Piezoelectric Nanomaterials Activated by Ultrasound: The Pathway from Discovery to Future Clinical Adoption

Abstract

Electrical stimulation has shown great promise in biomedical applications, such as regenerative medicine, neuromodulation, and cancer treatment. Yet, the use of electrical end effectors such as electrodes requires connectors and batteries, which dramatically hamper the translation of electrical stimulation technologies in several scenarios. Piezoelectric nanomaterials can overcome the limitations of current electrical stimulation procedures as they can be wirelessly activated by external energy sources such as ultrasound. Wireless electrical stimulation mediated by piezoelectric nanoarchitectures constitutes an innovative paradigm enabling the induction of electrical cues within the body in a localized, wireless, and minimally invasive fashion. In this review, we highlight the fundamental mechanisms of acoustically mediated piezoelectric stimulation and its applications in the biomedical area. Yet, the adoption of this technology in a clinical practice is in its infancy, as several open issues, such as piezoelectric properties measurement, control of the ultrasound dose in vitro , modeling and measurement of the piezo effects, knowledge on the triggered bioeffects, therapy targeting, biocompatibility studies, and control of the ultrasound dose delivered in vivo , must be addressed. This article explores the current open challenges in piezoelectric stimulation and proposes strategies that may guide future research efforts in this field toward the translation of this technology to the clinical scene.

Diaryliodonium salts facilitate metal-free mechanoredox free radical polymerizations

“…One mechanism to facilitate the use of force in chemical synthesis is mechanoredox catalysis 31 (Figure 1); the piezoelectric effect [32][33][34][35] converts mechanical energy into a usable electric potential. Many applications mirror bone growth 36 and mechanogenetics 24,37 mechanisms found in biological systems.…”

Ultrasound-activable piezoelectric membranes for accelerating wound healing

“…The ultrasound-activated membranes are able to produce localized electrical stimuli to the wound sites and trigger cell proliferation and migration at the wound edge, thereby accelerating skin regeneration. 45,51,52 These results indicate that the ultrasound-activable piezoelectric membranes are able to promote wound healing. The images of H&E staining of the tissues around the wounds in different groups are shown in Fig.…”

Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization

“…S3 ). Combining the biosafety issue together with electrical signal output, we selected LIPUS with parameters of 1 MHz and 1.0 W/cm 2 for follow-up research [ 24 , 30 ]. Strikingly, P-BTO nanoparticles recorded a two‐fold increase in open-circuit voltage (ca.…”

“…Piezoelectric materials have non-centrosymmetric crystalline structures, which could exhibit unique mechano-electrical behavior in response to external forces (e.g., compressions, vibrations, sounds), providing a potential non-invasive electrical stimulation tool. Piezoelectric nanoparticles are particularly beneficial because of their unique zero-dimensional structure, precisely tunable polarization properties, high spatial specificity and the ability to be phagocytosed into cells for intracellular action in a drug-like manner [ [22] , [23] , [24] ]. In this work, tetragonal polarized barium titanate (P-BTO) piezoelectric nanoparticles with high mechano-electrical conversion performance were developed for tumor vascular normalization.…”