Mapping the osseointegration using immuno-driven biological processes: evidences from a systematic review and a randomized clinical trial with focus on occlusal loading of implant-retained mandibular overdentures wearers

The dental implant osseointegration occurs due to the process triggered by the host immune response, however the biomarkers that modulate this process have not yet been determined. In order to investigate and understand ossointegration through the biomarkers, two studies were designed: I) Systematic Review (SR) focusing on the evaluation of peri-implant crevicular fluid collection (FCPI) during bone healing after dental implants insertion; II) Longitudinal Randomized Clinical Trial according to the occlusal loading, immediate (IML) or conventional (CL), of implant retained mandibular overdentures. The study II evaluated the clinical and biological behavior of narrow diameter implants (NDR) osseointegration submitted to IML or CC, inserted in 20 totally edentulous patients, with a high edentulism time and limited mandibular bone availability. The SR selected 30 clinical studies and identify 52 biomarkers reported during osseointegration. The most studied biomarkers were interleukin (IL) -1β, tumor necrosis factor alpha (TNF-α) and nitric oxide (NO). PICF collections were performed immediately after implant insertion up to 16 weeks, prior to occlusal loading. Through the data collected, it was not possible to identify the mechanism by which inflammatory and bone biomarkers are released during osseointegration. However, it was possible to associate cellular and molecular events triggered with osseointegration with the results of available clinical studies. The data summarized can guide researchres to design future clinical studies and can help selecting target biomarkers already quantified. The study "II” showed that IML group presented implant stability 8.95% lower than the CL, until week 12 (p <0.05). The calculus presence in IML group was 50% higher than the CL at week 1 (p = 0.006), and 30% lower at week 8 (p = 0.017). The IML probing in depth was about 21.49% lower than in the CL group for all evaluated periods (p = 0.05). The bleeding on probing was 28.9% higher for IML at week 12 (p = 0.044). IML group presented the highest TNF-α concentration by week 4 (p <0.05) and 57.78% more IL-1β after week 4 to 12 than the CL group. The IL-6 concentration was 53.94% lower for IML group until week 8. The IL-10 concentration had a significant progressive and similar increase for both groups until week 8, and at week 12 the IML group had 45.74% higher concentration than the CL group (p = 0.003). The implant survival rate was 90% for IML and CL. The implants immediately loaded showed more stable clinical results, however presented unstable biological resposnes during bone healing. Therefore, the rehabilitation of the population with low bone availability in the anterior region of the mandible using implant retained mandibular overdentures seems to be safer when CL is adopted based on the inflammatory biomarker release.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA osseointegração de implantes dentários ocorre devido ao processo desencadeado pela resposta imune do hospedeiro, entretanto os biomarcadores que modulam esse processo ainda não foram determinados. Com o intuito de investigar e compreender a ossointegração por meio dos biomarcadores foram delineados dois estudos: I) Revisão sistemática (RS) com foco na avaliação de coleta de fluido crevicular peri-implantar (FCPI) durante a cicatrização de óssea após a inserção de implantes dentários; II) Estudo clínico longitudinal randomizado de acordo com o carregamento oclusal, carga imediata (CI) ou convencional (CC), de overdentures mandibulares. O estudo II avaliou o comportamento clínico e biológico da osseointegração de implantes de diâmetro reduzido (IDR) submetidos a CI ou CC, inseridos em 20 pacientes desdentados totais, com elevado tempo de edentulismo e limitada disponibilidade óssea mandibular. Na RS foram selecionados 30 estudos clínicos e identificados 52 biomarcadores durante o período de osseointegração. Os biomarcadores mais estudados foram interleucina (IL) -1β, fator de necrose tumoral alfa (TNF-α) e óxido nítrico (NO). As coletas de FCPI foram realizadas imediatamente após inserção do implante até 16 semanas antes do carregamento oclusal. Através dos dados coletados nesta RS, não foi possível identificar qual o mecanismo pelos quais os biomarcadores inflamatórios e ósseos são liberados durante a osseointegração. No entanto, eventos já conhecidos da osseointegração foram associados com os resultados dos estudos clínicos disponíveis, sendo este, um guia aos futuros pesquisadores, devido o mapeamento de todos os biomarcadores já avaliados durante esse processo. No estudo “II”, o grupo CI apresentou estabilidade 8,95% menor que o CC, até a semana 12 (p<0,05). O cálculo no CI foi 50% maior que no CC na semana 1 (p=0.006), e 30% menor na semana 8 (p=0.017). A profundidade a sondagem do CI foi em média 21,49% inferior ao grupo CC em todos os períodos avaliados (p=0.05). O sangramento a sondagem foi 28,9% maior para o CI na semana 12 (p=0,044). Implantes que receberam CI apresentaram a concentração de TNF-α 40,75% maior até a semana 4 (p