Electrochemically deposited antimicrobial hydroxyapatite coatings
Mokabber, Taraneh
DOI:
10.33612/diss.132596200
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Publication date: 2020
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Mokabber, T. (2020). Electrochemically deposited antimicrobial hydroxyapatite coatings. University of Groningen. https://doi.org/10.33612/diss.132596200
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Introduction
Summary
Metallic implants have been extensively used in dentistry and orthopedics for many decades. The ever-remaining challenges associated with the use of these implants are the improvement of biocompatibility and bioactivity, along with inhibiting bacterial infection. In this introductory chapter, silver-containing calcium phosphate coatings are introduced as a potential development to tackle the eminent challenges since biocompatibility and antimicrobial activity often have conflicting functions as the antimicrobial approach might also be toxic to tissue cells. The background and motivation are provided and at the end of the chapter are coupled to the various studies presented in this thesis.
1.1 Biomedical implants
In recent years, the use of biomedical implants and devices has seen an increasing trend. Among all implants, orthopedic and dental implants have the largest market size [1,2]. It is estimated that by 2030, in the United States, the demand for primary total hip and knee replacements will grow by 174% and 673% respectively, since 2005. This industry is expected to reach an estimated market value of $33 billion by 2022 [3]. Also dental implants display an increase in number of placements with approximately 2 million dental implants being placed each year [4]. The majority of these implants are remarkably successful, however, still some of the implants and replacements fail due to the biological factors (infection) or biomechanical factors (integrations) [5]. Hence, the development and improvement of biomedical implants are a growing research field.
Different kinds of materials are used in biomedical industry, such as polymers, ceramics, metals, composites and natural products. The materials utilized for implants, especially load bearing implants, should possess some critical properties, for example, a combination of high strength and low modulus, excellent biocompatibility, high corrosion resistance in the biological environment, superior fatigue and wear resistance, and being nontoxic. Providing all these properties by metallic materials leads to use metals more frequently than other materials [2,6].
The metals that have been used for implants include 316L stainless steels, cobalt chromium alloy, and titanium (Ti) and its alloys. Stainless steel has poor wear resistance in comparison with other metals and it may contain nickel, which can cause allergy. Similar to stainless steel, cobalt alloys generally contain nickel and chromium that make these alloys allergenic too. Besides, both 316L stainless steel and cobalt chromium alloys have much higher modulus than bone, resulting in insufficient stress transfer to the bone. As a result, after some years of implantation, the implant may loosen due to bone resorption [2,6]. Consequently, amongst the materials available for implant applications, titanium and titanium alloys are more appropriate than other metals because of their suitable modulus (which is not too high and too low, varying from 50 to 110 GPa), high mechanical strength, good fatigue strength, low density, excellent corrosion resistance, biocompatibility with bone tissue, and low toxicity. Endued with these outstanding properties, titanium has been extensively used in various clinical implantation devices, including bone fixation, knee joint replacement, hip replacement, dental implants, prostheses, cardiovascular implants and maxillofacial and craniofacial treatments (Figure 1-1) [2,6–8].
Figure 1-1 Implants in human body [8].
1.2 Introducing bioactive coatings
Despite all its favorable attributes, titanium exhibits rather poor bioactivity and osteoconductivity, which are defined as the abilities to grow bone on the surface of the implant. Even if the conventional titanium implant is stably anchored by the bone around it, in many clinical cases of implants, an osseoinductive behavior of the implant surface is required specifically if fast healing is demanded. Osseoinduction is the process regularly seen in any type of bone healing procedure. In osseoinduction process, immature cells recruited to stimulate and develop the preosteoblasts [9,10]. In order to improve the osseoinductivity of metallic implants, some surface modifications are suggested for promoting direct chemical bonding between the implant and the host bone tissue. One approach is depositing calcium phosphate (Ca-P) ceramic coatings on the implant surface. Calcium phosphate compounds have excellent biocompatibility due to their compositional similarity to natural bone mineral and exhibit a surface chemistry that promotes the formation of bone-like
hydroxyapatite on its surface. The ability of Ca-P ceramics to improve osteoconductivity and bone-tissue integration and also have very low toxicity makes them favorable among other coatings for metallic implants [11–13]. Ca-P compounds have several types of crystalline structures, some of the most important calcium phosphates structures are presented in Table 1-1. Each phase has a different crystallographic structure with different Ca/P ratio as well as variable degradability in biological environments [14].
Table 1-1 Main calcium phosphates salts [14].
Among these phases, hydroxyapatite has been used frequently as a coating for metallic implants, since it is thermodynamically more stable and is the main component of bone tissues. Hydroxyapatite is a crystalline phase with the stoichiometric formula of Ca10(PO4)6(OH)2. The crystal structure of hydroxyapatite
is hexagonal with a space group p63/m, and its unit cell parameters are a(b)=0.9430 nm and c=0.6891 nm [14,15]. The composition and atomic arrangement of c axis and
a(b) axis in hydroxyapatite structure are completely different from each other. The c
planes are mainly occupied by phosphate or hydroxide groups and negatively charged whereas the a(b) planes are occupied by calcium ions and positively charged. Therefore, these planes exhibit different properties. As a consequence, c axis and a(b) axis are preferred in long bones and tooth enamel, respectively (Figure 1-2). Therefore, according to its biomedical applications, it is expected to have a preferred orientation which can be achieved via different processing technologies during syntheses [15,16].
Name Symbol(s) Formula Ca/P
Monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2.H2O 0.5
Monocalcium phosphate anhydrous (MCPA) Ca(H2PO4)2 0.5
Dicalcium phosphate dihydrate (Brushite) (DCPD) CaHPO4.2H2O 1.0
Dicalcium phosphate anhydrous (Monetite) (DCPA) CaHPO4 1.0
Octacalcium phosphate (OCP) Ca8(HPO4)2(PO4)4.5H2O 1.33
α-Tricalcium phosphate (α-TCP) Ca3(PO4)2 1.5
β-Tricalcium phosphate (β-TCP) Ca3(PO4)2 1.5
Amorphous calcium phosphate (ACP) Cax(PO4)y.nH2O 1.2-2.2
Figure 1-2 (a) Orientation of HA crystals in long bone and tooth enamel, and (b) model of HA crystal growth [15, adapted with permission].
1.3 Microbial infection of implants and solutions
New generation implant fabrication needs not only the development of new coatings on metallic implants to fulfill the biocompatibility and bioactivity, but also the prevention of implant-associated infections which are a severe complication in orthopedic surgery [9]. Bacterial contamination is usually caused by the adhesion and colonization of bacteria on the implant surface, which results in the failure of surgical operations. Implant-associated infections are difficult to treat because the bacteria that cause these infections live in mature biofilms and develop resistance to antibiotic treatments. Therefore, for an infected implant, the removal and replacement are the only effective treatments which cause increased health care costs [17,18].
In order to prevent the initial implant-associated infection, several surface modifications with antimicrobial agents have been proposed [19]. A number of researchers have focused on developing silver-containing hydroxyapatite coatings to provide antimicrobial activity while maintaining the bioactivity of the implant. Silver (Ag) is a well-known antimicrobial agent and is effective against a broad spectrum of
bacterial strains (more than 650 pathogens) while being relatively low in toxicity towards mammalian cells. Silver as ions, compounds, and nanoparticles has been increasingly used for infection treatment due to its excellent antimicrobial properties [20–22].
The antimicrobial mechanism of silver is not clearly understood yet. However, studies have shown that silver can adsorb on the cell wall of the bacteria, interact with thiol group proteins, form pits in the cell membrane, penetrate the cytoplasm and eventually cause cell death [23–25]. Figure 1-3 illustrates the effect of silver in the hydroxyapatite-silver nanocomposite on E. coli bacteria. As it is shown in transmission electron microscopy (TEM) images, the silver nanoparticles attach to the cell wall of E. coli and rupture the cell membrane due to the formation of pits followed by dell death. These results are in complete agreement with the above mentioned mechanism of antimicrobial action of silver [23].
Figure 1-3 TEM images of hydroxyapatite–silver nanocomposite treated GFP E. coli: (a) the E. coli with damaged cell wall and (b) presence of Ag nanoparticles on the E. coli cell wall [23, adapted with permission].
In conclusion, incorporation of silver into hydroxyapatite coatings provides a great potential application in coatings for metallic implants to prevent implant-associated infections while maintaining the bioactivity of the implants. However, when silver is used as an antimicrobial agent in the coatings, important factors such as minimization of the cytotoxic effects and the ability for long-term sustained antimicrobial action must be considered. It has been reported that the higher concentration of silver in the material results in better antimicrobial effect but with increasing toxicity to mammalian cells. It is therefore necessary to optimize the silver
the biocompatibility [26,27]. Even though many studies have already been done, further investigations are still required to optimize the silver concentration in such biomedical coatings for better performance.
1.4 Electrochemical deposition
Silver-containing calcium phosphate coatings can be synthesized via different techniques, such as biomimetic deposition [28], plasma spraying [21,29], magnetron sputtering [30], sol-gel process [31], and electrochemical deposition (ECD) [32]. The most widely used method to deposit coatings on the implants is plasma spraying. However, this method has some disadvantages, for instance, the extremely high temperature of the operation leads to the deposition of decomposed phases like tricalcium phosphate or amorphous phases. In addition, this method is a line-of-sight process that deposits non-uniform coatings on components with complex shapes and gives low bonding strength at the coating/implant interface [33].
Compared to other methods, the electrochemical deposition technique seems more favorable because of its advantages such as sufficiently low cost, simplicity of performance, low processing temperature and rapid deposition. Moreover, it is not a line-of-sight technique, enabling highly irregularly shaped objects to be coated uniformly. Therefore, depositing silver-containing calcium phosphate coatings via electrochemical deposition is a very promising strategy to improve the performance of implants. The ECD technique depends on numerous parameters such as solution composition, pH, deposition temperature, applied voltage or current density, and additives. These factors can affect the purity, crystallinity, stoichiometry, morphology and mechanical properties of the deposited coatings. In order to get optimal conditions for silver-containing calcium phosphate coatings with desirable properties the effect of these parameters on crystallization behavior needs comprehensive investigation [34–36].
1.5 Outline and aim of this thesis
The aim of the research in this thesis is to develop bioactive and antimicrobial coatings on titanium for biomedical applications. To do so, silver-containing calcium phosphate coatings were synthesized via electrochemical deposition and their chemical, mechanical, and biological properties were investigated. The focus was on the interplay between the effect of different deposition parameters and the chemical and physical properties of the coatings. The project aimed at getting fundamental insight into the crystal growth mechanism of electrodeposited calcium phosphate coatings and its influence on mechanical and biological properties of the coatings. In addition, the antimicrobial mechanism and biocompatibility of the silver-containing
calcium phosphate coatings were systematically investigated. The following is the detailed outline of the chapters of this thesis:
A literature overview on bioactive and antimicrobial coatings applied to titanium implants is presented in chapter 2. It includes an introduction for metallic implants and different modification that are applied to improve their properties. Calcium phosphate coatings as bioactive and biocompatible coatings are introduced and the electrochemical deposition as a most appropriate deposition method for these coatings is discussed. Finally, the properties, synthesizing methods and evaluation of silver-containing calcium phosphate coatings are discussed.
The effect of electrodeposition parameters on the phase composition and microstructure of the calcium phosphate coatings is explored in chapter 3. The parameters such as applied voltage, applied current density, electrolyte composition, deposition temperature and time are optimized according to the morphology and the purity of the coatings.
In chapter 4, the calcium phosphate coatings are characterized to identify the main mechanisms responsible for the nucleation and growth of electrodeposited calcium phosphate crystals that lead to different morphologies and crystallographic orientations.
The mechanical and biological properties of the electrodeposited calcium phosphate coatings with different morphologies are investigated in chapter
5. The micro-scratch test is employed to evaluate the adhesion strength of
the coatings, and the response of osteosarcoma cells (SaOs) is studied to investigate the effect of the surface morphology on cell adhesion, viability, and proliferation.
In chapter 6, synthesized silver-containing calcium phosphate coatings are characterized regarding their microstructure, chemical composition, morphology and the chemical states of silver in the coatings. A detailed analysis of the silver release rate and antimicrobial mechanism are also presented in this chapter. Staphylococcus aureus and osteosarcoma cells (SaOs) are used to evaluate the antimicrobial properties and biocompatibility of the coatings, respectively.
Chapter 7 summaries the content of this thesis, and gives an outlook of
possible future research directions related with the scope of this work and the advanced biomaterials developed in this thesis.
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