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.
A biodegradable piezoelectric scaffold excited by exercise promotes chondrogenesis and cartilage regeneration in rabbit osteochondral defects.
The emergence of the SARS‐CoV‐2 pandemic and airborne particulate matter (PM) pollution has led to remarkably high demand for face masks. However, conventional respirators are intended for single use and made from nondegradable materials, causing serious concern for a plastic‐waste environmental crisis. Furthermore, these facemasks are weakened in humid conditions and difficult to decontaminate. Herein, a reusable, self‐sustaining, highly effective, and humidity‐resistant air filtration membrane with excellent particle‐removal efficiency is reported, based on highly controllable and stable piezoelectric electrospun poly (l‐lactic acid) (PLLA) nanofibers. The PLLA filter possesses a high filtration efficiency (>99% for PM 2.5 and >91% for PM 1.0) while providing a favorable pressure drop (≈91 Pa at normal breathing rate) for human breathing due to the piezoelectric charge naturally activated by respiration through the mask. The filter has a long, stable filtration performance and good humidity resistance, demonstrated by a minimal declination in the filtration performance of the nanofiber membrane after moisture exposure. The PLLA filter is reusable via common sterilization tools (i.e., an ultrasonic cleaning bath, autoclave, or microwave). Moreover, a prototype of a completely biodegradable PLLA nanofiber‐based facemask is fabricated and shown to decompose within 5 weeks in an accelerated degradation environment.
Immunotherapy is becoming a very common treatment for cancer, using approaches like checkpoint inhibition, T cell transfer therapy, monoclonal antibodies and cancer vaccination. However, these approaches involve high doses of immune therapeutics with problematic side effects. A promising approach to reducing the dose of immunotherapeutic agents given to a cancer patient is to combine it with electrical stimulation, which can act in two ways; it can either modulate the immune system to produce the immune cytokines and agents in the patient’s body or it can increase the cellular uptake of these immune agents via electroporation. Electrical stimulation in form of direct current has been shown to reduce tumor sizes in immune-competent mice while having no effect on tumor sizes in immune-deficient mice. Several studies have used nano-pulsed electrical stimulations to activate the immune system and drive it against tumor cells. This approach has been utilized for different types of cancers, like fibrosarcoma, hepatocellular carcinoma, human papillomavirus etc. Another common approach is to combine electrochemotherapy with immune modulation, either by inducing immunogenic cell death or injecting immunostimulants that increase the effectiveness of the treatments. Several therapies utilize electroporation to deliver immunostimulants (like genes encoded with cytokine producing sequences, cancer specific antigens or fragments of anti-tumor toxins) more effectively. Lastly, electrical stimulation of the vagus nerve can trigger production and activation of anti-tumor immune cells and immune reactions. Hence, the use of electrical stimulation to modulate the immune system in different ways can be a promising approach to treat cancer.
The necessity for multiple injections and cold‐chain storage has contributed to suboptimal vaccine utilization, especially in pandemic situations. Thermally‐stable and single‐administration vaccines hold a great potential to revolutionize the global immunization process. Here, a new approach to thermally stabilize protein‐based antigens is presented and a new high‐throughput antigen‐loading process is devised to create a single‐administration, pulsatile‐release microneedle (MN) patch which can deliver a recombinant SARS‐CoV‐2 S1‐RBD protein—a model for the COVID‐19 vaccine. Nearly 100% of the protein antigen could be stabilized at temperatures up to 100 °C for at least 1 h and at an average human body temperature (37 °C) for up to 4 months. Arrays of the stabilized S1‐RBD formulations can be loaded into the MN shells via a single‐alignment assembly step. The fabricated MNs are administered at a single time into the skin of rats and induce antibody response which could neutralize authentic SARS‐CoV‐2 viruses, providing similar immunogenic effect to that induced by multiple bolus injections of the same antigen stored in conventional cold‐chain conditions. The MN system presented herein could offer the key solution to global immunization campaigns by avoiding low patient compliance, the requirement for cold‐chain storage, and the need for multiple booster injections.
Current antibody (Ab) therapies require development of stable formulations and an optimal delivery system. Here, we present a new strategy to create a single-administration long-lasting Ab-delivery microarray (MA) patch, which can carry high doses of thermally stabilized Abs. The MA fabricated by an additive three-dimensional manufacturing technology can be fully embedded into the skin via a single application to deliver doses of Abs at multiple programmable time points, thus sustaining Ab concentrations in systemic circulation. We developed an MA formulation that stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and functionality. As an example, the b12 Ab—a broadly neutralizing Ab against HIV-1—maintained antiviral activity in vitro after MA manufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of concept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded protection against viral infections or combination HIV therapy and prevention.
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