Thiol-Reactive Polymers for Titanium Interfaces: Fabrication of Antimicrobial Coatings

Abstract

Infection associated with surgical implants is a major cause of their failure. Often in such cases, the implant has to be removed and replaced, which causes undesirable patient discomfort and complications. Bacterial adhesion and growth on implant surface is the primary reason for such infections. Among the approaches to prevent implant associated infections, the conjugation of antimicrobial peptide (AMP) onto the surface of the implant is a very promising approach. In this study, we describe a facile method for the surface modification of titanium (Ti), a widely used material in dental and orthopedic implants, to prevent bacterial adhesion and growth. Thin polymeric films were synthesized on the Ti surface by using a copolymer containing the maleimide group as a thiol-reactive handle to enable the conjugation of AMPs. Robust attachment of the polymeric coating on Ti surfaces was ensured through installation of catechol moieties on the polymer as surface anchoring groups and the variation of the amount of thiol-reactive maleimide group on titanium surfaces. As a proof of concept, to demonstrate a viable application of such thiol reactive surfaces, the antimicrobial peptide E6 (RRWRIVVIRVRRC) was immobilized onto these well-characterized thin polymeric layers through Michael addition. The antimicrobial activity of peptide-modified surfaces was screened against both Gram-positive and Gram-negative bacteria. The hydrophilic polymer coatings decreased the bacterial adhesion, and the immobilized peptide killed >80% of the adhered bacteria. The developed surface modification method has broad applicability in terms of the choice of substrates and peptides in the design of bioactive surfaces.

Multifunctional and Transformable ‘Clickable’ Hydrogel Coatings on Titanium Surfaces: From Protein Immobilization to Cellular Attachment

“…We have earlier reported maleimide-containing polymers [ 45 , 46 ], surfaces [ 47 , 48 , 49 , 50 ] and bulk hydrogels [ 51 ] for biomolecular immobilization [ 52 , 53 ]. In a recent study, copolymers containing dopamine- and maleimide-containing monomers were used to obtain antibacterial coatings on titanium surfaces through attachment of anti-bacterial peptides [ 54 ]. Although the approach was successful to an extent, two critical challenges with this approach were realized.…”

Antimicrobial polymeric paints: An up‐to‐date review

“…One of the ways to prevent biofilm formation is to modify surfaces by bioactive agents. The mode of mechanism for AMC is, it inhibits the microbial growth upon interaction with internal environment or on contact with the surface 5,18–24 . Presence of bacteria in the environment is both beneficial and detrimental hence, rationale of developing antimicrobial surfaces should focus more on microbe‐repelling surfaces 25–27 …”

“…The mode of mechanism for AMC is, it inhibits the microbial growth upon interaction with internal environment or on contact with the surface. 5,[18][19][20][21][22][23][24] Presence of bacteria in the environment is both beneficial and detrimental hence, rationale of developing antimicrobial surfaces should focus more on microbe-repelling surfaces. [25][26][27] Numerous technologies for AMCs are reported in literature:…”

Fabrication of Patterned Hydrogel Interfaces: Exploiting the Maleimide Group as a Dual Purpose Handle for Cross-Linking and Bioconjugation

“…Until recent years, lack of synthetic methodology to obtain polymers containing pendant maleimide functional groups may have contributed to this end. The protection of the polymerizable alkene group of maleimide using a Diels–Alder/retro Diels–Alder sequence has led to access of maleimide-bearing polymers. − In contrast to other photoactive groups, the maleimide moiety is quite attractive because they can not only introduce the desired cross-linking but can also be used as handles for subsequent functionalization. Most of the studies to date have employed the maleimide groups for obtaining cross-linked materials by using the thiol–maleimide and Diels–Alder reactions. − The maleimide units are known to yield dimers containing a fused cyclobutane ring upon UV irradiation. , Despite these scant reports in the literature, the only example that utilized the maleimide group for direct photo-cross-linking is based on a two-photon excitation approach.…”