电刺激治疗神经系统损伤疾病:研究进展与展望

神经系统损伤会扰乱神经系统内的通讯,导致基本神经功能丧失和瘫痪,这不仅给患者本人带来身体和心理上的极大伤害,严重影响患者的生活质量,还会对家庭乃至整个社会造成巨大的经济负担。自20世纪40年代的研究人员发现外源电场(EF)可以诱导神经细胞产生更多的神经突以及引导轴突定向及加速生长之后,电刺激疗法即被纳入神经损伤的治疗研究中来,并在几十年的发展中涌现出很多的优秀成果。本综述讨论了EFs对神经细胞的影响,以及应用EFs进行外周神经(PNS)和中枢神经(CNS)损伤的研究进展。在PNS中,EF能够刺激受损肢体神经的再生和功能恢复。在CNS中,可以使用EF刺激实现轴突再生并恢复患者的行走能力。另外,近年来关于一种新型的电刺激源——纳米发电机的研究进展迅速。纳米发电机是可将机械能直接转换为电能的创新能源器件。将其应用于生物医学领域,可以收集人体运动的机械能并直接输出电刺激,而不再需要外界的电能供应,这有望为电刺激治疗带来重大的创新和变革。本综述概述了近年来纳米发电机在神经系统疾病治疗方面的研究进展和应用实例。

具有骨样微环境的压电催化可控矿化支架实现内源性骨再生

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 microenvironment-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.

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 antiinflammatory 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.