Abstract / Summary
The long-term success of dental implants depends on rapid and stable osseointegration. Numerous surface treatments and biologic adjuncts have been proposed to enhance early bone anchorage, but the strength and consistency of the available preclinical and clinical evidence remain uncertain. To synthesise evidence from preclinical animal models and human clinical studies evaluating the influence of titanium implant surface modifications, biologic adjuncts, and systemic factors on osseointegration-related outcomes. A protocol was established following the PRISMA 2020 guidelines and subsequently registered with PROSPERO (CRD420251153021). A comprehensive search was conducted across PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar from their inception through December 2025. The studies included in this review comprised both in vivo animal research and human clinical trials that examined modified titanium implant surfaces, supplementary biological therapies or systemic modifiers, and provided quantitative outcomes related to osseointegration. The primary outcomes measured were bone-to-implant contact percentage (BIC%), implant stability quotient (ISQ), changes in marginal bone levels, radiographic bone density, and bone volume fraction. The risk of bias was evaluated using the SYRCLE tool, Cochrane RoB 2.0, and the JBI checklist where applicable. Animal and human evidence were synthesized qualitatively, whereas random-effects meta-analysis was performed only for clinically comparable human studies reporting common outcomes. Fourteen studies met the inclusion criteria (eight animal and six human). Roughened, hydrophilic, nanostructured, UV- or plasma-activated surfaces, as well as platelet-derived concentrates and concentrated growth factors, generally demonstrated favourable effects on osseointegration-related outcomes, including higher BIC, bone volume, and earlier implant stability, whereas diabetes and pharmacologic VEGF blockade were associated with impaired osseointegration. Pooled analysis of four human trials showed higher ISQ values for test interventions (SMD 1.37; 95% CI 1.02-1.73; P < 0.00001; I2 = 5%). Two human trials reporting radiographic bone density also favoured the experimental protocols (SMD -1.26; 95% CI -1.74 to -0.78; P < 0.00001; I2 = 4%). However, interpretation of the radiographic bone density analysis is limited because only two studies contributed quantitative data. Human studies generally demonstrated low-to-moderate risk of bias, whereas several animal studies showed unclear randomisation and blinding. The certainty of evidence ranged from low to moderate across the primary outcomes. The available evidence suggests that surface-optimised and biologically augmented titanium implants may improve early osseointegration and implant stability, whereas adverse systemic conditions may compromise these benefits The quality of evidence is not very good because of methodological limitations, clinical heterogeneity, and the limited number of studies available for quantitative synthesis. More robust and mechanistic clinical trials with standardised reporting are needed to improve surface selection and biologic strategies for different patient profiles.