Biocompatible Organic Coatings Based on Bisphosphonic Acid RGD-Derivatives for PEO-Modified Titanium Implants.

Lyudmila V Parfenova,Guzel U Gil'Fanova,Zulfia R Galimshina,Ksenia V Danilko,Ruzil G Farrakhov,Veta R Mukaeva,Grigory S Dyakonov,Evgeny V Parfenov,Elena S Lukina

doi:10.3390/molecules25010229

Lyudmila V Parfenova, Guzel U Gil'Fanova + Show 7 more

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https://doi.org/10.3390/molecules25010229

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Abstract

Currently, significant attention is attracted to the problem of the development of the specific architecture and composition of the surface layer in order to control the biocompatibility of implants made of titanium and its alloys. The titanium surface properties can be tuned both by creating an inorganic sublayer with the desired morphology and by organic top coating contributing to bioactivity. In this work, we developed a composite biologically active coatings based on hybrid molecules obtained by chemical cross-linking of amino acid bisphosphonates with a linear tripeptide RGD, in combination with inorganic porous sublayer created on titanium by plasma electrolytic oxidation (PEO). After the addition of organic molecules, the PEO coated surface gets nobler, but corrosion currents increase. In vitro studies on proliferation and viability of fibroblasts, mesenchymal stem cells and osteoblast-like cells showed the significant dependence of the molecule bioactivity on the structure of bisphosphonate anchor and the linker. Several RGD-modified bisphosphonates of β-alanine, γ-aminobutyric and ε-aminocaproic acids with BMPS or SMCC linkers can be recommended as promising candidates for further in vivo research.

Highlights

Traumatology and orthopedics generate high demand in implants for osseosynthesis, and, according to market forecasts, this demand will increase due to the spread of extreme activities and the aging of the population
We found that carrying out the synthesis at elevated temperature (85–90 ◦ C) decreases the reaction time to 4–5 h, and, along with the separation of the products at pH = 6, increases the resulting yield of the amino bisphosphonates up to 85–89%
We have synthesized a set of RGD-derivatives of amino bisphosphonates, obtained from β-alanine, γ-aminobutyric and ε-aminocaproic acids, containing various linkers (BMPS, EMSC, SMCC) and used them as organic top coatings on porous plasma electrolytic oxidation (PEO) layer on titanium

Summary

Introduction

Traumatology and orthopedics generate high demand in implants for osseosynthesis, and, according to market forecasts, this demand will increase due to the spread of extreme activities and the aging of the population. Various biomimetic approaches that ensure the biocompatibility of the implants are developed [1] As a rule, they suggest changes in the architecture and composition of the surface layer so that the devices gain the properties of the bone tissue and cell membranes. Molecules 2020, 25, 229 the human bone and by introduction of organic molecules containing functional fragments actively interacting with the proteins of the extracellular matrix (ECM). These approaches should provide both biomechanical and biochemical compatibility of the implants, their corrosion resistance, and, should successfully initiate the metal device osseointegration into the bone tissue

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