In Vitro Study on the Piezodynamic Therapy with a BaTiO₃-Coating Titanium Scaffold under Low-Intensity Pulsed Ultrasound Stimulation

Abstract

To solve the poor sustainability of electroactive stimulation in clinical therapy, a strategy of combining a piezoelectric BaTiO 3 -coated Ti6Al4V scaffold and lowintensity pulsed ultrasound (LIPUS) was unveiled and named here as piezodynamic therapy. Thus, cell behavior could be regulated phenomenally by force and electricity simultaneously. First, BaTiO 3 was deposited uniformly on the surface of the threedimensional (3D) printed porous Ti6Al4V scaffold, which endowed the scaffold with excellent force−electricity responsiveness under pulsed ultrasound exposure. The results of live/dead staining, cell scanning electron microscopy, and F-actin staining showed that cells had better viability, better pseudo-foot adhesion, and more muscular actin bundles when they underwent the piezodynamic effect of ultrasound and piezoelectric coating. This piezodynamic therapy activated more mitochondria at the initial stage that intervened in the cell cycle by promoting cells' proliferation and weakened the apoptotic damage. The quantitative real-time polymerase chain reaction data further confirmed that the costimulation of the ultrasound and the piezoelectric scaffolds could trigger adequate current to upregulated the expression of osteogenic-related genes. The continuous electric cues could be generated by the BaTiO 3 -coated scaffold and intermittent LIPUS stimulation; thereon, more efficient bone healing would be promoted by piezodynamic therapy in future treatment.

3D-Printed Piezoelectric Porous Bioactive Scaffolds and Clinical Ultrasonic Stimulation Can Help in Enhanced Bone Regeneration

“…In all the cases, the cells approvingly adhere and spread on the surface with flattened morphology, signifying that the PCL-BT scaffolds exhibit a bioactive and biocompatible surface. The increasing cell adherence and spread over the composites with increasing BaTiO 3 concentration demonstrate that the scaffold-generated piezoelectric effect played a major role in cell spreading [ 50 ]. The increasing BaTiO 3 particles enhance the piezoelectric effect, which helps the cells to proliferate and spread more rapidly on the scaffold surfaces.…”

“…The same research group performed another study in a large animal model (sheep) and confirmed that LIPUS induces a piezoelectric response from BaTiO 3 particles, leading to an increased cellular response in vitro and treating sizeable segmental bone defects in vivo [ 54 ]. Recently, Chen et al [ 50 ] also used LIPUS on the BaTiO 3 -coated Ti scaffold and coined the new term “piezodynamic therapy” for such kinds of treatment. The authors observed that the piezodynamic effect of US and piezoelectric BaTiO 3 coating activated more mitochondria at the initial stages of cell culture that intervened in the cell culture cycle by promoting cell proliferation and weakening the apoptotic damage.…”

Nanostructure Mediated Piezoelectric Effect of Tetragonal BaTiO3 Coatings on Bone Mesenchymal Stem Cell Shape and Osteogenic Differentiation

“…In recent years, much emphasis has been placed on building BaTiO 3 coatings on Ti porous scaffolds to promote bone regeneration [ 19 , 20 , 21 , 22 ]. Unfortunately, most studies did not explore the phase transition of the BaTiO 3 coatings, and none developed a nanostructured BaTiO 3 coating [ 19 , 20 , 21 , 22 ].…”

“…In recent years, much emphasis has been placed on building BaTiO 3 coatings on Ti porous scaffolds to promote bone regeneration [ 19 , 20 , 21 , 22 ]. Unfortunately, most studies did not explore the phase transition of the BaTiO 3 coatings, and none developed a nanostructured BaTiO 3 coating [ 19 , 20 , 21 , 22 ]. It is well-established that bulk BaTiO 3 can be easily manipulated to exhibit tetragonal ferroelectricity at room temperature, which is gradually reduced with decreasing particle size and disappears below a certain threshold (in the range of 10–100 nm) [ 23 ].…”

3D-printed Strontium-Titanium Scaffolds Incorporated with Highly Bioactive Serum Exosomes Promotes Critical Bone Defect Repair by Enhancing Osteogenesis and Angiogenesis

“…Recently, 3D-printed titanium (Ti) scaffolds have been increasingly utilized for customized treatment of large bone defects [3]. However, there are still many challenges to be overcome, before satisfactory osseointegration can be achieved, mainly due to the inherent bio-inertness and lack of osteoinductivity of titanium [4].…”