Biological response on a titanium implant-grade surface functionalized with modular peptides

Abstract

Titanium (Ti) and its alloys are among the most successful implantable materials for dental and orthopedic applications. The combination of excellent mechanical and corrosion resistance properties makes them highly desirable as endosseous implants that can withstand a demanding biomechanical environment. Yet, the success of the implant depends on its osteointegration, which is modulated by the biological reactions occurring at the interface of the implant. A recent development for improving biological responses on the Ti-implant surface has been the realization that bifunctional peptides can impart material binding specificity not only because of their molecular recognition of the inorganic material surface, but also through their self-assembly and ease of biological conjugation properties. To assess peptide-based functionalization on bioactivity, the present authors generated a set of peptides for implant-grade Ti, using cell surface display methods. Out of 60 unique peptides selected by this method, two of the strongest titanium binding peptides, TiBP1 and TiBP2, were further characterized for molecular structure and adsorption properties. These two peptides demonstrated unique, but similar molecular conformations different from that of a weak binder peptide, TiBP60. Adsorption measurements on a Ti surface revealed that their disassociation constants were 15-fold less than TiBP60. Their flexible and modular use in biological surface functionalization were demonstrated by conjugating them with an integrin recognizing peptide motif, RGDS. The functionalization of the Ti surface by the selected peptides significantly enhanced the bioactivity of osteoblast and fibroblast cells on implant-grade materials.

Aqueous Peptide–TiO2 Interfaces: Isoenergetic Binding via Either Entropically or Enthalpically Driven Mechanisms

“…This approach resulted in predictions of over-structuring, chiefly attributed to the formation of helices in the implicit solvent simulations, which persisted once these structures were transferred into a liquid water environment (see 'Implicit Solvent Simulations' in the Supporting Information for methodology and results). These findings highlight that data generated using such approaches, for instance those published previously 36 , should be interpreted with caution. Implicit-solvent models, even when followed up with explicit solvation simulations, should not be used to characterize the conformational ensemble of materials-binding peptides.…”

“…26 The tripeptide motif RGD and its interaction with titania surfaces has been of particular interest, [27][28][29][30][31][32][33] while others have sought to isolate and identify TiO2-binding peptides using biocombinatorial techniques to gain a deeper understanding of which peptide characteristics can confer strong titania-binding affinity. 32,[34][35][36][37] A crucial next step in advancing our understanding is the careful characterization of the adsorption of materials-binding peptides at aqueous titania interfaces. [36][37][39][40][41][42][43] Of particular note is the work of Yazici et al 36 who used quartz crystal microbalance (QCM) measurements to determine the binding free energy of three sequences; two "strong-binders", RPRGNRGRERGL and SRPNGYGGSESS, with Gads= -34.5 and -38.5 kJ mol -1 respectively and one "weak-binder", VGRVTSPRPQGR, with Gads= -27.6 kJ mol -1 , identified from cell-surface display screening experiments.…”

“…32,[34][35][36][37] A crucial next step in advancing our understanding is the careful characterization of the adsorption of materials-binding peptides at aqueous titania interfaces. [36][37][39][40][41][42][43] Of particular note is the work of Yazici et al 36 who used quartz crystal microbalance (QCM) measurements to determine the binding free energy of three sequences; two "strong-binders", RPRGNRGRERGL and SRPNGYGGSESS, with Gads= -34.5 and -38.5 kJ mol -1 respectively and one "weak-binder", VGRVTSPRPQGR, with Gads= -27.6 kJ mol -1 , identified from cell-surface display screening experiments. We note that these measurements were done in phosphate buffered saline solution, and their binding target was a Ti film generated using chemical vapour deposition, chemically similar to implant-grade Ti, while the target for their cell-surface display experiments was implant grade titanium with a naturally oxidized layer.…”

Combining 3D human in vitro methods for a 3Rs evaluation of novel titanium surfaces in orthopaedic applications

“…The use of human cells is another advantage—here an MG63 osteoblast‐like cell line (Chang et al, 2014; Gittens et al, 2011; Madhankumar et al, 2014; Tan et al, 2011; Yazici et al, 2013; Yeung et al, 2013) and primary human osteoblast cells (Balani et al, 2007; Gough et al, 2004; Jones et al, 2007; Rice et al, 2003) were used. Although the MG63 cell line is immortalized (Schmidt et al, 2001), such cells are suitable for establishing initial experimental conditions.…”

Harnessing the power of microbial nanowires

“…The self‐assembly properties of some peptides have also attracted substantial interest in nanotechnology. The osteointegration of orthopaedic and dental titanium implants can, for example, be improved with coatings of bifunctional peptides selected for their ability to simultaneously bind the titanium alloy and the targeted tissue (Yazici et al ., 2013). Peptide self‐assemblies have also inspired designs of molecular surface coatings used in cell adhesion assays (Chen et al ., 1997) and biosensors (Templin et al ., 2002; Bertone and Snyder, 2005; Ma et al ., 2012; Gupta et al ., 2016).…”