point of view, a main drawback is that the generation of the tissue reactive aldehyde groups uses the 250 nm wavelength region of the UV spectrum, which simultaneously leads to extensive photodegradation of the polymer brush. The second part of this report outlines the synthesis of PHEMA brushes that are modified with 4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzoic acid (TFMDA) moieties. UV-irradiation of the TFMDA containing brushes transforms the diazirine moieties into reactive carbenes that can insert into C−H, N−H, and O−H bonds and mediate the formation of covalent bonds between the brush surface and meniscus tissue. The advantage of the TFMDA-modified polymer brushes is that these can be activated with 365 nm wavelength UV light, which does not cause photodegradation of the polymer films. While the work presented in this manuscript has used silicon wafers and fused silica substrates as a first proof-of-concept, the versatility of SI-ATRP should enable the application of this strategy to a broad range of biomedically relevant surfaces.

Aldehyde-Functional Diblock Copolymer Nano-objects via RAFT Aqueous Dispersion Polymerization

“…This is perhaps surprising because aldehyde chemistry offers many possibilities for derivatization. In particular, conjugation to amine-functional (macro)­molecules via Schiff base chemistry can be conducted in aqueous solution under mild conditions, which is expected to offer potential biomedical applications. − Recently, we reported the synthesis of a new methacrylic monomer (GEO5MA; see Scheme S1) that resembles both glycerol monomethacrylate and oligo­(ethylene glycol) methacrylate . Selective oxidation of the pendent cis -diol groups in GEO5MA (or its corresponding PGEO5MA homopolymer) using aqueous sodium periodate introduces a geminal diol group, which is simply the hydrated form of an aldehyde group.…”

One-Step Liquid Phase Polymerization of HEMA by Atmospheric-Pressure Plasma Discharges for Ti Dental Implants

“…Even though PHEMA coatings have been reported to be antifouling and reduce the protein adsorption and cell adhesion [65], there are also reports regarding the ability of such coatings to allow cell adhesion [60]. Moreover, some modifications of the coatings, such as UV cross-linking, can impart chemical functionalities which enhance cell adhesion [71]. In the case of fibroblasts, a good adhesion brings forward the possibility of optimum biosealing around the implant, which further avoids bacterial infiltration and infection [72,73].…”

A guide to functionalisation and bioconjugation strategies to surface-initiated polymer brushes

“…43,58 For example, the HHC-36 antimicrobial peptide was coupled to the carboxyl side chains of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate)-poly(methacrylic acid) (PDMAPS-b-PMAA) brushes, generated via SI-ATRP from the surface of polyurethane catheters, to prevent biofilm and thrombus formation. 14,79 For similar applications, poly(g-tert-butyl-L-glutamic acid)-b-poly-(sarcosine) brushes were grafted from titanium dioxide surfaces. Conjugation with dopamine via amide bond formation, with 56-65% conversion, enabled the formation of silver particles at corresponding surfaces, upon reduction of silver ions by catechol functions.…”

“…9 This includes mediating cell or tissue bonding, or to design implant coatings, cell based assays and gene delivery systems. [13][14][15][16][17][18][19][20] Although some inherently functional polymer brushes have been reported, for example to promote electron transfer or to confer antibacterial properties, 21,22 in most cases the functional properties and performance of brushes are achieved through the coupling of chemical moieties to usual polymer brushes. Unlike polymer coatings generated via a ''grating to'' approach, which allows functionalisation of precisely designed and characterised macromolecular structures [23][24][25] prior to coupling to a surface (but at low density), polymer brushes generated via a grafting from approach, often using surface-initiated radical polymerisation techniques, 3,4,26 are more challenging to functionalise, owing to the steric hindrance associated with dense chain packings.…”