From manufacturers to clinicians, the release of dental implant particles can no longer be ignored

IF 3.7 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Clinical Implant Dentistry and Related Research Pub Date : 2024-02-19 DOI:10.1111/cid.13309
Fadi N. Barrak BDS, FDSRCS, MBBS, DipImpDent, RCSEd, FHEA, PhD, Siwei Li PhD
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Some implants fail due to a variety of reasons including peri-implantitis, lack of osseointegration, material wear and corrosion, and hypersensitivity.<span><sup>5-7</sup></span></p><p>For any implant system on the market, a series of complex and stringent standards need to be met during various stages including in vitro testing, in vivo and clinical trials, and manufacturing. Table 1 summarises the major standards dental implant companies follow.</p><p>Authors searched publicly available compliance documentations published by major dental implant companies, including BioHorizons, Dentsply Sirona, Nobel Biocare, Osstem, and Straumann. While all companies demonstrated compliance with ISO 13485 (Medical device quality management system) during the design, development, manufacture, and distribution of dental implants (and related components), information on how tests were conducted in accordance to above-mentioned ISO standards was not readily available to public. In addition, standards for biological evaluation of medical devices such as ISO 10993 permits the use of whole implant, and thus the biological implications of free Ti-based particles and metallic ions can be overlooked.</p><p>In patients that had dental implants, Ti particles, as a product of wear and/or degradation, have been detected in both intra- and extra-oral tissues. Ti particles have been found in peri-implant bone and/or soft tissues, submucosal plaque, and in distant lymph nodes in human pilot studies.<span><sup>13-15</sup></span> Ti particles have also been shown in both animal and human studies to be present in lungs, kidneys, livers, spleen, and abdominal lymph nodes, with some suggesting that particles were transported in the bloodstream by phagocytic cells and plasma proteins to these distal organs.<span><sup>16-18</sup></span> Authors' own ex vivo study has demonstrated that metallic nano- and micro-sized particles were released from dental implants immediately after placement.<span><sup>19</sup></span> They can be seen embedded in peri-implant bone tissue as well as internalized by cells such as human gingival fibroblasts and macrophages. Another study involving human biopsies has also reported localization of Ti particles in macrophages and epithelium cells.<span><sup>20</sup></span> It has been suggested that in cells with phagocytized Ti particles, alterations to basic cell mechanism may occur and subsequently lead to reactive lesions such as pyogenic and/or peripheral giant cell granulomas.<span><sup>21, 22</sup></span> Peri-implantitis is a plaque-associated pathological condition occurring in tissues around dental implants.<span><sup>23</sup></span> It is characterized by inflammation in the peri-implant mucosa and subsequent progressive loss of surrounding supporting bone in which the implant is anchored. Peri-implantitis sites had higher concentrations of Ti particles in comparison to healthy implant sites,<span><sup>24-28</sup></span> while authors acknowledge that there is no definitive evidence, and there is a strong association between implant particle release and peri-implantitis.</p><p>The most common feasible causes of Ti particle release are friction during implant placement procedures, implant surface corrosion, and fretting phenomena at the implant-abutment interphase.<span><sup>29</sup></span> The use of dental hygiene products and antiseptic agents such as fluoride and chlorhexidine have been linked with alterations to the implant surface topography and increased corrosion.<span><sup>30, 31</sup></span> In addition, implant debridement procedures, for example, surface cleaning with mechanical and/or chemical means, used during implant maintenances and treatment of peri-implantitis, such as implantoplasty, were also reported to be the causes of particle release.<span><sup>25, 32</sup></span> Authors' own ex vivo study has found that the amount of metallic particle and ion release during placement was dependent on both implant material and design, where grade 5 titanium alloy (Ti-6AL-4V) implants resulted in more release compared to commercial pure (grade 4) or Roxolid® (Ti-15Zr, a Ti alloy composed of ~15% zirconium) implants.<span><sup>19</sup></span> In an in vitro study that investigated particle release due to frictional wear, it was also reported that wear signs were evident in all implant-abutment couplings (grade 4 or Roxolid® implants paired with Ti or Zr abutments).<span><sup>33</sup></span> More interestingly, it was found that larger particles were generated in Roxolid® with Ti or Zr abutment pairings in comparison to grade 4 implants. These findings emphasize the need of careful pre-manufacturing evaluations of the implant materials and designs as there is increasing evidence of potential risks of these wear particles.</p><p>As the use of Ti and its alloy increases, concerns over their safety are also increasing as the number of research and reports focusing on Ti toxicity showed a rapid upward trend in recent years.<span><sup>34</sup></span> Both micro- and nano-sized particles can be generated during an implant's life span.<span><sup>19, 32, 34</sup></span> There is evidence that TiO<sub>2</sub> nanoparticles are associated with cellular DNA damage and pro-inflammatory effects.<span><sup>35, 36</sup></span> It has been reported that the TiO<sub>2</sub> nanoparticles could adsorb CXCL8 (and IFN-γ), clinically relevant pro-inflammatory chemokines, thus resulting in the disruption of neutrophil chemotaxis and local inflammatory mediator concentration and subsequently reduced inflammatory response.<span><sup>36</sup></span> Particle release as an inflammation catalyst mechanism is an emerging concept in dental medicine that may help explain the pathogenesis of peri-implantitis.<span><sup>27, 28, 37, 38</sup></span></p><p>Implant losses can be associated with inflammatory complications due to Ti particles.<span><sup>15, 39</sup></span> Peri-implant diseases can be peri-implantitis or peri-implant mucositis, which are characterized by the presence or the lack of peri-implant bone loss, respectively. The general consensus is that peri-implant mucositis is inflammatory disease involving mucosa only, whereas peri-implantitis sites extend to supporting bone.<span><sup>23</sup></span> Souza and colleagues demonstrated that Ti particles affected biofilm composition, increasing population of four bacterial species (<i>Streptococcus anginosus</i>, <i>Prevotella nigrescens</i>, <i>Capnocytophaga sputigena</i>, and <i>Actinomyces israelli</i>), while Ti ions resulted in a higher level of pathogens from disease-associated complex as well as a reduction of health-associated complex.<span><sup>40</sup></span> This suggests Ti particles and ions may encourage the growth of peri-implant pathogenic species, resulting in subsequent microbial dysbiosis and eventually peri-implantitis.</p><p>While many tests can be performed to determine parameters such as implant surface topography, composition, and their effects on adhesion, proliferation, and differentiation of various clinically relevant cell populations, suffice it to say that the current setups in accordance to ISO and regulatory bodies do not reflect the extremely complex physiological microenvironment surrounding an implant. More importantly, the effects of Ti particle and metallic ion released from implants are often overlooked by implant companies and clinicians placing the implants. This clearly indicates a need of awareness in the field of implant dentistry as well as a reliable testing protocol that yields highly reproducible and translatable results with regards to the biological response of patients after implantation.</p><p>Some manufacturers and independent organizations have already taken steps to carry out additional standardized tests in addition to those required by regulatory bodies such as the U.S. Food and Drug Administration (FDA) and European health, safety, and environmental protection standards (CE marking). CleanImplant Foundation, for example, utilizes scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (EDS) in a clean room environment (according to Class 100 US Federal Standard 209E, Class 5 DIN EN ISO 14644-1) to assess surface homogeneity and contaminations of implants during manufacturing and packaging process.<span><sup>41</sup></span> While this is an important development in the field of Implant Dentistry to acknowledge the risk of adverse effects caused by “impurities” such as Ti particles as well as organic particles originated from manufacturing and/or packaging, further biological tests and a more stringent threshold should be applied. CleanImplant argued that single organic particles smaller than 50 μm in diameter were considered less damaging than numerous particles, with a maximum of 30 particles along the circumference of the implant.<span><sup>41</sup></span> In addition, major plaque-like organic contaminants exceeding the size of 50 μm and PTFE particles, presumably originating from Teflon molds used during implant production, were considered unacceptable.<span><sup>41</sup></span> There are studies reporting the density of Ti particles to be as high as 40 million per mm<sup>3</sup> of tissue.<span><sup>27</sup></span> It should be noted however, that there may be differences in the adverse effects of impurities from defective manufacturing and particle release from appropriately manufactured implants. Further studies are required.</p><p>While some clinical/human studies, for example, by Rakic and colleagues,<span><sup>42</sup></span> argued that there is no clear evidence of direct pathological effects of implant particles, particles were identified in all peri-implantitis samples in this study, while another reported presence of particles in 90% peri-implant soft tissue biopsies from patients diagnosed with peri-implantitis.<span><sup>43</sup></span> Authors believe the prevalence of the particles depicts a strong association between Ti particles and peri-implant disease. As mentioned above that both nanometer- and micrometer-sized Ti particles can be detected in peri-implant tissues.<span><sup>19, 26, 44</sup></span> The size of particles can vary depending on the implant size, design, and material.<span><sup>19, 33</sup></span> Authors acknowledge that it is currently unclear which particle configuration (e.g. size and surface chemistry) and location of distribution results in unfavorable biological response. It is therefore important to apply a standardized set of testing methods to each variation of the same implant system. The biological effects of wear particles, especially nanometer-sized particles, remain unclear and debatable. Some have observed positive antibiofilm properties with either Ti nanoparticles alone, or in combination with other metal nanoparticles, leading to suggestions that these nanoparticles can protect against peri-implantitis pathogens.<span><sup>45, 46</sup></span> Ti nanoparticles have been proposed as a commercially viable anti-plaque and anti-biofilm strategy in products such as tooth pastes and mouthwashes.<span><sup>47</sup></span> Others on the other hand, have reported adverse effects such as induction of apoptosis, genotoxicity, collagen, and lipid deformation as well as alveolar epithelial metaplasia.<span><sup>39, 48, 49</sup></span> It has been reported that nano- and micro-sized Ti particles are associated with the activation of inflammatory response and the release of pro-inflammatory cytokines such as TNF-α and IL-1β.<span><sup>50, 51</sup></span> In addition, Ti particles have been shown to induce M1 macrophage phenotype polarization and associated bone resorption.<span><sup>52</sup></span> Ti nanoparticles have been reported to initiate the TLR4 (toll-like receptor 4)-dependent pathway and the subsequent overproduction of MUC5B (mucin 5B), which is involved in the inflammatory response in human airways.<span><sup>53</sup></span> Although the body of evidence suggests that the biological effects of implant (nano)particles is inflammatory, more specific toxological research is needed and biomarker assays should be incorporated during the evaluation process of an implant.</p><p>Another possible cause of implant failure can be attributed to allergic reactions to titanium, albeit there is limited evidence. Hypersensitivity reactions such as erythema, eczema, necrosis, and bone loss due to Ti dental implants have been reported in some studies.<span><sup>7, 54, 55</sup></span> Concerns of adverse effects of Ti and its alloys have led to the research and development of alternative implant materials. One example is zirconia and polyaryletherketone (PEEK), which have gained increasing interest as a material in dental applications mainly due to its good biocompatibility and biomechanical characteristics.<span><sup>56-58</sup></span> However, further investigations are required before such material can become a viable commercial and clinical alternative to Ti. This commentary focused exclusively on titanium-based metal implants, and authors do acknowledge there is also propensity for particle release and accumulation from implants made with alternative materials.<span><sup>27</sup></span></p><p>Ti-based dental implants currently have an undisputed high survival rate clinically and will continue to be successful commercially. However, attention now must be placed on the potential adverse effects associated with Ti implants, in particular, their wear particles. A new set of standards for the evaluation of biological response to implant wear particles and metallic ions needs to be developed with the aim to increase the predictive power of preclinical assessment of materials and dental implants. These testing data should be readily available such that clinicians as well as patients are aware of the biological and mechanical implications of materials used in dental implants. Dental implant providers, be it the manufacturers or the clinicians placing the implants, need to be aware of these potential risks and the need for additional testing standards as they inevitably bear the responsibility of the products used and treatments provided to the general public.</p><p>FB contributed to the conception, drafting, critical revision, and approval of article. SL contributed to the drafting and critical revision of article.</p><p>The authors declare no conflicts of interest.</p>","PeriodicalId":50679,"journal":{"name":"Clinical Implant Dentistry and Related Research","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cid.13309","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Implant Dentistry and Related Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cid.13309","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
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Abstract

Dental implants offer a widely accepted and viable long-term treatment option for patients with missing teeth.1, 2 Since the discovery of its biocompatibility and capability of osseointegration, titanium (Ti) and its alloys have become the gold standard and most widely used in implant dentistry.3, 4 There are implants made with other materials, this opinion paper will focus on titanium-based implants. While such implants have proven to be highly reliable and have high success rates, it is not without complications. Some implants fail due to a variety of reasons including peri-implantitis, lack of osseointegration, material wear and corrosion, and hypersensitivity.5-7

For any implant system on the market, a series of complex and stringent standards need to be met during various stages including in vitro testing, in vivo and clinical trials, and manufacturing. Table 1 summarises the major standards dental implant companies follow.

Authors searched publicly available compliance documentations published by major dental implant companies, including BioHorizons, Dentsply Sirona, Nobel Biocare, Osstem, and Straumann. While all companies demonstrated compliance with ISO 13485 (Medical device quality management system) during the design, development, manufacture, and distribution of dental implants (and related components), information on how tests were conducted in accordance to above-mentioned ISO standards was not readily available to public. In addition, standards for biological evaluation of medical devices such as ISO 10993 permits the use of whole implant, and thus the biological implications of free Ti-based particles and metallic ions can be overlooked.

In patients that had dental implants, Ti particles, as a product of wear and/or degradation, have been detected in both intra- and extra-oral tissues. Ti particles have been found in peri-implant bone and/or soft tissues, submucosal plaque, and in distant lymph nodes in human pilot studies.13-15 Ti particles have also been shown in both animal and human studies to be present in lungs, kidneys, livers, spleen, and abdominal lymph nodes, with some suggesting that particles were transported in the bloodstream by phagocytic cells and plasma proteins to these distal organs.16-18 Authors' own ex vivo study has demonstrated that metallic nano- and micro-sized particles were released from dental implants immediately after placement.19 They can be seen embedded in peri-implant bone tissue as well as internalized by cells such as human gingival fibroblasts and macrophages. Another study involving human biopsies has also reported localization of Ti particles in macrophages and epithelium cells.20 It has been suggested that in cells with phagocytized Ti particles, alterations to basic cell mechanism may occur and subsequently lead to reactive lesions such as pyogenic and/or peripheral giant cell granulomas.21, 22 Peri-implantitis is a plaque-associated pathological condition occurring in tissues around dental implants.23 It is characterized by inflammation in the peri-implant mucosa and subsequent progressive loss of surrounding supporting bone in which the implant is anchored. Peri-implantitis sites had higher concentrations of Ti particles in comparison to healthy implant sites,24-28 while authors acknowledge that there is no definitive evidence, and there is a strong association between implant particle release and peri-implantitis.

The most common feasible causes of Ti particle release are friction during implant placement procedures, implant surface corrosion, and fretting phenomena at the implant-abutment interphase.29 The use of dental hygiene products and antiseptic agents such as fluoride and chlorhexidine have been linked with alterations to the implant surface topography and increased corrosion.30, 31 In addition, implant debridement procedures, for example, surface cleaning with mechanical and/or chemical means, used during implant maintenances and treatment of peri-implantitis, such as implantoplasty, were also reported to be the causes of particle release.25, 32 Authors' own ex vivo study has found that the amount of metallic particle and ion release during placement was dependent on both implant material and design, where grade 5 titanium alloy (Ti-6AL-4V) implants resulted in more release compared to commercial pure (grade 4) or Roxolid® (Ti-15Zr, a Ti alloy composed of ~15% zirconium) implants.19 In an in vitro study that investigated particle release due to frictional wear, it was also reported that wear signs were evident in all implant-abutment couplings (grade 4 or Roxolid® implants paired with Ti or Zr abutments).33 More interestingly, it was found that larger particles were generated in Roxolid® with Ti or Zr abutment pairings in comparison to grade 4 implants. These findings emphasize the need of careful pre-manufacturing evaluations of the implant materials and designs as there is increasing evidence of potential risks of these wear particles.

As the use of Ti and its alloy increases, concerns over their safety are also increasing as the number of research and reports focusing on Ti toxicity showed a rapid upward trend in recent years.34 Both micro- and nano-sized particles can be generated during an implant's life span.19, 32, 34 There is evidence that TiO2 nanoparticles are associated with cellular DNA damage and pro-inflammatory effects.35, 36 It has been reported that the TiO2 nanoparticles could adsorb CXCL8 (and IFN-γ), clinically relevant pro-inflammatory chemokines, thus resulting in the disruption of neutrophil chemotaxis and local inflammatory mediator concentration and subsequently reduced inflammatory response.36 Particle release as an inflammation catalyst mechanism is an emerging concept in dental medicine that may help explain the pathogenesis of peri-implantitis.27, 28, 37, 38

Implant losses can be associated with inflammatory complications due to Ti particles.15, 39 Peri-implant diseases can be peri-implantitis or peri-implant mucositis, which are characterized by the presence or the lack of peri-implant bone loss, respectively. The general consensus is that peri-implant mucositis is inflammatory disease involving mucosa only, whereas peri-implantitis sites extend to supporting bone.23 Souza and colleagues demonstrated that Ti particles affected biofilm composition, increasing population of four bacterial species (Streptococcus anginosus, Prevotella nigrescens, Capnocytophaga sputigena, and Actinomyces israelli), while Ti ions resulted in a higher level of pathogens from disease-associated complex as well as a reduction of health-associated complex.40 This suggests Ti particles and ions may encourage the growth of peri-implant pathogenic species, resulting in subsequent microbial dysbiosis and eventually peri-implantitis.

While many tests can be performed to determine parameters such as implant surface topography, composition, and their effects on adhesion, proliferation, and differentiation of various clinically relevant cell populations, suffice it to say that the current setups in accordance to ISO and regulatory bodies do not reflect the extremely complex physiological microenvironment surrounding an implant. More importantly, the effects of Ti particle and metallic ion released from implants are often overlooked by implant companies and clinicians placing the implants. This clearly indicates a need of awareness in the field of implant dentistry as well as a reliable testing protocol that yields highly reproducible and translatable results with regards to the biological response of patients after implantation.

Some manufacturers and independent organizations have already taken steps to carry out additional standardized tests in addition to those required by regulatory bodies such as the U.S. Food and Drug Administration (FDA) and European health, safety, and environmental protection standards (CE marking). CleanImplant Foundation, for example, utilizes scanning electron microscope (SEM) and energy-dispersive x-ray spectroscopy (EDS) in a clean room environment (according to Class 100 US Federal Standard 209E, Class 5 DIN EN ISO 14644-1) to assess surface homogeneity and contaminations of implants during manufacturing and packaging process.41 While this is an important development in the field of Implant Dentistry to acknowledge the risk of adverse effects caused by “impurities” such as Ti particles as well as organic particles originated from manufacturing and/or packaging, further biological tests and a more stringent threshold should be applied. CleanImplant argued that single organic particles smaller than 50 μm in diameter were considered less damaging than numerous particles, with a maximum of 30 particles along the circumference of the implant.41 In addition, major plaque-like organic contaminants exceeding the size of 50 μm and PTFE particles, presumably originating from Teflon molds used during implant production, were considered unacceptable.41 There are studies reporting the density of Ti particles to be as high as 40 million per mm3 of tissue.27 It should be noted however, that there may be differences in the adverse effects of impurities from defective manufacturing and particle release from appropriately manufactured implants. Further studies are required.

While some clinical/human studies, for example, by Rakic and colleagues,42 argued that there is no clear evidence of direct pathological effects of implant particles, particles were identified in all peri-implantitis samples in this study, while another reported presence of particles in 90% peri-implant soft tissue biopsies from patients diagnosed with peri-implantitis.43 Authors believe the prevalence of the particles depicts a strong association between Ti particles and peri-implant disease. As mentioned above that both nanometer- and micrometer-sized Ti particles can be detected in peri-implant tissues.19, 26, 44 The size of particles can vary depending on the implant size, design, and material.19, 33 Authors acknowledge that it is currently unclear which particle configuration (e.g. size and surface chemistry) and location of distribution results in unfavorable biological response. It is therefore important to apply a standardized set of testing methods to each variation of the same implant system. The biological effects of wear particles, especially nanometer-sized particles, remain unclear and debatable. Some have observed positive antibiofilm properties with either Ti nanoparticles alone, or in combination with other metal nanoparticles, leading to suggestions that these nanoparticles can protect against peri-implantitis pathogens.45, 46 Ti nanoparticles have been proposed as a commercially viable anti-plaque and anti-biofilm strategy in products such as tooth pastes and mouthwashes.47 Others on the other hand, have reported adverse effects such as induction of apoptosis, genotoxicity, collagen, and lipid deformation as well as alveolar epithelial metaplasia.39, 48, 49 It has been reported that nano- and micro-sized Ti particles are associated with the activation of inflammatory response and the release of pro-inflammatory cytokines such as TNF-α and IL-1β.50, 51 In addition, Ti particles have been shown to induce M1 macrophage phenotype polarization and associated bone resorption.52 Ti nanoparticles have been reported to initiate the TLR4 (toll-like receptor 4)-dependent pathway and the subsequent overproduction of MUC5B (mucin 5B), which is involved in the inflammatory response in human airways.53 Although the body of evidence suggests that the biological effects of implant (nano)particles is inflammatory, more specific toxological research is needed and biomarker assays should be incorporated during the evaluation process of an implant.

Another possible cause of implant failure can be attributed to allergic reactions to titanium, albeit there is limited evidence. Hypersensitivity reactions such as erythema, eczema, necrosis, and bone loss due to Ti dental implants have been reported in some studies.7, 54, 55 Concerns of adverse effects of Ti and its alloys have led to the research and development of alternative implant materials. One example is zirconia and polyaryletherketone (PEEK), which have gained increasing interest as a material in dental applications mainly due to its good biocompatibility and biomechanical characteristics.56-58 However, further investigations are required before such material can become a viable commercial and clinical alternative to Ti. This commentary focused exclusively on titanium-based metal implants, and authors do acknowledge there is also propensity for particle release and accumulation from implants made with alternative materials.27

Ti-based dental implants currently have an undisputed high survival rate clinically and will continue to be successful commercially. However, attention now must be placed on the potential adverse effects associated with Ti implants, in particular, their wear particles. A new set of standards for the evaluation of biological response to implant wear particles and metallic ions needs to be developed with the aim to increase the predictive power of preclinical assessment of materials and dental implants. These testing data should be readily available such that clinicians as well as patients are aware of the biological and mechanical implications of materials used in dental implants. Dental implant providers, be it the manufacturers or the clinicians placing the implants, need to be aware of these potential risks and the need for additional testing standards as they inevitably bear the responsibility of the products used and treatments provided to the general public.

FB contributed to the conception, drafting, critical revision, and approval of article. SL contributed to the drafting and critical revision of article.

The authors declare no conflicts of interest.

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从制造商到临床医生,都不能再忽视牙科植入物微粒的释放。
1, 2 自发现钛(Ti)及其合金具有生物相容性和骨结合能力以来,钛(Ti)及其合金已成为种植牙的黄金标准,并在种植牙领域得到了最广泛的应用。虽然这类种植体已被证明非常可靠,成功率很高,但也并非没有并发症。一些种植体失败的原因多种多样,包括种植体周围炎、缺乏骨结合、材料磨损和腐蚀以及过敏。5-7 对于市场上的任何种植体系统,都需要在体外测试、体内和临床试验以及制造等不同阶段达到一系列复杂而严格的标准。表 1 总结了牙科种植公司遵循的主要标准。作者搜索了主要牙科种植公司发布的公开合规文件,包括 BioHorizons、Dentsply Sirona、Nobel Biocare、Osstem 和 Straumann。虽然所有公司都证明在设计、开发、制造和销售牙科植入物(及相关组件)的过程中符合 ISO 13485(医疗器械质量管理体系)的要求,但有关如何根据上述 ISO 标准进行测试的信息并不容易获得。此外,ISO 10993 等医疗器械生物评估标准允许使用整个种植体,因此可能会忽略游离钛基微粒和金属离子对生物的影响。13-15 在动物和人体研究中,钛微粒也被证明存在于肺、肾、肝、脾和腹部淋巴结中,一些研究表明,微粒在血液中被吞噬细胞和血浆蛋白运送到这些远端器官中。作者自己的体内外研究表明,金属纳米级和微米级颗粒在植入牙科种植体后会立即从种植体中释放出来。19 可以看到它们嵌入种植体周围的骨组织中,并被牙龈成纤维细胞和巨噬细胞等细胞内化。另一项涉及人体活组织切片的研究也报告了钛颗粒在巨噬细胞和上皮细胞中的定位情况。20 有研究认为,在被钛颗粒吞噬的细胞中,可能会发生基本细胞机制的改变,随后导致反应性病变,如化脓性和/或周围巨细胞肉芽肿、22 种植体周围炎是发生在牙科种植体周围组织的一种斑块相关病理情况。23 其特征是种植体周围粘膜发炎,随后种植体固定的周围支撑骨逐渐丧失。与健康的种植体部位相比,种植体周围炎部位的钛微粒浓度更高24-28 ,但作者承认目前还没有确切的证据,种植体微粒释放与种植体周围炎之间存在密切联系。造成钛微粒释放的最常见可行原因是种植体植入过程中的摩擦、种植体表面腐蚀以及种植体与基台间的摩擦现象29。29 牙科卫生用品和消毒剂(如氟化物和洗必泰)的使用与种植体表面形貌的改变和腐蚀的增加有关。30, 31 此外,种植体清创程序,如在种植体维护和种植体周围炎治疗(如种植体成形术)过程中使用的机械和/或化学方法进行的表面清洁,据报道也是颗粒释放的原因、32 作者自己的体内外研究发现,植入过程中金属颗粒和离子的释放量取决于种植体的材料和设计,其中 5 级钛合金(Ti-6AL-4V)种植体与商用纯钛(4 级)或 Roxolid® (Ti-15Zr,一种含约 15% 锆的钛合金)种植体相比释放量更多。33 更有趣的是,研究发现与 4 级种植体相比,Roxolid®种植体与 Ti 或 Zr 基台配对时产生的颗粒更大。这些发现强调了对种植体材料和设计进行仔细的生产前评估的必要性,因为有越来越多的证据表明这些磨损颗粒存在潜在风险。 19、26、44 颗粒的大小可能因植入物的大小、设计和材料而异。19、33 作者承认,目前还不清楚哪种颗粒结构(如大小和表面化学性质)和分布位置会导致不利的生物反应。因此,对同一种植体系统的每种变体采用一套标准化的测试方法非常重要。磨损微粒,尤其是纳米级微粒对生物的影响仍不明确,存在争议。有些人观察到纳米钛微粒单独使用或与其他金属纳米微粒结合使用时具有积极的抗生物膜特性,因此认为这些纳米微粒可以防止种植体周围炎病原体的感染。39, 48, 49 有报告称,纳米和微小尺寸的钛粒子与炎症反应的激活和促炎细胞因子(如 TNF-α 和 IL-1β)的释放有关、52 据报道,钛纳米粒子可启动依赖于 TLR4(类收费受体 4)的通路,并随后导致 MUC5B(粘蛋白 5B)的过量产生,而 MUC5B 参与了人体气道的炎症反应。尽管大量证据表明,种植体(纳米)颗粒的生物效应是炎症性的,但还需要进行更具体的毒理学研究,并在种植体评估过程中纳入生物标志物检测。一些研究报告称,钛牙科植入物会引起过敏反应,如红斑、湿疹、坏死和骨质流失。其中一个例子是氧化锆和聚芳醚酮 (PEEK),主要由于其良好的生物相容性和生物力学特性,这种材料在牙科应用中越来越受到关注。本评论只关注以钛为基础的金属植入物,作者承认使用替代材料制造的植入物也存在颗粒释放和累积的倾向。然而,现在必须关注与钛种植体相关的潜在不良影响,尤其是其磨损颗粒。需要制定一套新的标准来评估生物对种植体磨损颗粒和金属离子的反应,目的是提高材料和牙科种植体临床前评估的预测能力。这些测试数据应随时可用,以便临床医生和患者了解牙科种植体所用材料的生物和机械影响。牙科植入物的提供者,无论是生产商还是植入物的临床医生,都需要意识到这些潜在的风险以及制定更多测试标准的必要性,因为他们不可避免地要对所使用的产品和向公众提供的治疗承担责任。SL参与了文章的起草和重要修改。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.00
自引率
13.90%
发文量
103
审稿时长
4-8 weeks
期刊介绍: The goal of Clinical Implant Dentistry and Related Research is to advance the scientific and technical aspects relating to dental implants and related scientific subjects. Dissemination of new and evolving information related to dental implants and the related science is the primary goal of our journal. The range of topics covered by the journals will include but be not limited to: New scientific developments relating to bone Implant surfaces and their relationship to the surrounding tissues Computer aided implant designs Computer aided prosthetic designs Immediate implant loading Immediate implant placement Materials relating to bone induction and conduction New surgical methods relating to implant placement New materials and methods relating to implant restorations Methods for determining implant stability A primary focus of the journal is publication of evidenced based articles evaluating to new dental implants, techniques and multicenter studies evaluating these treatments. In addition basic science research relating to wound healing and osseointegration will be an important focus for the journal.
期刊最新文献
Issue Information Featured Cover A transcrestal sinus floor elevation strategy based on a haptic robot system: An in vitro study Influence of repeated implant‐abutment manipulation on the prevalence of peri‐implant diseases in complete arch restorations. A retrospective analysis Biocompatibility and dimensional stability through the use of 3D‐printed scaffolds made by polycaprolactone and bioglass‐7: An in vitro and in vivo study
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