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.
Focused ultrasound (FUS) in combination with microbubbles is capable of noninvasive, site-targeted delivery of drugs through the blood-brain barrier (BBB). Although acoustic parameters are reproducible in small animals, their control remains challenging in primates due to skull heterogeneity. This study describes a 7-T magnetic resonance (MR)-guided FUS system designed for BBB disruption in non-human primates (NHP) with a robust feedback control based on passive cavitation detection (PCD). Contrast enhanced T-weighted MR images confirmed the BBB opening in NHP sonicated during 2 min with 500-kHz frequency, pulse length of 10 ms, and pulse repetition frequency of 5 Hz. The safe acoustic pressure range from 185 ± 22 kPa to 266 ± 4 kPa in one representative case was estimated from combining data from the acoustic beam profile with the BBB opening and hemorrhage profiles obtained from MR images. A maximum amount of MR contrast agent at focus was observed at 30 min after sonication with a relative contrast enhancement of 67% ± 15% (in comparison to that found in muscles). The feedback control based on PCD using relative spectra was shown to be robust, allowing comparisons across animals and experimental sessions. Finally, we also demonstrated that PCD can test acoustic coupling conditions, which improves the efficacy and safety of ultrasound transmission into the brain.
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