Periodontal disease, a global health burden linked to dysbiotic oral polymicrobial communities and disrupted immune-inflammatory responses, is critically mediated byPorphyromonas gingivalis(Pg)─the keystone pathogen that sabotages host immunity, triggers tissue inflammation and destruction, and disrupts microbiota balance. Effective therapies should combine antimicrobial action, immune modulation, virulence suppression, and microbiome restoration. Bismuth ions and berberine, which exhibit antimicrobial and epithelial barrier-protecting effects, show potential effectiveness in treating periodontal diseases but face practical limitations due to poor water solubility and bioavailability. To address this, we developed bismuth-doped carbon dots functionalized with structure-modified berberine (BiCD-Ber) as a multifunctional nanomedicine. BiCD-Ber eradicated Pg in various forms, restored Pg-perturbed immune responses in gingival fibroblasts, and preserved epithelial barrier integrity. The doped bismuth ions neutralized Pg virulence factors by blocking the catalytic sites of gingipains. To facilitate in vivo delivery, BiCD-Ber was encapsulated in a disulfide-modified hyaluronic acid hydrogel that degrades in response to Pg metabolites. This BiCD-Ber hydrogel system modulated subgingival microbiota, alleviated inflammation in gingiva, and thereby prevented alveolar bone loss. This approach to concurrently eliminating Pg, modulating inflammatory responses , suppressing virulence factors, and restoring microbiota showcases great potential in managing periodontitis effectively.

Background and Purpose: Micro-/nano-tubes (TNTs) and micro-/nano-nets (TNNs) are the common and sensible choice in the first step of combined modifications of titanium surface for further functionalization in the purpose of extended indications and therapeutic effect. It is important to recognize the respective biologic reactions of these two substrates for guiding a biologically based first-step selection. Materials and Methods: TNTs were produced by anodic oxidation and TNNs were formed by alkali-heat treatment. The original selective laser melting (SLM) titanium surface was set as control. Surface characterization was evaluated by scanning electron microscopy, surface roughness, and water contact angle measurements. Osteoclastogenesis and osteogenesis were measured. MC3T3-E1 cells and RAW 264.7 cells were used for in vitro assay in terms of adhesion, proliferation, and differentiation. In vivo assessments were taken on Beagle dogs with micro-CT and histological analysis. Results: TNN and TNT groups performed decreased roughness and increased hydrophilicity compared with SLM group. For biological detections, the highest ALP activity and osteogenesis-related genes expression were observed in TNT group followed by TNN group (P < 0.05). Interestingly, when it comes to the osteoclastogenesis, TNNs displayed lowest TRAP activity and osteoclastogenesis-related genes expression and TNTs were lower than SLM but higher than TNNs (P < 0.05). BV/TV around implants was highest in TNT group after 4 weeks (P < 0.05). HE, ALP and TRAP staining showed that osteogenic and osteoclastic activity around TNTs were both higher than TNNs (P < 0.05). Conclusion: TNNs and TNTs have dual advantages in promotion of osteogenesis and inhibition of osteoclastogenesis. Furthermore, TNNs showed better capability in inhibiting osteoclast activity while TNTs facilitated stronger osteogenesis. Our results implied that TNT substrates would take advantage in early application after implantation, while diseases with inappropriate osteoclast activity would prefer TNN substrates, which will guide a biologically based first-step selection on combined modification for different clinical purposes.

Selective laser melting (SLM) titanium is a suitable material for use in customized implants. However, long-term implant survival requires both successful osseointegration and promising antibacterial characteristics. Native SLM titanium thus requires proper modifications to improve its bioactivity and antibacterial efficacy. Micro-arc oxidation (MAO) was conducted on sandblasted SLM substrate to form a microporous TiO₂ coating. Subsequently, hydrothermal treatment was applied to fabricate micro-nano zinc-incorporated coatings with different Zn content (1 mM-Zn and 100 μM-Zn). Surface characterization was performed using scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, a three-dimensional profilometer, and a contact angle measuring device. The osteoblast-like cell line MC3T3-E1, Subclone 14, was used in cell viability assays to evaluate adhesion, proliferation, and ALP activity. An antibacterial assay was conducted using Streptococcus sanguinis and Fusobacterium nucleatum. Zn-incorporated samples exhibited higher adhesion, proliferation, and differentiation than did SLM and MAO samples. 100 μM Zn samples exhibited the highest proliferation, and 1 mM-Zn samples manifested the highest ALP activity. In addition, Zn-incorporated samples exerted inhibitory effects on both Streptococcus sanguinis and Fusobacterium nucleatum. Combining micro-arc oxidation and hydrothermal treatment, we successfully fabricated a novel Zn-incorporated coating on a microporous SLM surface which possesses both outstanding bioactivity and antibacterial efficacy.

Selective laser melting used in manufacturing custom-made titanium implants becomes more popular. In view of the important role played by osteoclasts in peri-implant bone resorption and osseointegration, we modified selective laser melting-manufactured titanium surfaces using sandblasting/alkali-heating and sandblasting/acid-etching, and investigated their effect on osteoclast differentiation as well as their underlying mechanisms. The properties of the surfaces, including elements, roughness, wettability and topography, were analyzed. We evaluated the proliferation and morphology of primary mouse bone marrow-derived monocytes, as well as induced osteoclasts derived from bone marrow-derived monocytes, on samples. Then, osteoclast differentiation was determined by the tartrate-resistant acid phosphatase activity assay, calcitonin receptors immunofluorescence staining and the expression of osteoclast-related genes. The results showed that sandblasting/alkali-heating established nanonet structure with the lowest water contact angle, and both sandblasting/alkali-heating and sandblasting/acid-etching significantly decreased surface roughness and heterogeneity compared with selective laser melting. Surface modifications of selective laser melting-produced titanium altered bone marrow-derived monocyte morphology and suppressed bone marrow-derived monocyte proliferation and osteoclastogenesis in vitro (sandblasting/alkali-heating>sandblasting/acid-etching>selective laser melting). These surface modifications reduced the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinases compared to native-selective laser melting. Sandblasting/alkali-heating additionally blocked tumor necrosis factor receptor-associated factor 6 recruitment. The results suggested that sandblasting/alkali-heating and sandblasting/acid-etching modifications on selective laser melting titanium could inhibit osteoclast differentiation through suppressing extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylation in mitogen-activated protein kinase signaling pathway and provide a promising technique which might reduce peri-implant bone resorption for optimizing native-selective laser melting implants.