Biomimetic MoSe2 Nanozymes Boost Implant Soft Tissue Healing on Two Fronts

Dental implants have transformed modern dentistry, yet their long-term success remains quietly under siege. While titanium fixtures reliably fuse with bone, the soft tissue seal that surrounds each implant is far more fragile. Epidemiological studies cited in the new work suggest that 17 to 24 percent of implant patients eventually develop peri-implantitis, and 41 to 51 percent experience the milder but still damaging peri-implant mucositis. The economic toll is staggering: global spending on peri-implantitis treatment alone reached 1.04 billion US dollars in 2024 and is projected to grow at 9.1 percent annually through 2030. Now, a team reporting in Advanced Science has unveiled a biomimetic nanoplatform that attacks the root causes of this failure on two fronts simultaneously, and its results in rats are striking.

The core insight behind the study is that soft tissue breakdown around implants is not simply a matter of insufficient attachment. Instead, the researchers describe an early pathogenic-immunological amplification loop. Staphylococcus aureus, a bacterium with a particular affinity for titanium surfaces, is among the first colonizers of a fresh implant. Its accumulation, combined with surgical trauma and implant-induced oxidative stress, drives macrophages into a dysfunctional, pro-inflammatory state. Sustained inflammatory signaling then damages fibroblasts, impairs extracellular matrix remodeling, and blocks vascular maturation, all of which undermine the connective tissue barrier that should protect the implant. Disrupting this loop, the authors reasoned, requires a therapy that can target both the bacterium and the stressed immune cells at the same time.

Their solution, called MoSe2@SPMM, is a two-layer construction. At its heart sits a molybdenum diselenide nanoflower, a member of the nanozyme family of artificial enzyme mimics. MoSe2 carries intrinsic multi-enzyme catalytic activity that scavenges reactive oxygen species, mimicking catalase, glutathione peroxidase, and superoxide dismutase. It also converts near-infrared light into heat efficiently, and the material’s molybdenum and selenium components are individually associated with favorable biocompatibility. Wrapped around this reactive core is a cell membrane shell harvested from macrophages that had been deliberately pre-stimulated with S. aureus. The coating is applied through ultrasonication and extrusion, leaving a continuous membranous shell visible in transmission electron microscopy around a particle roughly 218 nanometers in hydrodynamic diameter before coating.

The choice of a bacteria-stimulated membrane is the study’s most elegant twist. Proteomic profiling of macrophages after S. aureus exposure revealed 534 upregulated and 235 downregulated proteins, with enrichment overwhelmingly concentrated in bacterial recognition, pattern-recognition-receptor signaling, and Toll-like receptor pathways. Follow-up transcriptional and protein analyses showed that TLR2, TLR6, and the scavenger receptor CD36 were selectively upregulated on the macrophage membrane, while virus-associated receptors stayed flat. When these membranes were transferred onto MoSe2, Western blots confirmed the nanoparticles retained elevated levels of all three recognition molecules. The result is a nanoparticle dressed in a molecular disguise that bacteria find irresistible to bind, and one that other macrophages recognize as kin.

Laboratory testing bore out the dual-targeting hypothesis. Compared with nanoparticles coated in unstimulated macrophage membranes, red blood cell membranes, or synthetic DOPC lipid shells, MoSe2@SPMM showed dramatically stronger binding to S. aureus in both scanning electron and confocal microscopy, while showing no such preference for E. coli, a sign of genuine selectivity. When near-infrared light at 808 nanometers was applied, the bound particles converted light to heat at the bacterial surface, producing what the authors call targeted contact-enhanced photothermal killing. Bacterial membranes roughened, perforated, and collapsed, and colony assays showed the treatment dramatically outperformed controls. Against biofilms, which are far more resistant and clinically relevant, the particles not only suppressed formation but also disrupted established structures, killing bacteria throughout the biofilm depth rather than only at the surface.

The second axis of action operates inside immune cells. Because the coating carries homotypic recognition features, MoSe2@SPMM is preferentially internalized by macrophages themselves, while fibroblasts and endothelial cells take up far less of it. Once inside oxidative-stress-injured macrophages, the nanoparticle’s enzymatic core mops up excess reactive oxygen species. In vitro, the particles removed roughly 75 to 88 percent of hydrogen peroxide within an hour at moderate concentrations, generated dissolved oxygen, and quenched both superoxide and hydroxyl radicals in electron spin resonance assays, with activity persisting over repeated catalytic cycles. In cells, treatment lowered intracellular ROS, restored mitochondrial membrane potential, suppressed the pro-inflammatory marker iNOS, revived the repair-associated marker Arg-1, and shifted the secretome away from TNF-alpha and IL-6 toward IL-10 and TGF-beta.

Those cellular changes rippled outward to the tissue-building cells that determine whether a soft tissue seal can form. Conditioned medium from MoSe2@SPMM-treated macrophages restored the proliferation, migration, and tube-forming capacity of vascular endothelial cells under oxidative stress, accompanied by recovered expression of VEGF-A and FGF2, two master regulators of angiogenesis. Fibroblasts responded similarly, regaining migration and adhesion while rebuilding focal adhesion protein vinculin, fibronectin 1, and both collagen I and collagen III, the structural foundation of the peri-implant connective tissue. Biosafety testing was reassuring: the particles were compatible with cells up to 200 micrograms per milliliter, caused negligible hemolysis, and produced no histological, hematological, or liver and kidney abnormalities in treated animals.

The decisive test came in a rat maxillary implantation model in which S. aureus was inoculated at the peri-implant site to simulate early post-surgical stress. Under localized near-infrared irradiation, MoSe2@SPMM reduced the peri-implant bacterial burden by 91.4 percent, substantially outperforming both control coatings. Immunofluorescence at day 7 showed a marked shift in macrophage identity, with fewer iNOS-positive pro-inflammatory cells and more Arg-1-positive repair-associated cells. By day 28, the treated implants displayed denser alpha-SMA-positive vascular maturation, a 1.7-fold increase in peri-implant connective tissue width, 67.1 percent greater collagen deposition with better fiber organization, 61.4 percent higher integrin expression at the tissue-implant interface, and a 2.3-fold increase in angiogenesis. The animals developed a continuous epithelial barrier and reduced inflammatory infiltration, hallmarks of robust soft tissue integration.

What distinguishes this platform from conventional implant surface engineering is its mode of delivery and breadth of function. Surface-bound coatings fight a losing battle against the oral environment, gradually losing bioactivity and offering only single-function protection. MoSe2@SPMM, by contrast, is designed for local administration at the implant-soft tissue interface, potentially injected around the transgingival neck during early healing or under high-risk inflammatory conditions, then activated with intraoral near-infrared probes. The authors also suggest the design principle could extend beyond dentistry to orthopedic and percutaneous devices, wherever bacterial colonization, oxidative stress, and dysregulated inflammation jointly sabotage tissue repair.

Challenges remain before clinical translation. The rat model used controlled S. aureus inoculation rather than the polymicrobial biofilms characteristic of established human peri-implantitis, so real-world efficacy will need confirmation in more complex settings. Optimal treatment windows, irradiation parameters, repeat dosing schedules, and scalable membrane-coating manufacturing all require refinement. Yet the conceptual achievement is clear: by teaching a nanoparticle to hunt one specific bacterium and simultaneously nurse the immune cells back to health, the researchers have demonstrated that targeted antibacterial action and redox-mediated immune regulation can be fused into a single therapy, offering a genuinely new strategy for protecting the fragile seal on which every dental implant ultimately depends.

Subject of Research: Dual-targeted biomimetic MoSe2 nanozymes coated with S. aureus-stimulated macrophage membranes for enhancing peri-implant soft tissue integration

Article Title: Dual‐Targeted Biomimetic MoSe2 Nanozymes for Enhancing Peri‐Implant Soft Tissue Integration

Article References: Zhou, M., Tian, M., Yu, J., Kang, J., Chen, M., Yuan, Y., Liu, L., & Wei, H. (2026). Dual‐Targeted Biomimetic MoSe 2 Nanozymes for Enhancing Peri‐Implant Soft Tissue Integration. Advanced Science, Article e77771. https://doi.org/10.1002/advs.77771

Image Credits: AI Generated

DOI: 10.1002/advs.77771

Keywords: MoSe2 nanozymes, peri-implantitis, soft tissue integration, biomimetic nanoparticles, cell membrane coating, Staphylococcus aureus, photothermal therapy, macrophage reprogramming, reactive oxygen species, dental implants, immunomodulation, oxidative stress