Protein adsorption/desorption dynamics on Ca-enriched titanium surfaces: biological implications

Raul Izquierdo,Mariló Gurruchaga,Mikel Azkargorta,Eduardo Anitua,Cristina Martinez-Ramos,Iñaki García-Arnáez,Andreia Cerqueira,Ricardo Tejero,Julio Suay,Seda Ozturan,Isabel Goñi,Francisco Romero-Gavilán,Félix Elortza

doi:10.1007/s00775-021-01886-4

Abstract

Calcium ions are used in the development of biomaterials for the promotion of coagulation, bone regeneration, and implant osseointegration. Upon implantation, the time-dependent release of calcium ions from titanium implant surfaces modifies the physicochemical characteristics at the implant–tissue interface and thus, the biological responses. The aim of this study is to examine how the dynamics of protein adsorption on these surfaces change over time. Titanium discs with and without Ca were incubated with human serum for 2 min, 180 min, and 960 min. The layer of proteins attached to the surface was characterised using nLC-MS/MS. The adsorption kinetics was different between materials, revealing an increased adsorption of proteins associated with coagulation and immune responses prior to Ca release. Implant–blood contact experiments confirmed the strong coagulatory effect for Ca surfaces. We employed primary human alveolar osteoblasts and THP-1 monocytes to study the osteogenic and inflammatory responses. In agreement with the proteomic results, Ca-enriched surfaces showed a significant initial inflammation that disappeared once the calcium was released. The distinct protein adsorption/desorption dynamics found in this work demonstrated to be useful to explain the differential biological responses between the titanium and Ca-ion modified implant surfaces.Graphic abstract

Highlights

Bivalent cationic ions, such as calcium, have been studied as key factors to improve the bone regeneration process around biomaterials [1, 2]
Calcium mediates the binding of the platelet membrane phospholipids to factor Xa and factor IXa, which are required for the operation of the tenase and prothrombinase complexes
Doe et al [9] found that acid-etched pure titanium implants with calcium ion surface modification showed remarkably high osteogenic activity and high stability in osseous tissue

Summary

Introduction

Bivalent cationic ions, such as calcium, have been studied as key factors to improve the bone regeneration process around biomaterials [1, 2]. Calcium mediates the binding of the platelet membrane phospholipids to factor Xa and factor IXa, which are required for the operation of the tenase and prothrombinase complexes. These complexes convert prothrombin into thrombin (factor IIa), which triggers fibrin polymerisation [4]. Ca2+ can favour osteoblast proliferation, mineralization, and extracellular matrix mineralization [5] This key role of calcium in bone tissue regeneration has turned this element into an interesting option in the development of biomaterials [6]. Calcium on the implant surface could enhance the rate of protein adsorption, acting as a protein-binding site and conditioning the type of protein that adheres to the implant [12]

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