Bone Tissue Interaction with Ti Implant |
After dental implants are anchored, a sequence of immune-inflammatory responses, followed by angiogenesis and osteogenesis, occur to achieve osseointegration. These events play a key role in the initial homeostasis as they release cytokines and growth factors that stimulate deposition of the collagenous matrix around the titanium oxide layer, leading to newly formed bone tissue (usually occurs 5 days later). Osteoclasts drive the process of bone resorption and remodeling and replacement by lamellar bone with a higher degree of mineralization. Titanium induces bioactivity favoring bone remodeling over resorption. The osteoblasts attach themselves to the mineralized collagenous matrix, forming a sealing zone, depositing bone directly on the implant surface (micro scale). In 8 to 12 weeks, the lamellar bone begins biological stability, meaning osseointegration. |
Lee & Bance [1212 Lee JWY, Bance ML. Physiology of Osseointegration. Otolaryngol Clin North Am. 2019;52(2):231-242. http://dx.doi.org/10.1016/j.otc.2018.11.004. https://doi.org/10.1016/j.otc.2018.11.00...
] Insua et al. [1313 Insua A, Monje A, Wang HL, Miron RJ. Basis of bone metabolism around dental implants during osseointegration and peri-implant bone loss. J Biomed Mater Res A. 2017;105(7):2075-2089. http://dx.doi.org/10.1002/jbm.a.36060 https://doi.org/10.1002/jbm.a.36060...
] Terheyden et al. [1414 Terheyden H, Lang NP, Bierbaum S, Stadlinger B. Osseointegration: communication of cells. Clin Oral Implants Res. 2011;23(10):1127-1135. http://dx.doi.org/10.1111/j.1600-0501.2011.02327.x https://doi.org/10.1111/j.1600-0501.2011...
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Surface Topography |
The topography of the dental implant can be classified into macro-, micro- and nanoscale. It is crucial for adhesion and differentiation of osteoblasts during the initial phase of osseointegration, as well as in long-term bone remodeling. It can be modified at various levels, from the macroscopic design or shape of the implant to the introduction of microscopic, or nanoscopic topographies superimposed on each other, in order to alter growth, metabolism and migration, as well as cytokine and osteogenic cell growth factor production. |
Smeets et al. [22 Smeets R, Stadlinger B, Schwarz F, Beck-Broichsitter B, Jung O, et al. Impact of dental implant surface modifications on osseointegration. Biomed Res Int. 2016;2016:6285620. https://doi.org//10.1155/2016/6285619 https://doi.org/10.1155/2016/6285619...
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Roughness |
Surface roughness is a parameter that affects the osteoconduction rate, mainly influencing the establishment of primary stability. Rougher surfaces are directly proportional with a higher microbial colonization while smoother surfaces tend to aggregate a lower colonization. In addition, immune system cells such as neutrophils, monocytes, dendritic cells, and macrophages are affected and modulate their response depending on the surface roughness. |
Elias et al. [1515 Elias CN, Oshida Y, Lima JH, Muller CA. Relationship between surface properties (roughness, wettability and morphology) of titanium and dental implant removal torque. J Mech Behav Biomed Mater. 2008;1(3):234-42. http://dx.doi.org/10.1016/j.jmbbm.2007.12.002. Epub 2007 Dec 31. https://doi.org/10.1016/j.jmbbm.2007.12....
] Rohr et al. [1616 Rohr N, Bergemann C, Nebe JB, Fischer J. Crystal structure of zirconia affects osteoblast behavior. Dent Mater. 2020;36(7):905-913. http://dx.doi.org/10.1016/j.dental.2020.04.017 https://doi.org/10.1016/j.dental.2020.04...
] Leite et al. [1717 Leite GB, Fonseca YR, Gomes AV, Elias CN. Relação entre os parâmetros de rugosidade 3D e a molhabilidade do titânio com grãos micrométricos e sub-micrométricos. Matéria (Rio J.). 2020;25(2):e-12655. http://dx.doi.org/10.1590/s1517-707620200002.1055 https://doi.org/10.1590/s1517-7076202000...
] Brito et al. [1818 Brito TO, Nascimento M, Rocha AML, Nattrodt AKR, Marques AA, Netto MCB, Lima MPS, Souza BMS, Morales LMM, Elias CN. A influência da rugosidade nos mecanismos da osseointegração de implantes: uma revisão de literatura. In: CB Fadel, organizadora. Odontologia: Pesquisa e Práticas Contemporâneas. Brasil: Editora Científica; 2021. v.2, p.44-58 http://dx.doi.org/10.37885/211106833 https://doi.org/10.37885/211106833...
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Wettability |
Wettability is expressed by the water contact angle that ranges from 0° to 90° on hydrophilic surfaces to greater than 90° on hydrophobic surfaces. Perhaps the most influential surface property in modulating the activation of anti-inflammatory macrophages is surface energy (usually calculated, indirectly, by means of wettability). Increasing surface energy greatly elevates the anti-inflammatory macrophage polarization in various applications. Hydrophilic surfaces significantly decrease pro-inflammatory leukocyte activation compared to hydrophobic, cationic, or anionic surfaces. |
Zhou et al. [44 Zhou P, Long S, Mao F, Huang H, Li H, et al. Controlling cell viability and bacterial attachment through fabricating extracellular matrix-like micro/nanostructured surface on titanium implant. Biomed Mater. 2020;15(3):035002. http://dx.doi.org/10.1088/1748-605X/ab70ee https://doi.org/10.1088/1748-605X/ab70ee...
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Primary Stability |
Primary implant stability is an indirect indication of osseointegration and can be assessed, clinically, by: clinical mobility testing, radiological imaging, resonance frequency analysis. With implant insertion, a dental implant gains primary stability. The implant is passively stabilized in the surgical wound by mechanical friction with the primary bone contacts. The denser the host bone, the more primary bone contacts are available and the greater the primary stability. Primary stability implies that the friction holding the implant in place is greater than the higher dynamic loading forces applied. |
Khan et al. [55 Khan SN, Ramachandran M, Senthil SK, Krishnan V, Sundaram R. Osseointegration and more: a review of literature. Indian J Dentistry. 2012;3(2):72-76. http://dx.doi.org/10.1016/j.ijd.2012.03.011 https://doi.org/10.1016/j.ijd.2012.03.01...
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Microbiota-Inmune System-Host Interaction |
The microorganisms indigenous to the oral microbiome live in a symbiotic state with the host, adhering to any biotic or abiotic surfaces present in this ecosystem. Microbial accumulation and biofilm formation on implanted materials can trigger various biological and chemical processes, such as polymicrobial infections and biomaterial deterioration. The Ti particles released by microbial corrosion, increase the release of pro-inflammatory cytokines, infiltration of immune-inflammatory cells and activation of osteoclastic activity, generating unfavorable results. Therefore, the presence of Ti products around dental implants may contribute to peri-implant bone resorption, microbial dysbiosis, and consequently increase the risk of developing peri-implantitis of osseointegration failure. The different conditions that the subgingival microbiota may find itself in, whether in symbiosis or dysbiosis, together with the surface characteristics of Ti implants, will influence the polarization of different immune cell profiles, generating immune cascades with different cellular responses, ultimately causing a positive or negative modulation of the osseointegration process. |
Costa et al. [33 Costa RC, Abdo VL, Mendes PHC, Mota-Veloso I, Bertolini M, et al. Correction to: microbial corrosion in titanium based dental implants: how tiny bacteria can create a big problem? J Bio Tribo Corros. 2021;7:136. https://doi.org/10.1007/s40735-021-00575-8 https://doi.org/10.1007/s40735-021-00575...
] Albrektsson et al. [99 Albrektsson T, Jemt T, Mölne J, Tengvall P, Wennerberg A. On inflammation-immunological balance theory-A critical apprehension of disease concepts around implants: Mucositis and marginal bone loss may represent normal conditions and not necessarily a state of disease. Clin Implant Dent Relat Res. 2019;21(1):183-189. http://dx.doi.org/10.1111/cid.12711. Epub 2018 Dec 28. https://doi.org/10.1111/cid.12711...
] Belibasakis & Manoil [1919 Belibasakis GN, Manoil D. Microbial community-driven etiopathogenesis of peri-implantitis. J Dent Res. 2021;100(1):21-28. http://dx.doi.org/10.1177/0022034520949851. Epub 2020 Aug 12. https://doi.org/10.1177/0022034520949851...
] Albrektsson et al. [2020 Albrektsson T, Dahlin C, Reinedahl D, Tengvall P, Trindade R, Wennerberg A. An imbalance of the immune system instead of a disease behind marginal bone loss around oral implants: position paper. Int J Oral Maxillofac Implants. 2020;35(3):495-502. http://dx.doi.org/10.11607/jomi.8218 https://doi.org/10.11607/jomi.8218...
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Peri-implantitis |
It is a polymicrobial infection around dental implants in prosthetic function, causing inflammation of the peri-implant tissue (release of inflammatory mediators of periodontal disease), which may lead to progressive damage to the supporting bone tissue and occasionally to implant loss. In other words, biofilm formation on the surfaces of dental implants is one of the main causes of the etiopathogenesis of peri-implantitis, and the main reason for implant failure. The resulting changes in the implant microenvironment cause dysbiotic changes that exacerbate inflammatory progression, and it has been shown that the peri-implant microbiota gradually gains complexity as the infection progresses. |
Charalampakis & Belibasakis [11 Charalampakis G, Belibasakis GN. Microbiome of peri-implant infections: lessons from conventional, molecular and metagenomic analyses. Virulence. 2015;6(3):183-187. http://dx.doi.org/10.4161/21505594.2014.980661. https://doi.org/10.4161/21505594.2014.98...
] Faveri et al. [77 Faveri M, Figueiredo LC, Shibli JA, Pérez-Chaparro PJ, Feres M. Microbiological diversity of peri-implantitis biofilms. Adv Exp Med Biol. 2015;830:85-96. http://dx.doi.org/10.1007/978-3-319-11038-7_5 https://doi.org/10.1007/978-3-319-11038-...
] Zheng et al. [88 Zheng H, Xu L, Wang Z, Li L, Zhang J, et al. Subgingival microbiome in patients with healthy and ailing dental implants. Sci Rep. 2015;5:10948. http://dx.doi.org/10.1038/srep10948 https://doi.org/10.1038/srep10948...
] Pérez-Chaparro et al. [2121 Pérez-Chaparro PJ, Duarte PM, Shibli JA, Montenegro S, Lacerda SH, et al. The current weight of evidence of the microbiologic profile associated with peri-implantitis: a systematic review. J Periodontol. 2016;87(11):1295-1304. http://dx.doi.org/10.1902/jop.2016.160184 https://doi.org/10.1902/jop.2016.160184...
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Peri-implantitis |
It is a polymicrobial infection around dental implants in prosthetic function, causing inflammation of the peri-implant tissue (release of inflammatory mediators of periodontal disease), which may lead to progressive damage to the supporting bone tissue and occasionally to implant loss. In other words, biofilm formation on the surfaces of dental implants is one of the main causes of the etiopathogenesis of peri-implantitis, and the main reason for implant failure. The resulting changes in the implant microenvironment cause dysbiotic changes that exacerbate inflammatory progression, and it has been shown that the peri-implant microbiota gradually gains complexity as the infection progresses. |
Charalampakis & Belibasakis [11 Charalampakis G, Belibasakis GN. Microbiome of peri-implant infections: lessons from conventional, molecular and metagenomic analyses. Virulence. 2015;6(3):183-187. http://dx.doi.org/10.4161/21505594.2014.980661. https://doi.org/10.4161/21505594.2014.98...
] Faveri et al. [77 Faveri M, Figueiredo LC, Shibli JA, Pérez-Chaparro PJ, Feres M. Microbiological diversity of peri-implantitis biofilms. Adv Exp Med Biol. 2015;830:85-96. http://dx.doi.org/10.1007/978-3-319-11038-7_5 https://doi.org/10.1007/978-3-319-11038-...
] Zheng et al. [88 Zheng H, Xu L, Wang Z, Li L, Zhang J, et al. Subgingival microbiome in patients with healthy and ailing dental implants. Sci Rep. 2015;5:10948. http://dx.doi.org/10.1038/srep10948 https://doi.org/10.1038/srep10948...
] Pérez-Chaparro et al. [2121 Pérez-Chaparro PJ, Duarte PM, Shibli JA, Montenegro S, Lacerda SH, et al. The current weight of evidence of the microbiologic profile associated with peri-implantitis: a systematic review. J Periodontol. 2016;87(11):1295-1304. http://dx.doi.org/10.1902/jop.2016.160184 https://doi.org/10.1902/jop.2016.160184...
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Innate Immune Response |
It is the first response to harmful stimuli. It counts on the action of neutrophils, monocytes, and macrophages. Neutrophils and macrophages have phagocytic and signaling functions, especially at the beginning of the inflammatory phase of biomaterial implantation. Ultimately, these cell types determine the outcome of implants as inflammation, foreign body response, fibrointegration or osseointegration. Neutrophils exhibit distinct phenotypes along a pro-anti-inflammatory spectrum, although these phenotypes are not as well characterized as those of macrophages. M1 macrophages are considered harmful to tissue repair. In contrast, M2 macrophages have pro-regenerative capabilities. |
Zhang et al. [1010 Zhang B, Su Y, Zhou J, Zheng Y, Zhu D. Toward a Better Regeneration through Implant-Mediated Immunomodulation: Harnessing the Immune Responses. Adv Sci (Weinh). 2021;8(16):e2100446. http://dx.doi.org/10.1002/advs.202100446 https://doi.org/10.1002/advs.202100446...
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Adaptive Immune Response |
When innate immune cells fail to defeat the threat of invasion, mobilization of adaptive immunity occurs from B and T cells, which can specifically eliminate the threat encountered. There are several subsets of T cells with distinct functionalities triggered by different chemokines and cytokines. Dendritic cells play roles similar to macrophages, promoting early inflammation and resolving late inflammation. B cells have as their main role during the immune response to present antigens and produce antibodies. |
Abaricia et al. [1111 Abaricia JO, Farzad N, Heath TJ, Simmons J, Morandini L, Olivares-Navarrete R. Control of innate immune response by biomaterial surface topography, energy, and stiffness. Acta Biomater. 2021;133:58-73. http://dx.doi.org/10.1016/j.actbio.2021.04.021 https://doi.org/10.1016/j.actbio.2021.04...
] |
Innate Immune Response |
It is the first response to harmful stimuli. It counts on the action of neutrophils, monocytes, and macrophages. Neutrophils and macrophages have phagocytic and signaling functions, especially at the beginning of the inflammatory phase of biomaterial implantation. Ultimately, these cell types determine the outcome of implants as inflammation, foreign body response, fibrointegration or osseointegration. Neutrophils exhibit distinct phenotypes along a pro-anti-inflammatory spectrum, although these phenotypes are not as well characterized as those of macrophages. M1 macrophages are considered harmful to tissue repair. In contrast, M2 macrophages have pro-regenerative capabilities. |
Zhang et al. [1010 Zhang B, Su Y, Zhou J, Zheng Y, Zhu D. Toward a Better Regeneration through Implant-Mediated Immunomodulation: Harnessing the Immune Responses. Adv Sci (Weinh). 2021;8(16):e2100446. http://dx.doi.org/10.1002/advs.202100446 https://doi.org/10.1002/advs.202100446...
] |
Adaptive Immune Response |
When innate immune cells fail to defeat the threat of invasion, mobilization of adaptive immunity occurs from B and T cells, which can specifically eliminate the threat encountered. There are several subsets of T cells with distinct functionalities triggered by different chemokines and cytokines. Dendritic cells play roles similar to macrophages, promoting early inflammation and resolving late inflammation. B cells have as their main role during the immune response to present antigens and produce antibodies. |
Abaricia et al. [1111 Abaricia JO, Farzad N, Heath TJ, Simmons J, Morandini L, Olivares-Navarrete R. Control of innate immune response by biomaterial surface topography, energy, and stiffness. Acta Biomater. 2021;133:58-73. http://dx.doi.org/10.1016/j.actbio.2021.04.021 https://doi.org/10.1016/j.actbio.2021.04...
] |