Dental implants are a prevalent solution for tooth replacement, with titanium being the most common material due to its biocompatibility and mechanical properties. However, titanium's biocompatibility extends to bacteria, making peri-implant infections a significant concern. Peri-implant infections can occur at any stage, but are most critical in the initial four weeks post-implantation before osseointegration is complete. Existing antibacterial coatings often suffer from rapid efficacy decline, failing to provide sufficient long-term protection. Peri-implantitis, a later-stage infection, is also challenging to treat due to biofilm formation and the potential for antibiotic resistance. The development of a long-lasting, renewable antibacterial coating is crucial to address these issues and improve the success rate of dental implants. This research focuses on developing such a coating to prevent early infections and effectively treat peri-implantitis.

Numerous strategies have been explored to reduce bacterial adhesion and biofilm formation on titanium implants, including surface modifications with various antibacterial agents. These include metal ions, antibiotics, antimicrobial peptides, polymeric quaternary ammonium salts, and N-halamines. However, many of these approaches suffer from limitations such as rapid loss of antibacterial activity, toxicity concerns, or the development of bacterial resistance. N-halamines, while possessing strong and broad-spectrum antibacterial properties, have limited applications in dental implants despite their potential for long-term stability and renewability.

The researchers developed a porous N-halamine polymeric coating on titanium surfaces through a three-step process: 1) surface pore-making via alkali-heat treatment to increase surface area; 2) surface grafting of polyacrylic acid (PAA); and 3) N-Cl functionalization using ethanediamine and sodium hypochlorite (NaOCl). The resulting Ti-PAA-NCI coating was characterized using various techniques including FTIR, SEM, CLSM, elemental mapping, contact angle measurement, and atomic force microscopy (AFM). The thermal and storage stability of the coating were evaluated through TGA and Cl+ content measurements. Antibacterial activity was assessed against *Staphylococcus aureus* and *Porphyromonas gingivalis*, both key pathogens in peri-implant infections, using release and contact killing assays, SEM imaging, and live/dead staining. Long-lasting antibacterial effects were assessed over extended periods *in vitro* and through repeated cycles. The renewable antibacterial properties were evaluated by depleting the active chlorine (Cl+) with sodium thiosulfate and then regenerating it with NaOCl. The coating's effectiveness against complex bacteria from peri-implantitis patients was evaluated under both aerobic and anaerobic conditions using biofilm biomass quantification and live/dead staining. Biocompatibility was assessed using CCK-8 assay, cell morphology analysis, ALP activity, Alizarin Red S staining, and RT-qPCR and western blot analyses of osteogenic genes and proteins in MC3T3-E1 preosteoblasts. *In vivo* biocompatibility and osseointegration were assessed using a nude mouse model and a rabbit model of ligature-induced peri-implantitis, with micro-CT analysis and biomechanical testing. Finally, the long-lasting and renewable antibacterial properties *in vivo* were assessed using human volunteers, with titanium disks bonded to their teeth and subsequently analyzed after 4 and 12 weeks.

The porous N-halamine polymeric coating (Ti-PAA-NCI) exhibited high antibacterial activity against both *S. aureus* and *P. gingivalis*, achieving average antibacterial rates of 64% and 42% respectively through release killing, and 96% and 91% respectively through contact killing. The coating demonstrated long-lasting antibacterial properties, maintaining 79% efficacy against *P. gingivalis* even after 12 weeks *in vitro*. The renewable nature of the coating was confirmed, with Cl+ content nearly restored to original levels after rechlorination. The Ti-PAA-NCI coating showed efficacy against complex bacteria from peri-implantitis patients, reducing biofilm biomass by 56% (anaerobic) and 62% (aerobic). Biocompatibility studies revealed no significant cytotoxicity or adverse effects on osteogenic differentiation and function. *In vivo* studies in nude mice confirmed good biocompatibility. The rabbit model of peri-implantitis demonstrated that Ti-PAA-NCI significantly enhanced bone regeneration and improved the implant-bone bonding force compared to the control group. Human intraoral studies showed that after 4 weeks, bacterial coverage and fluorescence intensity on Ti-PAA-NCI were 18% and 7% of that on Ti-OH, respectively, and after rechlorination, these values reduced further to 3% and 2%, respectively. Even after 12 weeks, Ti-PAA-NCI displayed significant antibacterial activity, with rechlorination further enhancing its effect.

The successful development of the porous Ti-PAA-NCI coating addresses the limitations of existing antibacterial coatings for dental implants. The combination of amide and amine N-halamine structures likely contributes to both rapid (release killing) and long-lasting (contact killing) antibacterial effects. The mechanism involves active chlorine's interaction with bacterial proteins, leading to cell death without promoting antibiotic resistance. The renewability of the coating through simple rechlorination offers a unique advantage for treating peri-implantitis. The results from *in vitro*, animal, and human studies strongly support the potential of this coating to significantly improve dental implant success rates by preventing early infections and facilitating the treatment of peri-implantitis.

This study successfully created a porous N-halamine polymeric coating for titanium implants with long-lasting, renewable antibacterial properties. This innovative coating shows promise for significantly enhancing dental implant success by preventing peri-implant infections and effectively treating peri-implantitis. Future research could explore optimizing the coating's properties, investigating its efficacy against a wider range of bacteria, and conducting larger-scale clinical trials.

The study's *in vivo* experiments used relatively small sample sizes, particularly in the human intraoral study. While the renewable nature of the coating was demonstrated, the long-term effects of repeated rechlorination on the coating's properties and biocompatibility need further investigation. The specific mechanisms underlying the coating's effects on bone regeneration require further elucidation.