Novel GSK-3 inhibitor based universal dentin bonding system: A comprehensive analysis of dentinal repair and improved bond strength

Abstract

The aim of the study was to describe the formulation of a novel universal adhesive system, based on a GSK-3 (glycogen synthetase kinase-3) inhibitor (Tideglusib®), and to evaluate its bond strength and dentinal repair capability. Tideglusib® was added to Ultradent Peak Universal Dentin Bonding Agent to make experimental adhesives (0.5 %, 1 %, 2 % final concentration). They were applied to teeth which were sectioned, stored for 24 h, or 2 years then bond strengths measured. Baseline stiffness of bonded dentin beams was tested using the three-point bending test. Animal experiments were performed to provide specimens for microcomputed tomography imaging after adhesive application. Collagen matrix was evaluated using transmission electron microscopy. The cytotoxicity of the modified adhesives was determined using fibroblastic cells. Molecular modelling evaluated binding of the Tideglusib® molecule to active sites on collagen and the adhesive components. TGFβ-1/and BMP-2 in human dentin matrices were measured and interfaces were scanned using SkyScan 2211. Adhesives’ stability tests were done. ResultsRMSD (root mean square deviation) analysis indicated simulation has equilibrated with changes for globular proteins (p < 0.05). Specimens from 0.5 %, and 1 % Tideglusib® groups displayed adhesive penetration with Micro-CT imaging and a significant increase in dentin density was seen. Specimens from the same groups showed cells with large masses of cytoplasm with focal adhesion points. Bond strength decreased significantly (p < 0.05) with increased storage time. Gradual release (p < 0.05) of both TGFβ-1 and BMP-2 from hTDMs with 0.5 % and 1 % Tideglusib® groups occurred and higher elastic moduli (p < 0.05). Collagen-based amide and proline Raman bands were seen in the Tideglusib® groups. ConclusionIncorporation of Tideglusib® in experimental Universal Adhesive System at 1 % improved adhesive bond strength and promoted dentinal repair. Application of Tideglusib® based adhesive conserve mechanical properties of the tooth structure and promote regenerative capability so can be expected to extend the service life of adhesive restorations in clinical situations.