An Ultra-Simple Charge Supplementary Strategy for High Performance Rotary Triboelectric Nanogenerators.

Free-standing rotary triboelectric nanogenerators (rTENG) can accomplish special tasks which require both high voltage and high frequency. However, the reported high performance rTENG all have complex structures for output enhancement. In this work, an ultra-simple strategy to build high performance rTENG is developed. With only one small paper strip added to the conventional structure, the output of the TENG is promoted hugely. The voltage is triplicated to 2.3 kV, and the current and charge are quintupled to 133 µA and 197 nC, respectively. The small paper strip, with the merits of ultra-simplicity, wide availability, easy accessibility and low cost, functions as a super-effective charge supplement. This simple and delicate structure enables ultra-high durability with the 2.3 kV voltage output 100% maintained after 1 000 000 cycles. This charge supplementary strategy is universally effective for many other materials, and decouples the output enhancement from any friction or contact on the metal electrodes, emphasizing a critical working principle for the rTENG. Atmospheric cold plasma is generated using the paper strip rTENG (ps-rTENG), which demonstrates strong ability to do bacteria sterilization. This simple and persistent charge supplementary strategy can be easily adopted by other designs to promote the output even further.

A responsive cascade drug delivery scaffold adapted to the therapeutic time window for peripheral nerve injury repair.

Peripheral nerve injury (PNI) is a common clinical challenge, requiring timely and orderly initiation of synergistic anti-inflammatory and reparative therapy. Although the existing cascade drug delivery system can realize sequential drug release through regulation of the chemical structure of drug carriers, it is difficult to adjust the release kinetics of each drug based on the patient's condition. Therefore, there is an urgent need to develop a cascade drug delivery system that can dynamically adjust drug release and realize personalized treatment. Herein, we developed a responsive cascade drug delivery scaffold (RCDDS) which can adapt to the therapeutic time window, in which Vitamin B12 is used in early controllable release to suppress inflammation and nerve growth factor promotes regeneration by cascade loading. The RCDDS exhibited the ability to modulate the drug release kinetics by hierarchically opening polymer chains triggered by ultrasound, enabling real-time adjustment of the anti-inflammatory and neuroregenerative therapeutic time window depending on the patient's status. In the rat sciatic nerve injury model, the RCDDS group was able to achieve neural repair effects comparable to the autograft group in terms of tissue structure and motor function recovery. The development of the RCDDS provides a useful route toward an intelligent cascade drug delivery system for personalized therapy.

Piezocatalytically-induced controllable mineralization scaffold with bone-like microenvironment to achieve endogenous bone regeneration.

Orderly hierarchical structure with balanced mechanical, chemical, and electrical properties is the basis of the natural bone microenvironment. Inspired by nature, we developed a piezocatalytically-induced controlled mineralization strategy using piezoelectric polymer poly-L-lactic acid (PLLA) fibers with ordered micro-nano structures to prepare biomimetic tissue engineering scaffolds with a bone-like microenvironment (pcm-PLLA), in which PLLA-mediated piezoelectric catalysis promoted the in-situ polymerization of dopamine and subsequently regulated the controllable growth of hydroxyapatite crystals on the fiber surface. PLLA fibers, as analogs of mineralized collagen fibers, were arranged in an oriented manner, and ultimately formed a bone-like interconnected pore structure; in addition, they also provided bone-like piezoelectric properties. The uniformly sized HA nanocrystals formed by controlled mineralization provided a bone-like mechanical strength and chemical environment. The pcm-PLLA scaffold could rapidly recruit endogenous stem cells, and promote their osteogenic differentiation by activating cell membrane calcium channels and PI3K signaling pathways through ultrasound-responsive piezoelectric signals. In addition, the scaffold also provided a suitable microenvironment to promote macrophage M2 polarization and angiogenesis, thereby enhancing bone regeneration in skull defects of rats. The proposed piezocatalytically-induced controllable mineralization strategy provides a new idea for the development of tissue engineering scaffolds that can be implemented for multimodal physical stimulation therapy.

Tumor microenviroment-responsive self-assembly of barium titanate nanoparticles with enhanced piezoelectric catalysis capabilities for efficient tumor therapy.

Catalytic therapy based on piezoelectric nanoparticles has become one of the effective strategies to eliminate tumors. However, it is still a challenge to improve the tumor delivery efficiency of piezoelectric nanoparticles, so that they can penetrate normal tissues while specifically aggregating at tumor sites and subsequently generating large amounts of reactive oxygen species (ROS) to achieve precise and efficient tumor clearance. In the present study, we successfully fabricated tumor microenvironment-responsive assembled barium titanate nanoparticles (tma-BTO NPs): in the neutral pH environment of normal tissues, tma-BTO NPs were monodisperse and possessed the ability to cross the intercellular space; whereas, the acidic environment of the tumor triggered the self-assembly of tma-BTO NPs to form submicron-scale aggregates, and deposited in the tumor microenvironment. The self-assembled tma-BTO NPs not only caused mechanical damage to tumor cells; more interestingly, they also exhibited enhanced piezoelectric catalytic efficiency and produced more ROS than monodisperse nanoparticles under ultrasonic excitation, attributed to the mutual extrusion of neighboring particles within the confined space of the assembly. tma-BTO NPs exhibited differential cytotoxicity against tumor cells and normal cells, and the stronger piezoelectric catalysis and mechanical damage induced by the assemblies resulted in significant apoptosis of mouse breast cancer cells (4T1); while there was little damage to mouse embryo osteoblast precursor cells (MC3T3-E1) under the same treatment conditions. Animal experiments confirmed that peritumoral injection of tma-BTO NPs combined with ultrasound therapy can effectively inhibit tumor progression non-invasively. The tumor microenvironment-responsive self-assembly strategy opens up new perspectives for future precise piezoelectric-catalyzed tumor therapy.

A self-powered intracardiac pacemaker in swine model.

Harvesting biomechanical energy from cardiac motion is an attractive power source for implantable bioelectronic devices. Here, we report a battery-free, transcatheter, self-powered intracardiac pacemaker based on the coupled effect of triboelectrification and electrostatic induction for the treatment of arrhythmia in large animal models. We show that the capsule-shaped device (1.75 g, 1.52 cc) can be integrated with a delivery catheter for implanting in the right ventricle of a swine through the intravenous route, which effectively converts cardiac motion energy to electricity and maintains endocardial pacing function during the three-week follow-up period. We measure in vivo open circuit voltage and short circuit current of the self-powered intracardiac pacemaker of about 6.0 V and 0.2 µA, respectively. This approach exhibits up-to-date progress in self-powered medical devices and it may overcome the inherent energy shortcomings of implantable pacemakers and other bioelectronic devices for therapy and sensing.

Bias-Free Cardiac Monitoring Capsule.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Patients often fail to recognize the early signs of CVDs, which display irregularities in cardiac contractility and may ultimately lead to heart failure. Therefore, continuously monitoring the abnormal changes in cardiac contractility may represent a novel approach to long-term CVD surveillance. Here, a zero-power consumption and implantable bias-free cardiac monitoring capsule (BCMC) is introduced based on the triboelectric effect for cardiac contractility monitoring in situ. The output performance of BCMC is improved over 10 times with nanoparticle self-adsorption method. This device can be implanted into the right ventricle of swine using catheter intervention to detect the change of cardiac contractility and the corresponding CVDs. The physiological signals can be wirelessly transmitted to a mobile terminal for analysis through the acquisition and transmission module. This work contributes to a new option for precise monitoring and early diagnosis of CVDs.

Recent progress of electroactive interface in neural engineering.

Neural tissue is an electrical responsible organ. The electricity plays a vital role in the growth and development of nerve tissue, as well as the repairing after diseases. The interface between the nervous system and external device for information transmission is called neural electroactive interface. With the development of new materials and fabrication technologies, more and more new types of neural interfaces are developed and the interfaces can play crucial roles in treating many debilitating diseases such as paralysis, blindness, deafness, epilepsy, and Parkinson's disease. Neural interfaces are developing toward flexibility, miniaturization, biocompatibility, and multifunctionality. This review presents the development of neural electrodes in terms of different materials for constructing electroactive neural interfaces, especially focus on the piezoelectric materials-based indirect neuromodulation due to their features of wireless control, excellent effect, and good biocompatibility. We discussed the challenges we need to consider before the application of these new interfaces in clinical practice. The perspectives about future directions for developing more practical electroactive interface in neural engineering are also discussed in this review. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement.

Direct Mapping of Cytomechanical Homeostasis Destruction in Osteoarthritis Based on Silicon Nanopillar Array.

Osteoarthritis (OA) is the most prevalent joint degenerative disease characterized by chronic joint inflammation. The pathogenesis of OA has not been fully elucidated yet. Cartilage erosion is the most significant pathological feature in OA, which is considered the result of cytomechanical homeostasis destruction. The cytomechanical homeostasis is maintained by the dynamic interaction between cells and the extracellular matrix, which can be reflected by cell traction force (CTF). It is critical to assess the CTF to provide a deeper understanding of the cytomechanical homeostasis destruction and progression in OA. In this study, a silicon nanopillar array (Si-NP) with high spatial resolution and aspect ratio is fabricated to investigate the CTF in response to OA. It is discovered that the CTF is degraded in OA, which is attributed to the F-actin reorganization induced by the activation of RhoA/ROCK signaling pathway. Si-NP also shows promising potential as a mechanopharmacological assessment platform for OA drug screening and evaluation.

Self-Powered Electrical Impulse Chemotherapy for Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common oral cancer of the head and neck, which causes tremendous physical and mental pain to people. Traditional chemotherapy usually results in drug resistance and side effects, affecting the therapy process. In this study, a self-powered electrical impulse chemotherapy (EIC) method based on a portable triboelectric nanogenerator (TENG) was established for OSCC therapy. A common chemotherapeutic drug, doxorubicin (DOX), was used in the experiment. The TENG designed with zigzag structure had a small size of 6 cm × 6 cm, which could controllably generate the fixed output of 200 V, 400 V and 600 V. The electrical impulses generated by the TENG increased the cell endocytosis of DOX remarkably. Besides, a simply and ingeniously designed microneedle electrode increased the intensity of electric field (EF) between two adjacent microneedle tips compared with the most used planar interdigital electrode at the same height, which was more suitable for three-dimensional (3D) cells or tissues. Based on the TENG, microneedle electrode and DOX, the self-powered EIC system demonstrated a maximal apoptotic cell ratio of 22.47% and a minimum relative 3D multicellular tumor sphere (MCTS) volume of 160% with the drug dosage of 1 µg mL-1.

Localized Myocardial Anti-Inflammatory Effects of Temperature-Sensitive Budesonide Nanoparticles during Radiofrequency Catheter Ablation.

Radiofrequency (RF) catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF), but ablation lesions will result in swelling and hematoma of local surrounding tissue, triggering inflammatory cell infiltration and increased release of inflammatory cytokines. Some studies have shown that the inflammatory response may be related to the early occurrence of AF. The most direct way to inhibit perioperative inflammation is to use anti-inflammatory drugs such as glucocorticoids. Here, we prepared polylactic-co-glycolic acid (PLGA) nanoparticles loaded with budesonide (BUD) and delivered them through irrigation of saline during the onset of ablation. Local high temperature promoted local rupture of PLGA nanoparticles, releasing BUD, and produced a timely and effective local myocardial anti-inflammatory effect, resulting in the reduction of acute hematoma and inflammatory cell infiltration and the enhancement of ablation effect. Nanoparticles would also infiltrate into the local myocardium and gradually release BUD ingredients to produce a continuous anti-inflammatory effect in the next few days. This resulted in a decrease in the level of inflammatory cytokine IL-6 and an increase of anti-inflammatory cytokine IL-10. This study explored an extraordinary drug delivery strategy to reduce ablation-related inflammation, which may prevent early recurrence of AF.

A Self-Powered Optogenetic System for Implantable Blood Glucose Control.

Diabetes treatment and rehabilitation are usually a lifetime process. Optogenetic engineered designer cell-therapy holds great promise in regulating blood glucose homeostasis. However, portable, sustainable, and long-term energy supplementation has previously presented a challenge for the use of optogenetic stimulation in vivo. Herein, we purpose a self-powered optogenetic system (SOS) for implantable blood glucose control. The SOS consists of a biocompatible far-red light (FRL) source, FRL-triggered transgene-expressing cells, a power management unit, and a flexible implantable piezoelectric nanogenerator (i-PENG) to supply long-term energy by converting biomechanical energy into electricity. Our results show that this system can harvest energy from body movement and power the FRL source, which then significantly enhanced production of a short variant of human glucagon-like peptide 1 (shGLP-1) in vitro and in vivo. Indeed, diabetic mice equipped with the SOS showed rapid restoration of blood glucose homeostasis, improved glucose, and insulin tolerance. Our results suggest that the SOS is sufficiently effective in self-powering the modulation of therapeutic outputs to control glucose homeostasis and, furthermore, present a new strategy for providing energy in optogenetic-based cell therapy.