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Effectiveness of Antibacterial Surfaces in Osseointegration of Titanium Dental Implants: a Systematic Review

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Effectiveness of Antibacterial Surfaces in Osseointegration of Titanium Dental Implants: a Systematic Review antibiotics Review Effectiveness of Antibacterial Surfaces in Osseointegration of Titanium Dental Implants: A Systematic Review Nansi López-Valverde 1 , Bruno Macedo-de-Sousa 2 , Antonio López-Valverde 1,* and Juan Manuel Ramírez 3 1 Department of Surgery, Instituto de Investigación Biomédica de Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain; [email protected] 2 Institute for Occlusion and Orofacial Pain, Faculty of Medicine, University of Coimbra, Polo I-Edifício Central Rua Larga, 3004-504 Coimbra, Portugal; [email protected] 3 Department of Morphological Sciences, University of Cordoba, Avenida Menéndez Pidal S/N, 14071 Cordoba, Spain; [email protected] * Correspondence: [email protected] Abstract: Titanium (Ti) dental implant failure as a result of infection has been established at 40%, being regarded as one of the most habitual and untreatable problems. Current research is focused on the design of new surfaces that can generate long-lasting, infection-free osseointegration. The purpose of our study was to assess studies on Ti implants coated with different antibacterial surfaces, assessing their osseointegration. The PubMed, Web of Science and Scopus databases were electronically searched for in vivo studies up to December 2020, selecting six studies that met the inclusion criteria. The quality of the selected studies was assessed using the ARRIVE (Animal Research: Reporting of In Vivo Experiments) criteria and Systematic Review Center for Laboratory animal Experimentation’s (SYRCLE’s) risk of bias tool. Although all the included studies, proved greater osseointegration Citation: López-Valverde, N.; capacity of the different antibacterial surfaces studied, the methodological quality and experimental Macedo-de-Sousa, B.; models used in some of them make it difficult to draw predictable conclusions. Because of the López-Valverde, A.; Ramírez, J.M. Effectiveness of Antibacterial foregoing, we recommend caution when interpreting the results obtained. Surfaces in Osseointegration of Titanium Dental Implants: A Keywords: titanium dental implants; antibacterial coating surfaces; osseointegration Systematic Review. Antibiotics 2021, 10, 360. https://doi.org/10.3390/ antibiotics10040360 1. Introduction Academic Editor: Catherine Mullié More than 50 years ago, Bränemark described the process of osseointegration as “a direct structural and functional connection between ordered, living bone and the surface Received: 2 March 2021 of a load-carrying implant”. This researcher proved that an implant’s titanium (Ti) oxide Accepted: 26 March 2021 coating could fuse to living bone and that Ti and bone would be impossible to separate Published: 28 March 2021 without fracturing [1,2]. The process of osseointegration basically consists of an anchoring mechanism through Publisher’s Note: MDPI stays neutral which Ti effectively bonds with the living bone, remaining under all normal load condi- with regard to jurisdictional claims in tions and providing prostheses with long-term clinical stability [3,4]. Despite this, direct published maps and institutional affil- bone-to-implant contact could be indicative of a lack of systemic or local response to the iations. implant’s surface and, therefore, osseointegration would involve a biologically negative tissue response [5]. Nevertheless, as reported in earlier publications [6], osseointegration remains a complex and unknown process that depends on certain systems such as the immune system and the autonomic nervous system. Copyright: © 2021 by the authors. Although postoperative infections after implant surgery are uncommon, some fail- Licensee MDPI, Basel, Switzerland. ures are due to infection at the moment of placement or in the following days [7], with a This article is an open access article prevalence of around 12% [8]. Moreover, even completely sterilized Ti implants are prone distributed under the terms and to bacterial infections, sometimes as a result of the host’s defenses being compromised and conditions of the Creative Commons others due to the questionable antibacterial properties of Ti that have been reported in cer- Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ tain studies [9]. Bacterial infections around implant surrounding tissue (peri-implantitis), 4.0/). whose criteria were established at the World Workshop on the Classification of Periodontal Antibiotics 2021, 10, 360. https://doi.org/10.3390/antibiotics10040360 https://www.mdpi.com/journal/antibiotics Antibiotics 2021, 10, 360 2 of 16 in certain studies [9]. Bacterial infections around implant surrounding tissue (peri-implan- Antibiotics 2021, 10, 360 2 of 16 titis), whose criteria were established at the World Workshop on the Classification of Per- iodontal and Peri-implant Diseases and Conditions [10], are one of the most common and untreatable problems associated with Ti dental implants, compromising their integration andand Peri-implantdestroying their Diseases stability, and leading Conditions to eventual [10], are failure one of [11]. the most common and untreat- able problemsThis, alongside associated the need with of Tiearly dental osseointeg implants,ration, compromising is one of the theirreasons integration why research and destroyingin recent decades their stability, has focused leading more to eventualon implan failuret surfaces [11]. than on the geometry and design of theThis, devices, alongside the aim the needbeing of to early achieve osseointegration, safer and longer is one osseointegration of the reasons whyperiods, research after inthe recent testing decades and description has focused of moredifferent on implant dental implant surfaces coatings than on with the geometry antibacterial and proper- design ofties the such devices, as different the aim molecules, being to achievemetals, saferminerals, and longerantibiotics osseointegration and antiseptics, periods, among after oth- theers testing[12–19]. and Figure description 1 illustrates of different the increase dental in implantthe number coatings of publications with antibacterial that has prop-taken ertiesplace suchin recent as different years. molecules, metals, minerals, antibiotics and antiseptics, among othersThe [12 –purpose19]. Figure of 1this illustrates study thewas increase to assess, in thein vivo, number different of publications endosseous that hasTi devices taken placecoated in with recent a variety years. of antimicrobial agents aimed at enhancing osseointegration. FigureFigure 1.1. Increase in in publications publications in in recent recent years, years, with with the the keywords keywords “Ti “Ti dental dental implants” implants” AND AND “antibacterial“antibacterial surfaces surfaces coating” coating” Source: Source: Web Web of of Science. Science. 2. ResultsThe purpose of this study was to assess, in vivo, different endosseous Ti devices coated2.1. Search with Results a variety and of Study antimicrobial Description agents aimed at enhancing osseointegration. 2. ResultsUntil December 2020, a total of 30 studies were selected and independently assessed 2.1.by two Search reviewers. Results and A Studytotal of Description 6 studies were included in the systematic review (Figure 2 Flowchart). 212 implants coated with 6 different antibacterial surfaces were assessed. No Until December 2020, a total of 30 studies were selected and independently assessed meta-analysis was conducted because of the scarcity and heterogeneity of the studies. by two reviewers. A total of 6 studies were included in the systematic review (Figure2 Flowchart). 212 implants coated with 6 different antibacterial surfaces were assessed. No meta-analysis was conducted because of the scarcity and heterogeneity of the studies. Antibiotics 2021, 10, 360 3 of 16 Antibiotics 2021, 10, 360 3 of 16 Figure 2. Flowchart. Figure 2. Flowchart. 2.2. Description of the Characteristics of the Studies 2.2. Description of the Characteristics of the Studies Tables1–3 provide a general description of the characteristics of the included studies. The studiesTables used 1–3 provide 4 experimental a general models description (rabbit of [20 the], mouse characteristics [21], rat [of22 the] and included dog [19 ,studies.23,24]). SampleThe studies sizes variedused 4 betweenexperimental 3 [19] andmodels 36 animals(rabbit [[20],22]. Twomouse studies [21], [19rat,20 [22]] used and metal dog coatings[19,23,24]). (Ta, Sample Sr), two sizes used varied antibiotic between coatings 3 [19] (DC, and BC) 36 andanimals two used[22]. Two [23,24 studies] rhBMP. [19,20] The longestused metal monitoring coatings period (Ta, Sr), was two 8 used weeks antibiotic [20,21,23 coatings,24]. All (DC, the studies BC) and reported two used on [23,24] bone formationrhBMP. The around longest implants, monitoring the most period used was measurement 8 weeks [20,21,23,24]. method being All the BIC studies [20–24 reported]. Only twoon bone of the formation studies assessed around antibacterialimplants, the activity most used of coating measurement surfaces method [19,22]. being BIC [20– 24]. Only two of the studies assessed antibacterial activity of coating surfaces [19,22]. Antibiotics 2021, 10, 360 4 of 16 Table 1. Characteristics of included studies. Location of Animal Model Studies Implant Follow-Up Analysis Methods Conclusions (n) Placement - Micro-CT. - Bone volume (BV). The SLA-Ta (Tantalum) surface showed excellent Mandible - Bone Mineral Density Beagle dog antibacterial activity against (premolars (BMD). Zhang et al. [19] model 4 weeks Porphyromonas gingivalis
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