Controlling Cell Adhesion to Titanium: Functionalization of Poly[oligo(ethylene glycol)methacrylate] Brushes with Cell‐Adhesive Peptides

Abstract

Titanium and its alloys represent a major class of materials employed in orthopedic and dental clinical applications. Although titanium-based implants can function effectively for a decade, the long-term clinical success of these devices is limited by implant loosening and wear, especially in younger patients. [1,2] Considerable efforts have focused on implant surface technologies, such as designing rough, porous coatings for bone ingrowth, and bone-bonding ceramic coatings to promote integration into the surrounding bone and thereby enhance mechanical interlock. [1,3,4] However, slow rates of osseointegration, particularly in clinically challenging cases, currently restrict these approaches. Biomimetic coatings, focusing on the presentation of biologically active molecules within a protein adsorption-resistant background, have recently emerged as a promising strategy to enhance osseointegration.[5]Self-assembled monolayers (SAMs) have been explored as a method to control biologically related surface properties such as cell adhesion. [6][7][8][9][10] For example, we have previously demonstrated control over protein adsorption and cell adhesion and function by modification of oligo(ethylene glycol)-substituted alkanethiol monolayers on gold with specific peptide sequences from adhesion proteins. [11][12][13] However, SAMs on gold and silver substrates suffer from long-term instability and loss of bioresistance, and there are severe limitations to the application of robust noble-metal coatings on biomedical materials. [6][7][8][9] To overcome these shortcomings, several groups have concentrated on the engineering of polymeric films on titaniumand silicon-based surfaces to promote robust bioresistance. [14][15][16][17] For instance, adsorption of end-functionalized poly(ethylene glycol) (PEG) onto titanium metal (i.e., a "grafting-to" approach to prepare polymer brushes) affords resistance to protein adsorption.[10] More recently, a "graftingfrom" approach was developed based on surface-initiated atom-transfer radical polymerization (SI-ATRP) of oligo(ethylene glycol)methacrylate (OEGMA) on gold modified with a thiol monolayer of an a-bromo ester initiator. An extensive study of the properties of these brushes was carried out as a function of polymerization time and the surface density of initiator. This afforded the ability to control the thickness of the poly(OEGMA) film and demonstrated the resistance of these surfaces to cell adhesion. [9,16,18] To build on these findings and to explore the development of stable surface modifications of titanium, we set out to establish routes to prepare protein-adsorption-resistant polymer brushes that can be modified with peptide sequences that direct cell adhesion. We describe an approach to modify the surface of titanium with dense polymer brushes of poly(OEGMA) that resist protein adsorption and cell attachment. Furthermore, conversion of the hydroxyl end groups of the oligo(ethylene glycol) (OEG) side chains to 4-nitrophenyl carbonate groups allows for tethering of bioacti...

The effect of integrin-specific bioactive coatings on tissue healing and implant osseointegration

“…The progress of the synthesis and ligand tethering was validated by comparison of spectra from X-ray photoelectron spectroscopy (XPS) and glancing angle Fourier transform infrared (FTIR) spectroscopy with spectra from previously published characterization of these poly(OEGMA) brushes [18]. Brush thickness was easily modulated by polymerization time as previously shown [18]. All poly (OEGMA) brushes used in this study were grown to a thickness of 135 Å.…”

“…We employed a "grafting from" approach based on surface-initiated atom-transfer radical polymerization (SI-ATRP) of poly(OEGMA) brushes on titanium [18] (Fig. 1A).…”

“…Polymeric brushes, which are arrays of polymer chains attached at one end to a surface, on titanium substrates were synthesized by surface-initiated atom-transfer radical polymerization of poly(oligo(ethylene glycol) methacrylate) (poly(OEGMA)) [18]. Titanium-coated glass slides or custom-made commercially pure titanium implants were incubated in a 1:1 solution of chlorodimethyl(11-(2-bromo-2-methylpropionyloxy)undecyl)silane and dodecyldimethylchlorosilane in anhydrous hexane.…”

Polymer brushes and self-assembled monolayers: Versatile platforms to control cell adhesion to biomaterials (Review)

“…2͑A͒. Other combinations of adsorbates and substrates include chlorosilanes on silicon oxide, 77,78 aluminum, 79 and titanium; 80 phosphonic acids on aluminum 79 or titanium; 81,82 and catechol derivatives on titanium. 83 Although alkanethiol SAMs on gold are most commonly studied, they suffer from instability of the thiolgold bond leading to facile exchange of the adsorbates.…”

GFOGER-Modified MMP-Sensitive Polyethylene Glycol Hydrogels Induce Chondrogenic Differentiation of Human Mesenchymal Stem Cells

“…36 Moreover, type II collagen-induced GAG deposition in chondrocytes was inhibited by GFOGER integrin blocking peptides. 37 The GFOGER sequence has been used to modify surfaces [38][39][40] and hydrogels 37,41 to control adhesion and gene expression of chondrocytes and differentiation of stem cells. When bone marrow stromal cells were encapsulated in an agarose gel with covalently coupled GFOGER peptides, type II collagen, and aggrecan mRNA stimulation and GAG deposition by transforming growth factor beta (TGF-b) and dexamethasone was inhibited.…”