Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.

To date, a wide variety of neural tissue implants have been developed for neurophysiology recording from living tissues. An ideal neural implant should minimize the damage to the tissue and perform reliably and accurately for long periods of time. Therefore, the materials utilized to fabricate the neural recording implants become a critical factor. The materials of these devices could be classified into two broad categories: electrode materials as well as packaging and substrate materials. In this review, inorganic (metals and semiconductors), organic (conducting polymers), and carbon-based (graphene and carbon nanostructures) electrode materials are reviewed individually in terms of various neural recording devices that are reported in recent years. Properties of these materials, including electrical properties, mechanical properties, stability, biodegradability/bioresorbability, biocompatibility, and optical properties, and their critical importance to neural recording quality and device capabilities, are discussed. For the packaging and substrate materials, different material properties are desired for the chronic implantation of devices in the complex environment of the body, such as biocompatibility and moisture and gas hermeticity. This review summarizes common solid and soft packaging materials used in a variety of neural interface electrode designs, as well as their packaging performances. Besides, several biopolymers typically applied over the electrode package to reinforce the mechanical rigidity of devices during insertion, or to reduce the immune response and inflammation at the device-tissue interfaces are highlighted. Finally, a benchmark analysis of the discussed materials and an outlook of the future research trends are concluded.

This article reviews recent developments in miniaturized neural implants for optogenetics, highlights major improvements enabled by microtechnologies, and discusses challenges faced by developers and adopters of these new technologies.

The recent development of optogenetics has created an increased demand for advancing engineering tools for optical modulation of neural circuitry. This paper details the design, fabrication, integration, and packaging procedures of a wirelessly-powered, light emitting diode (LED) coupled optrode neural interface for optogenetic studies. The LED-coupled optrode array employs microscale LED (μLED) dies and polymer-based microwaveguides to deliver light into multi-level cortical networks, coupled with microelectrodes to record spontaneous changes in neural activity. An integrated, implantable, switched-capacitor based stimulator (SCS) system provides high instantaneous power to the μLEDs through an inductive link to emit sufficient light and evoke neural activities. The presented system is mechanically flexible, biocompatible, miniaturized, and lightweight, suitable for chronic implantation in small freely behaving animals. The design of this system is scalable and its manufacturing is cost effective through batch fabrication using microelectromechanical systems (MEMS) technology. It can be adopted by other groups and customized for specific needs of individual experiments.

Diamond possesses many favorable properties for biochemical sensors, including biocompatibility, chemical inertness, resistance to biofouling, an extremely wide potential window, and low double-layer capacitance. The hardness of diamond, however, has hindered its applications in neural implants due to the mechanical property mismatch between diamond and soft nervous tissues. Here, we present a flexible, diamond-based microelectrode probe consisting of multichannel boron-doped polycrystalline diamond (BDD) microelectrodes on a soft Parylene C substrate. We developed and optimized a wafer-scale fabrication approach that allows the use of the growth side of the BDD thin film as the sensing surface. Compared to the nucleation surface, the BDD growth side exhibited a rougher morphology, a highersp³content, a wider water potential window, and a lower background current. The dopamine (DA) sensing capability of the BDD growth surface electrodes was validated in a 1.0 mM DA solution, which shows better sensitivity and stability than the BDD nucleation surface electrodes. The results of these comparative studies suggest that using the BDD growth surface for making implantable microelectrodes has significant advantages in terms of the sensitivity, selectivity, and stability of a neural implant. Furthermore, we validated the functionality of the BDD growth side electrodes for neural recordings both in vitro and in vivo. The biocompatibility of the microcrystalline diamond film was also assessed in vitro using rat cortical neuron cultures.

Distributed neural interfaces made of many mm-sized implantable medical devices (IMDs) are poised to play a key role in future brain-computer interfaces because of less damage to the surrounding tissue. Evaluating them wirelessly at preclinical stage (e.g., in a rodent model), however, is a major challenge due to weak coupling and significant losses, resulting in limited power delivery to the IMD within a nominal experimental arena, like a homecage, without surpassing the specific absorption rate limit. To address this problem, we present a dual-band EnerCage system with two multi-coil inductive links, which first deliver power at 13.56 MHz from the EnerCage (46 × 24 × 20 cm ³ ) to a headstage (18 × 18 × 15 mm ³ , 4.8 g) that is carried by the animal via a 4-coil inductive link. Then, a 60 MHz 3-coil inductive link from the headstage powers up the small IMD (2.5 × 2.5 × 1.5 mm ³ , 15 mg), which in this case is a free floating, wirelessly powered, implantable optical stimulator (FF-WIOS). The power transfer efficiency and power delivered to the load (PDL) from EnerCage to the headstage at 7 cm height were 14.9%-22.7% and 122 mW; and from headstage to FF-WIOS at 5 mm depth were 18% and 2.7 mW, respectively. Bidirectional data connectivity between EnerCage-headstage was established via bluetooth low energy. Between headstage and FF-WIOS, on-off keying and load-shift-keying were used for downlink and uplink data, respectively. Moreover, a closed-loop power controller stabilized PDL to both the headstage and the FF-WIOS against misalignments.