A Wireless Near-Infrared Spectroscopy Device for Flap Monitoring: Proof of Concept in a Porcine Musculocutaneous Flap Model.

BACKGROUND: Current near-infrared spectroscopy (NIRS)-based systems for continuous flap monitoring are highly sensitive for detecting malperfusion. However, the clinical utility and user experience are limited by the wired connection between the sensor and bedside console. This wire leads to instability of the flap-sensor interface and may cause false alarms. METHODS: We present a novel wearable wireless NIRS sensor for continuous fasciocutaneous free flap monitoring. This waterproof silicone-encapsulated Bluetooth-enabled device contains two light-emitting diodes and two photodetectors in addition to a battery sufficient for 5 days of uninterrupted function. This novel device was compared with a ViOptix T.Ox monitor in a porcine rectus abdominus myocutaneous flap model of arterial and venous occlusions. RESULTS: Devices were tested in four flaps using three animals. Both devices produced very similar tissue oxygen saturation (StO2) tracings throughout the vascular clamping events, with obvious and parallel changes occurring on arterial clamping, arterial release, venous clamping, and venous release. Small interdevice variations in absolute StO2 value readings and magnitude of change were observed. The normalized cross-correlation at zero lag describing correspondence between the novel NIRS and T.Ox devices was >0.99 in each trial. CONCLUSION: The wireless NIRS flap monitor is capable of detecting StO2 changes resultant from arterial vascular occlusive events. In this porcine flap model, the functionality of this novel sensor closely mirrored that of the T.Ox wired platform. This device is waterproof, highly adhesive, skin conforming, and has sufficient battery life to function for 5 days. Clinical testing is necessary to determine if this wireless functionality translates into fewer false-positive alarms and a better user experience.

Rapid continuous 3D printing of customizable peripheral nerve guidance conduits.

Engineered nerve guidance conduits (NGCs) have been demonstrated for repairing peripheral nerve injuries. However, there remains a need for an advanced biofabrication system to build NGCs with complex architectures, tunable material properties, and customizable geometrical control. Here, a rapid continuous 3D-printing platform was developed to print customizable NGCs with unprecedented resolution, speed, flexibility, and scalability. A variety of NGC designs varying in complexity and size were created including a life-size biomimetic branched human facial NGC. In vivo implantation of NGCs with microchannels into complete sciatic nerve transections of mouse models demonstrated the effective directional guidance of regenerating sciatic nerves via branching into the microchannels and extending toward the distal end of the injury site. Histological staining and immunostaining further confirmed the progressive directional nerve regeneration and branching behavior across the entire NGC length. Observational and functional tests, including the von Frey threshold test and thermal test, showed promising recovery of motor function and sensation in the ipsilateral limbs grafted with the 3D-printed NGCs.

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

High throughput direct 3D bioprinting in multiwell plates.

Advances in three dimensional (3D) bioprinting have enabled the fabrication of sophisticated 3D tissue scaffolds for biological and medical applications, where high speed, high throughput production in well plates is a critical need. Here, we present an integrated 3D bioprinting platform based on microscale continuous optical printing, capable of high throughputin siturapid fabrication of complex 3D biomedical samples in multiwell plate formats for subsequent culture and analysis. Our high throughput 3D bioprinter (HT-3DP) was used to showcase constructs of varying spatial geometries of biomimetic significance, tunable mechanical properties, as well as reproducibility. Live hepatocellular carcinoma 3D tissue scaffolds were fabricatedin situin multiwell plates, after which a functional drug response assay against the chemotherapy drug doxorubicin was performed. Dual cell-type populations involving both live hepatocellular carcinoma as well as human umbilical vein endothelial cells were also printed to demonstrate dual-tissue fabrication capability. This work demonstrates a significant advancement in that the production rate of 3D bioprinted tissue scaffolds with controllable spatial architectures and mechanical properties can now be done on a high throughput scale, enabling rapid generation ofin vitro3D tissue models within conventional multiwell cell culture plates for high throughput preclinical drug screening and disease modeling.

Performance Evaluation of a Wearable Tattoo Electrode Suitable for High-Resolution Surface Electromyogram Recording.

OBJECTIVE: High-density surface electromyography (HD-sEMG) has been utilized extensively in neuromuscular research. Despite its potential advantages, limitations in electrode design have largely prevented widespread acceptance of the technology. Commercial electrodes have limited spatial fidelity, because of a lack of sharpness of the signal, and variable signal stability. We demonstrate here a novel tattoo electrode that addresses these issues. Our dry HD electrode grid exhibits remarkable deformability which ensures superior conformity with the skin surface, while faithfully recording signals during different levels of muscle contraction. METHOD: We fabricated a 4 cm×3 cm tattoo HD electrode grid on a stretchable electronics membrane for sEMG applications. The grid was placed on the skin overlying the biceps brachii of healthy subjects, and was used to record signals for several hours while tracking different isometric contractions. RESULTS: The sEMG signals were recorded successfully from all 64 electrodes across the grid. These electrodes were able to faithfully record sEMG signals during repeated contractions while maintaining a stable baseline at rest. During voluntary contractions, broad EMG frequency content was preserved, with accurate reproduction of the EMG spectrum across the full signal bandwidth. CONCLUSION: The tattoo grid electrode can potentially be used for recording high-density sEMG from skin overlying major limb muscles. Layout programmability, good signal quality, excellent baseline stability, and easy wearability make this electrode a potentially valuable component of future HD electrode grid applications. SIGNIFICANCE: The tattoo electrode can facilitate high fidelity recording in clinical applications such as tracking the evolution and time-course of challenging neuromuscular degenerative disorders.

Wireless, implantable catheter-type oximeter designed for cardiac oxygen saturation.

Accurate, real-time monitoring of intravascular oxygen levels is important in tracking the cardiopulmonary health of patients after cardiothoracic surgery. Existing technologies use intravascular placement of glass fiber-optic catheters that pose risks of blood vessel damage, thrombosis, and infection. In addition, physical tethers to power supply systems and data acquisition hardware limit freedom of movement and add clutter to the intensive care unit. This report introduces a wireless, miniaturized, implantable optoelectronic catheter system incorporating optical components on the probe, encapsulated by soft biocompatible materials, as alternative technology that avoids these disadvantages. The absence of physical tethers and the flexible, biocompatible construction of the probe represent key defining features, resulting in a high-performance, patient-friendly implantable oximeter that can monitor localized tissue oxygenation, heart rate, and respiratory activity with wireless, real-time, continuous operation. In vitro and in vivo testing shows that this platform offers measurement accuracy and precision equivalent to those of existing clinical standards.

Bioresorbable Multilayer Photonic Cavities as Temporary Implants for Tether-Free Measurements of Regional Tissue Temperatures.

Objective and Impact Statement. Real-time monitoring of the temperatures of regional tissue microenvironments can serve as the diagnostic basis for treating various health conditions and diseases. Introduction. Traditional thermal sensors allow measurements at surfaces or at near-surface regions of the skin or of certain body cavities. Evaluations at depth require implanted devices connected to external readout electronics via physical interfaces that lead to risks for infection and movement constraints for the patient. Also, surgical extraction procedures after a period of need can introduce additional risks and costs. Methods. Here, we report a wireless, bioresorbable class of temperature sensor that exploits multilayer photonic cavities, for continuous optical measurements of regional, deep-tissue microenvironments over a timeframe of interest followed by complete clearance via natural body processes. Results. The designs decouple the influence of detection angle from temperature on the reflection spectra, to enable high accuracy in sensing, as supported by in vitro experiments and optical simulations. Studies with devices implanted into subcutaneous tissues of both awake, freely moving and asleep animal models illustrate the applicability of this technology for in vivo measurements. Conclusion. The results demonstrate the use of bioresorbable materials in advanced photonic structures with unique capabilities in tracking of thermal signatures of tissue microenvironments, with potential relevance to human healthcare.