High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research. High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks, and tracking fast pathophysiological activities at the microvessel level, which will enable advances in current queries in neurovascular and brain metabolism research, including stroke, dementia, and acute brain injury. Further, real-time imaging of oxygen saturation of hemoglobin (sO₂) can capture fast-paced oxygen delivery dynamics, which is needed to solve pertinent questions in these fields and beyond. Here, we present a novel ultrafast functional photoacoustic microscopy (UFF-PAM) to image the whole-brain hemodynamics and oxygenation. UFF-PAM takes advantage of several key engineering innovations, including stimulated Raman scattering (SRS) based dual-wavelength laser excitation, water-immersible 12-facet-polygon scanner, high-sensitivity ultrasound transducer, and deep-learning-based image upsampling. A volumetric imaging rate of 2 Hz has been achieved over a field of view (FOV) of 11 × 7.5 × 1.5 mm³ with a high spatial resolution of ~10 μm. Using the UFF-PAM system, we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia, sodium nitroprusside, and stroke. We observed the mouse brain’s fast morphological and functional changes over the entire cortex, including vasoconstriction, vasodilation, and deoxygenation. More interestingly, for the first time, with the whole-brain FOV and micro-vessel resolution, we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization (SD) wave. We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.

Electronic visual prostheses, or biomimetic eyes, have shown the feasibility of restoring functional vision in the blind through electrical pulses to initiate neural responses artificially. However, existing visual prostheses predominantly use wired connections or electromagnetic waves for powering and data telemetry, which raises safety concerns or couples inefficiently to miniaturized implant units. Here, we present a flexible ultrasound-induced retinal stimulating piezo-array that can offer an alternative wireless artificial retinal prosthesis approach for evoking visual percepts in blind individuals. The device integrates a two-dimensional piezo-array with 32-pixel stimulating electrodes in a flexible printed circuit board. Each piezo-element can be ultrasonically and individually activated, thus, spatially reconfigurable electronic patterns can be dynamically applied via programmable ultrasound beamlines. As a proof of concept, we demonstrate the ultrasound-induced pattern reconstruction in ex vivo murine retinal tissue, showing the potential of this approach to restore functional, life-enhancing vision in people living with blindness.

Clinical approaches for cancer therapy face several interrelated challenges involving inefficient drug delivery, potential adverse side effects, and inconvenience. Here, we present an integrated wearable flexible ultrasound microneedle patch (wf-UMP) that serves as a portable platform for convenient, efficient, and minimally invasive cancer therapy. The wf-UMP adopts an all-in-one bioelectronic concept, which integrates a stretchable lead-free ultrasound transducer array for acoustic emission, a bioadhesive hydrogel elastomer for robust adhesion and acoustic coupling, and a dissolvable microneedle patch loaded with biocompatible piezoelectric nanoparticles for painless drug delivery and reactive oxygen species generation. With soft mechanical properties and enhanced electromechanical performance, wf-UMP can be robustly worn on curved and dynamic tissue surfaces for easy and effective manipulation. In preclinical studies involving mice, wf-UMP demonstrated notable anticancer effects by inducing tumor cell apoptosis, amplifying oxidative stress, and modulating immune cell proliferation. Furthermore, the synergistic immunotherapy induced by wf-UMP and Anti-PD1 further improved anticancer immunity by activating immunogenic cell death and regulating macrophages polarization, inhibiting distant tumor growth and tumor recurrence.

Biodegradable piezoelectric devices hold great promise in on-demand transient bioelectronics. Existing piezoelectric biomaterials, however, remain obstacles to the development of such devices due to difficulties in large-scale crystal orientation alignment and weak piezoelectricity. Here, we present a strategy for the synthesis of optimally orientated, self-aligned piezoelectric γ-glycine/polyvinyl alcohol (γ-glycine/PVA) films via an ultrasound-assisted process, guided by density functional theory. The first-principles calculations reveal that the negative piezoelectric effect of γ-glycine originates from the stretching and compression of glycine molecules induced by hydrogen bonding interactions. The synthetic γ-glycine/PVA films exhibit a piezoelectricity of 10.4 picocoulombs per newton and an ultrahigh piezoelectric voltage coefficient of 324 × 10 ⁻³ volt meters per newton. The biofilms are further developed into flexible, bioresorbable, wireless piezo-ultrasound electrotherapy devices, which are demonstrated to shorten wound healing by ~40% and self-degrade in preclinical wound models. These encouraging results offer reliable approaches for engineering piezoelectric biofilms and developing transient bioelectronics.

The performance of ultrasonic transducers is largely determined by the piezoelectric properties and geometries of their active elements. Due to the brittle nature of piezoceramics, existing processing tools for piezoelectric elements only achieve simple geometries, including flat disks, cylinders, cubes and rings. While advances in additive manufacturing give rise to free-form fabrication of piezoceramics, the resultant transducers suffer from high porosity, weak piezoelectric responses, and limited geometrical flexibility. We introduce optimized piezoceramic printing and processing strategies to produce highly responsive piezoelectric microtransducers that operate at ultrasonic frequencies. The 3D printed dense piezoelectric elements achieve high piezoelectric coefficients and complex architectures. The resulting piezoelectric charge constant, d₃₃, and coupling factor, k_t, of the 3D printed piezoceramic reach 583 pC/N and 0.57, approaching the properties of pristine ceramics. The integrated printing of transducer packaging materials and 3D printed piezoceramics with microarchitectures create opportunities for miniaturized piezoelectric ultrasound transducers capable of acoustic focusing and localized cavitation within millimeter-sized channels, leading to miniaturized ultrasonic devices that enable a wide range of biomedical applications.

Bionic multifunctional structural materials that are lightweight, strong, and perceptible have shown great promise in sports, medicine, and aerospace applications. However, smart monitoring devices with integrated mechanical protection and piezoelectric induction are limited. Herein, we report a strategy to grow the recyclable and healable piezoelectric Rochelle salt crystals in 3D-printed cuttlebone-inspired structures to form a new composite for reinforcement smart monitoring devices. In addition to its remarkable mechanical and piezoelectric performance, the growth mechanisms, the recyclability, the sensitivity, and repairability of the 3D-printed Rochelle salt cuttlebone composite were studied. Furthermore, the versatility of composite has been explored and applied as smart sensor armor for football players and fall alarm knee pads, focusing on incorporated mechanical reinforcement and electrical self-sensing capabilities with data collection of the magnitude and distribution of impact forces, which offers new ideas for the design of next-generation smart monitoring electronics in sports, military, aerospace, and biomedical engineering.