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Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

Standard diagnostic ultrasound imaging procedures heavily rely on a sonographer for image acquisition. Given the ultrasound probe is manually manipulated by the sonographer, there is a potential for noise artifacts like blurry acquired images caused by involuntary hand movements. Certain surgical procedures can also cause patients to exhibit involuntary “jumping” movements while on the operating table leading to further deterioration in ultrasound image quality. In this study, we attempt to mitigate these problems by fabricating a 3D-printed ultrasound probe holder. Due to the lightweight nature of the device, it can attach to surgical retractors without influencing the functionality of the retractor. Therefore, the 3D printed probe holder not only reduces relative motion between the probe and the patient, but also reduce the need for a sonographer during complex surgeries.

More than 32.5 million American adults suffer from osteoarthritis, and current treatments including pain medicines and anti-inflammatory drugs only alleviate symptoms but do not cure the disease. Here, we have demonstrated that a biodegradable piezoelectric poly(L-lactic acid) (PLLA) nanofiber scaffold under applied force or joint load could act as a battery-less electrical stimulator to promote chondrogenesis and cartilage regeneration. The PLLA scaffold under applied force or joint load generated a controllable piezoelectric charge, which promoted extracellular protein adsorption, facilitated cell migration or recruitment, induced endogenous TGF-β via calcium signaling pathway, and improved chondrogenesis and cartilage regeneration both in vitro and in vivo. Rabbits with critical-sized osteochondral defects receiving the piezoelectric scaffold and exercise treatment experienced hyaline-cartilage regeneration and completely healed cartilage with abundant chondrocytes and type II collagen after 1 to 2 months of exercise (2 to 3 months after surgery including 1 month of recovery before exercise), whereas rabbits treated with nonpiezoelectric scaffold and exercise treatment had unfilled defect and limited healing. The approach of combining biodegradable piezoelectric tissue scaffolds with controlled mechanical activation (via physical exercise) may therefore be useful for the treatment of osteoarthritis and is potentially applicable to regenerating other injured tissues.

Piezoelectric materials, a type of “smart” material that generates electricity while deforming and vice versa, have been used extensively for many important implantable medical devices such as sensors, transducers, and actuators. However, commonly utilized piezoelectric materials are either toxic or nondegradable. Thus, implanted devices employing these materials raise a significant concern in terms of safety issues and often require an invasive removal surgery, which can damage directly interfaced tissues/organs. Here, we present a strategy for materials processing, device assembly, and electronic integration to 1) create biodegradable and biocompatible piezoelectric PLLA [poly(l-lactic acid)] nanofibers with a highly controllable, efficient, and stable piezoelectric performance, and 2) demonstrate device applications of this nanomaterial, including a highly sensitive biodegradable pressure sensor for monitoring vital physiological pressures and a biodegradable ultrasonic transducer for blood–brain barrier opening that can be used to facilitate the delivery of drugs into the brain. These significant applications, which have not been achieved so far by conventional piezoelectric materials and bulk piezoelectric PLLA, demonstrate the PLLA nanofibers as a powerful material platform that offers a profound impact on various medical fields including drug delivery, tissue engineering, and implanted medical devices.

Transcranial focused ultrasound stimulation is a neuromodulation technique that is capable of exciting or suppressing the neural network. Such neuro-modulatory effects enable the treatment of brain diseases non-invasively, such as treating stroke. The neuro-modulatory effect on cerebral hemodynamics has been monitored using laser speckle contrast imaging in animal studies. However, the bulky size and stationary nature of the imaging system constrains the application of this imaging technique on research that requires the animal to have different body positions or to be awake. We present the design of a system that combines a miniature microscope for laser speckle contrast imaging and transcranial focused ultrasound stimulation, as well as, test its capability to monitor cerebral hemodynamics during stimulation and compare the result with a benchtop imaging system.

Many surgeons are faced with inoperable or only partially operable brain lesions, such as tumors. Even when surgery is feasible, patient outcomes are greatly affected by blood loss or infection. This has led many physicians toward non- or minimally-invasive surgery, which demands specialized toolkits. Focused ultrasound has great potential for assisting in such procedures due to its ability to focus a few centimeters away from the surface of the transducer. In a prior study, we developed a focused ultrasound prototype that could fit within a BrainPath trocar, specifically made for minimally invasive brain surgery. Here, we present the design and fabrication of a second prototype that reduces size, is MR-compatible, and has electronic steering capabilities.

Cotton balls are a versatile and efficient tool commonly used in neurosurgical procedures to absorb fluids and manipulate delicate tissues. However, the use of cotton balls is accompanied by the risk of accidental retention in the brain after surgery. Retained cotton balls can lead to dangerous immune responses and potential complications, such as adhesions and textilomas. In a previous study, we showed that ultrasound can be safely used to detect cotton balls in the operating area due to the distinct acoustic properties of cotton compared with the acoustic properties of surrounding tissue. In this study, we enhance the experimental setup using a 3D-printed custom depth box and a Butterfly IQ handheld ultrasound probe. Cotton balls were placed in variety of positions to evaluate size and depth detectability limits. Recorded images were then analyzed using a novel algorithm that implements recently released YOLOv4, a state-of-the-art, real-time object recognition system. As per the radiologists’ opinion, the algorithm was able to detect the cotton ball correctly 61% of the time, at approximately 32 FPS. The algorithm could accurately detect cotton balls up to 5mm in diameter, which corresponds to the size of surgical balls used by neurosurgeons, making the algorithm a promising candidate for regular intraoperative use.

Efficiency and patient safety are top priorities in any surgical operation. One effective way to achieve these objectives is automating many of the logistical and routine tasks that occur in the operating room. Inspired by smart assistant technology already commonplace in the consumer sector, we engineered the Smart Hospital Assistant (SHA), a smart, voice-controlled virtual assistant that handles natural speech recognition while executing a plurality of functions to aid surgery. Simulated surgeries showed that the SHA reduced operating time, optimized surgical staff resources, and reduced the number of major touch points that can lead to surgical site infections. The SHA not only shows its potential in the operating room, but also in other healthcare environments that may benefit from having virtual smart assistant technology.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time, biodegradable, to avoid invasive removal surgery that can damage directly-interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important bio-physiological forces. Here, we present a new strategy for material processing, electromechanical analysis, device fabrication, and assessment of a new piezoelectric Poly-L-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force-sensor which only employs medical materials used commonly in FDA-approved implants, for the monitoring of biological forces

Repeated bolus injections are associated with higher costs and poor compliance and can hinder the implementation of global immunization campaigns. Here, we report the development and preclinical testing of patches of transdermal core-shell microneedles-which were fabricated by the micromoulding and alignment of vaccine cores and shells made from poly(lactic-co-glycolic acid) with varying degradability kinetics-for the preprogrammed burst release of vaccine payloads over a period of a few days to more than a month from a single administration. In rats, microneedles loaded with a clinically available vaccine (Prevnar-13) against the bacterium Streptococcus pneumoniae induced immune responses that were similar to immune responses observed after multiple subcutaneous bolus injections, and led to immune protection against a lethal bacterial dose. Microneedle patches delivering preprogrammed doses may offer an alternative strategy to prophylactic and therapeutic protocols that require multiple injections.

Recently, there has been an emerging interest in controlling 3D structures and designing novel 3D shapes for drug carriers at nano- and micro-scales. Certain 3D shapes and structures of drug particles enable transportation of the drugs to desired areas of the body, allow drugs to target specific cells and tissues, and influence release kinetics. Advanced nano- and micro-manufacturing methods including 3D printing, photolithography-based processes, microfluidics and DNA origami have been developed to generate defined 3D shapes and structures for drug carriers. This paper reviews the importance of 3D structures and shapes on controlled drug delivery, and the current state-of-the-art technologies that allow the creation of novel 3D drug carriers at nano- and micro-scales.

Electrical stimulation (ES) has been shown to induce and enhance bone regeneration. By combining this treatment with tissue-engineering approaches (which rely on biomaterial scaffolds to construct artificial tissues), a replacement bone-graft with strong regenerative properties can be achieved while avoiding the use of potentially toxic levels of growth factors. Unfortunately, there is currently a lack of safe and effective methods to induce electrical cues directly on cells/tissues grown on the biomaterial scaffolds. Here, we present a novel bone regeneration method which hybridizes ES and tissue-engineering approaches by employing a biodegradable piezoelectric PLLA (Poly(L-lactic acid)) nanofiber scaffold which, together with externally-controlled ultrasound (US), can generate surface-charges to drive bone regeneration. We demonstrate that the approach of using the piezoelectric scaffold and US can enhance osteogenic differentiation of different stem cells in vitro, and induce bone growth in a critical-sized calvarial defect in vivo. The biodegradable piezoelectric scaffold with applied US could significantly impact the field of tissue engineering by offering a novel biodegradable, battery-free and remotely-controlled electrical stimulator.

Recent advances in materials, manufacturing, biotechnology, and microelectromechanical systems (MEMS) have fostered many exciting biosensors and bioactuators that are based on biocompatible piezoelectric materials. These biodevices can be safely integrated with biological systems for applications such as sensing biological forces, stimulating tissue growth and healing, as well as diagnosing medical problems. Herein, the principles, applications, future opportunities, and challenges of piezoelectric biomaterials for medical uses are reviewed thoroughly. Modern piezoelectric biosensors/bioactuators are developed with new materials and advanced methods in microfabrication/encapsulation to avoid the toxicity of conventional lead-based piezoelectric materials. Intriguingly, some piezoelectric materials are biodegradable in nature, which eliminates the need for invasive implant extraction. Together, these advancements in the field of piezoelectric materials and microsystems can spark a new age in the field of medicine.