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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.

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.

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.

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.

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.