TCPP/MgO-loaded PLGA microspheres combining photodynamic antibacterial therapy with PBM-assisted fibroblast activation to treat periodontitis.

Bacteria eradication and subsequent periodontal tissue reconstruction is the primary task for periodontitis treatment. Commonly used antibiotic therapy suffers from antibiotic resistance. Meanwhile, promoting fibroblast activity is crucial for re-establishing a damaged periodontal structure. In addition to the fibroblast activation property of Mg2+, photobiomodulation (PBM) has recently attracted increasing attention in wound healing. Using the same 635 nm laser resource, PBM could simultaneously work with antibacterial photodynamic therapy (aPDT) to achieve antibacterial function and fibroblast activation effect. Herein, multifunctional microspheres were designed by employing poly (lactic-co-glycolic acid) (PLGA) microspheres to load tetrakis (4-carboxyphenyl) porphyrin (TCPP) and magnesium oxide (MgO) nanoparticles, named as PMT, with sustained Mg2+ release for 20 days. PMT achieved excellent antibacterial photodynamic effect for periodontal pathogens F. nucleatum and P. gingivalis by generating reactive oxygen species, which increases cell membrane permeability and destroys bacteria integrity to cause bacteria death. Meanwhile, PMT itself exhibited improved fibroblast viability and adhesion, with the PMT + light group revealing further activation of fibroblast cells, suggesting the coordinated action of Mg2+ and PBM effects. The underlying molecular mechanism might be the elevated gene expressions of Fibronectin 1, Col1a1, and Vinculin. In addition, the in vivo rat periodontitis model proved the superior therapeutic effects of PMT with laser illumination using micro-computed tomography analysis and histological staining, which presented decreased inflammatory cells, increased collagen production, and higher alveolar bone level in the PMT group. Our study sheds light on a promising strategy to fight periodontitis using versatile microspheres, which combine aPDT and PBM-assisted fibroblast activation functions.

Metal-organic framework-based nanoplatform enhance fibroblast activity to treat periodontitis.

After periodontal tissue injury, reconstruct soft tissue sealing around the tooth surface is of fundamental importance to treat periodontitis. Among multiple cell types, fibroblast plays a central role in reestablishing functional periodontium. To enhance fibroblast activity, a novel metal-organic framework-based nanoplatform is fabricated using mesoporous Prussian blue (MPB) nanoparticles to load baicalein (BA), named MPB-BA. Drug release test displayed sustained BA release of MPB-BA. Cell proliferation, transwell migration and wound healing tests revealed accelerated fibroblast proliferation and migration for the established MPB-BA nanoplatform. Moreover, vinculin immunofluorescence staining, western blot and quantitative real-time PCR analysis showed up-regulated vinculin protein and integrin α5 and integrin ß1 gene expressions for MPB-BA, suggesting improved cell adhesion. In addition, hematoxylin and eosin (H&E) and Masson trichromatic staining suggested superior anti-inflammatory and collagen fiber reconstruction effects for MPB-BA in a rat experimental periodontitis model in vivo. Our study may provide a promising strategy for the treatment of periodontitis.

Photothermal-Controlled Release of IL-4 in IL-4/PDA-Immobilized Black Titanium Dioxide (TiO2) Nanotubes Surface to Enhance Osseointegration: An In Vivo Study.

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.