Surface coating modification of titanium-based alloys is an efficient way to accelerate early osseointegration in dental implant fields. Icariin (ICA) is a traditional Chinese medicine that has bone activating functions, while aspirin (ASP) is a classical non-steroidal anti-inflammatory drug with good antipyretic and analgesic capabilities. Moreover, poly(lactic–co–glycolic acid) (PLGA) has attracted great attention due to its excellent biocompatibility and biodegradability. We superimposed an ASP/PLGA coating onto ICA loaded TiO₂ nanotubes structure so as to establish an icariin/aspirin composite coating on TiO₂ nanotubes surface. Scanning electron microscopy, X-ray photoelectron spectroscopy, a contact angle test and a drug release test confirmed the successful preparation of the NT–ICA–ASP/PLGA substrate, with a sustained release pattern of both ICA and ASP. Compared to those cultured on the Ti surface, macrophage cells on the NT-ICA-ASP/PLGA substrate displayed decreased M1 proinflammatory and enhanced M2 proregenerative genes and proteins expression, which implied activated immunomodulatory effect. Moreover, when cultured with conditioned medium from macrophages, osteoblast cells on the NT-ICA-ASP/PLGA substrate revealed improved cell proliferation, adhesion and osteogenic genes and proteins expression, compared with those on the Ti surface. The abovementioned results suggest that the established NT-ICA-ASP/PLGA substrate is a promising candidate for functionalized coating material in Ti implant surface modification.

Surface modification of titanium is encouraged to facilitate early osseointegration in dental and orthopedic fields. Icariin is the main active constituents of Herba Epimedii, which has good bone-promoting ability. We established an icariin-functionalized coating composed of icariin and poly (lactic-co-glycolic acid) (PLGA) on TiO₂ nanotubes surface (NT-ICA-PLGA) to promote osteoblast cell activity and early osseointegration. Surface topography, wettability and drug release pattern of the established NT-ICA-PLGA surface were characterized by scanning electron microscopy (SEM), contact angle test and drug release test. MC3T3-E1 osteoblast cell activity tests were performed using SEM, immunofluorescent staining, cell counting kit-8 and alkaline phosphatase assays. The osteogenic effects of different surfaces were observed using a rat model. Surface characterization proved the successful fabrication of the icariin-functionalized coating on the TiO₂ nanotube structure, with increased wettability. The NT-ICA-PLGA substrate showed sustained release of icariin until two weeks. Osteoblast cells grown on the NT-ICA-PLGA substrate displayed improved cell adhesion, proliferation and differentiation ability than the control Ti surface. The in vivo experiment also revealed superior bone forming ability on the NT-ICA-PLGA surface, compared to the pure Ti control. These results imply that the developed NT-ICA-PLGA substrate has a promising future use as functionalized coating for implant surface modification.

Host immune response has gradually been accepted as a critical factor in achieving successful implant osseointegration. The aim of this study is to create a favorable immune microenvironment by the dominant release of IL-4 during the initial few days after implant insertion to mitigate early inflammatory reactions and facilitate osseointegration. Herein, the B-TNT/PDA/IL-4 substrate was established by immobilizing an interleukin-4 (IL-4)/polydopamine (PDA) coating on a black TiO₂ nanotube (B-TNT) surface, achieving on-demand IL-4 release under near infrared (NIR) irradiation. Gene Ontology (GO) enrichment analyses based on high-throughput DNA microarray data revealed that IL-4 addition inhibited osteoclast differentiation and function. Animal experiment results suggested that the B-TNT/PDA/IL-4+Laser substrate induced the least inflammatory, tartrate-resistant acid phosphatase, inducible nitric oxide synthase and the most CD163 positive cells, compared to the Ti group at 7 days post-implantation. In addition, 28 days post-implantation, micro-computed tomography results showed the highest bone volume/total volume, trabecular thickness, trabecular number and the lowest trabecular separation, while Hematoxylin-eosin and Masson-trichrome staining revealed the largest amount of new bone formation for the B-TNT/PDA/IL-4+Laser group. This study revealed the osteoimmunoregulatory function of the novel B-TNT/PDA/IL-4 surface by photothermal release of IL-4 at an early period post-implantation, thus paving a new way for dental implant surface modification.

Peri-implantitis is driven by persistent multispecies biofilms and a pathological inflammatory microenvironment characterized by elevated reactive oxygen species (ROS), acidic pH, and sustained pro-inflammatory macrophage activation. These coupled features severely limit the efficacy of conventional antimicrobial therapies by restricting drug penetration into mature biofilms and perpetuating immune dysregulation. Therapeutic strategies capable of simultaneously overcoming biofilm mass-transport barriers and restoring immune homeostasis remain lacking. Herein, we report a microenvironment-responsive nanomotor system (M-CaO₂-CL) that converts pathological inflammatory cues into sustained autonomous motion, enabling active biofilm penetration and concurrent immunomodulation. Triggered by elevated hydrogen peroxide (H₂O₂) and sustained by acidic pH, the nanomotors generate continuous oxygen-driven propulsion, facilitating deep infiltration into dense biofilm matrices and overcoming diffusion-limited transport. This motion-enabled behavior markedly enhances antibacterial efficacy, particularly when combined with mild photothermal treatment under near-infrared irradiation (< 48 °C), achieving efficient biofilm disruption without detectable collateral tissue damage. Beyond antibiofilm activity, the nanomotor platform exhibits intrinsic antioxidant and anti-inflammatory functions, effectively scavenging excessive ROS and reprogramming macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype. In a rat peri-implantitis model, M-CaO₂-CL treatment significantly reduced bacterial burden, suppressed pro-inflammatory cytokine expression, and preserved peri-implant bone architecture. Collectively, this study demonstrates a multifunctional nanomotor-based therapeutic strategy that integrates inflammation-responsive propulsion, enhanced biofilm penetration, mild photothermal disinfection, and immune reprogramming. By harnessing pathological microenvironmental cues as endogenous driving forces, the M-CaO₂-CL nanomotor effectively addresses key biological barriers in peri-implantitis, establishing a promising nanotherapeutic platform for biofilm-associated inflammatory diseases.