A Novel Injectable Piezoelectric Hydrogel for Periodontal Disease Treatment

Abstract

Periodontal disease is a multifactorial, bacterially induced inflammatory condition characterized by the progressive destruction of periodontal tissues. The successful nonsurgical treatment of periodontitis requires multifunctional technologies offering antibacterial therapies and promotion of bone regeneration simultaneously. For the first time, in this study, an injectable piezoelectric hydrogel (PiezoGEL) was developed after combining gelatin methacryloyl (GelMA) with biocompatible piezoelectric fillers of barium titanate (BTO) that produce electrical charges when stimulated by biomechanical vibrations (e.g., mastication, movements). We harnessed the benefits of hydrogels (injectable, light curable, conforms to pocket spaces, biocompatible) with the bioactive effects of piezoelectric charges. A thorough biomaterial characterization confirmed piezoelectric fillers' successful integration with the hydrogel, photopolymerizability, injectability for clinical use, and electrical charge generation to enable bioactive effects (antibacterial and bone tissue regeneration). PiezoGEL showed significant reductions in pathogenic biofilm biomass (∼41%), metabolic activity (∼75%), and the number of viable cells (∼2−3 log) compared to hydrogels without BTO fillers in vitro. Molecular analysis related the antibacterial effects to be associated with reduced cell adhesion (downregulation of porP and f imA) and increased oxidative stress (upregulation of oxyR) genes. Moreover, PiezoGEL significantly enhanced bone marrow stem cell (BMSC) viability and osteogenic differentiation by upregulating RUNX2, COL1A1, and ALP. In vivo, PiezoGEL effectively reduced periodontal inflammation and increased bone tissue regeneration compared to control groups in a mice model. Findings from this study suggest PiezoGEL to be a promising and novel therapeutic candidate for the treatment of periodontal disease nonsurgically.

EnduroBone: A 3D printed bioreactor for extended bone tissue culture

“…Despite the critical role of such combined stimulation to bone biology, an integrated bioreactor with perfusion and mechanical stimulation for 3D bone cultures is either lacking or significantly expensive, limiting its wide use. MechanoCulture TX and TR (Cell Scale, Canada) are such systems that can provide perfusion shear together with programmable hydrostatic compression up to 500 kPa to samples placed in tissue wells for different applications [11] , [12] , [13] , [14] . The transparent culture wells enable real-time imaging and are autoclavable for storage in an incubator.…”

Piezoelectric Hydrogels: Hybrid Material Design, Properties, and Biomedical Applications

“…[27,136,142] For example, Roldan et al reported an injectable PH composite using GelMA and biocompatible BTO fillers to promote antibacterial effects and alveolar bone tissue regeneration as a form of periodontal disease treatment. [143] Such an oral disease progressively erodes away at the periodontal tissues to ultimately result in teeth loss. However, the use of their PH injectable has reduced inflammation and the pocket depth of the periodontal area after just a month of treatment through the enhancement of early ECM mineralization, bone marrow stem cell (BMSC) viability, and osteogenic differentiation by upregulating osteogenesisrelated genes such as RUNX2, COL1A1, and ALP.…”

“…Copyright 2022, American Chemical Society. d-f) Wound healing and tissue regeneration evaluation of the GelMA/BTO injectable: d) schematic of periodontal disease treatment over the course of 30 d; e) graph demonstrating change in cementum-enamel junction; Reproduced with permission [140]. Copyright 2023, American Chemical Society.…”

Piezoelectric hydrogel for treatment of periodontitis through bioenergetic activation

“…Compared to conventional ES, piezoelectric stimulation presents unique advantages such as non-invasiveness, wireless manipulation, self-powered energy supply, and high spatiotemporal precision. Despite much attention has been paid to piezoelectricity-stimulated tissue regeneration (e.g., nerve, bone, periodontal tissues) [ [23] , [24] , [25] , [26] , [27] ], its capacity to simultaneously activate the bioenergetics of stem cells and modulate the immune microenvironment is overlooked [ 28 , 29 ].…”