Hierarchical\nChitin Nanocrystal-Based 3D Printed Dual-Layer\nMembranes Hydrogels: A Dual Drug Delivery Nano-Platform for Periodontal\nTissue Regeneration

Periodontitis,\na prevalent chronic inflammatory disease caused\nby bacteria, poses a significant challenge to current treatments by\nmerely slowing their progression. Herein, we propose an innovative\nsolution in the form of hierarchical nanostructured 3D printed bilayer\nmembranes that serve as dual-drug delivery nanoplatforms and provide\nscaffold function for the regeneration of periodontal tissue. Nanocomposite\nhydrogels were prepared by combining lipid nanoparticle-loaded grape\nseed extract and simvastatin, as well as chitin nanocrystals, which\nwere then 3D printed into a bilayer membrane that possesses antimicrobial\nproperties and multiscale porosity for periodontal tissue regeneration.\nThe constructs exhibited excellent mechanical properties by adding\nchitin nanocrystals and provided a sustained release of distinct drugs\nover 24 days. We demonstrated that the bilayer membranes are cytocompatible\nand have the ability to induce bone-forming markers in human mesenchymal\nstem cells, while showing potent antibacterial activity against pathogens\nassociated with periodontitis. <i>In vivo</i> studies further\nconfirmed the efficacy of bilayer membranes in enhancing alveolar\nbone regeneration and reducing inflammation in a periodontal defect\nmodel. This approach suggests promising avenues for the development\nof implantable constructs that not only combat infections, but also\npromote the regeneration of periodontal tissue, providing valuable\ninsights into advanced periodontitis treatment strategies.