Cold Plasma Treatment on Titanium Implants and Osseointegration: A Systematic Review

Background/Objectives: Osseointegration of titanium dental implants is essential for the long-term success of prosthetic treatments. Cold atmospheric pressure plasma (CAP) has recently emerged as a promising surface modification technique aimed at enhancing early osseointegration by improving implant surface properties and exerting antimicrobial effects. This systematic review aims to critically evaluate the in vivo preclinical evidence on the effects of CAP or similar cold plasma treatments on titanium dental implant surfaces with regard to osseointegration outcomes. Methods: A systematic literature search was conducted in PubMed and Scopus databases for preclinical in vivo studies published between 2005 and 2025 investigating the effects of cold plasma on titanium dental implant surfaces. The primary outcome assessed was the bone-to-implant contact (BIC), followed by secondary outcomes including implant stability quotient (ISQ), removal torque, bone area fraction occupancy (BAFO), peri-implant bone density (PIBD), interfacial bone density (IBD), bone-implant direct weight (BDWT) and bone loss measurements via histology and micro-CT. Risk of bias was evaluated using the SYRCLE Risk of Bias tool. Results: Nine eligible studies involving 310 titanium implants in 71 animal models (dogs, pigs and mice) were included. CAP-treated implants consistently demonstrated significant improvements in early osseointegration parameters compared to controls, with statistically significant increases in BIC (up to +20%), BAFO and biomechanical fixation metrics (removal torque and ISQ). Micro-CT analyses revealed enhanced peri-implant bone density and architecture. No adverse biological events or implant failures related to plasma treatment were reported. However, heterogeneity in plasma protocols, animal species and short follow-up durations (2–12 weeks) limited comparability and long-term interpretation. Conclusions: Preclinical evidence seems to support CAP as a safe and potentially effective surface treatment for enhancing early osseointegration of titanium dental implants. Further standardized long-term studies involving functional loading and clinical trials in humans are needed to confirm clinical efficacy and optimize treatment protocols.