Softening implantable bioelectronics: Material designs, applications, and future directions.

Implantable bioelectronics, integrated directly within the body, represent a potent biomedical solution for monitoring and treating a range of medical conditions, including chronic diseases, neural disorders, and cardiac conditions, through personalized medical interventions. Nevertheless, contemporary implantable bioelectronics rely heavily on rigid materials (e.g., inorganic materials and metals), leading to inflammatory responses and tissue damage due to a mechanical mismatch with biological tissues. Recently, soft electronics with mechanical properties comparable to those of biological tissues have been introduced to alleviate fatal immune responses and improve tissue conformity. Despite their myriad advantages, substantial challenges persist in surgical handling and precise positioning due to their high compliance. To surmount these obstacles, softening implantable bioelectronics has garnered significant attention as it embraces the benefits of both rigid and soft bioelectronics. These devices are rigid for easy standalone implantation, transitioning to a soft state in vivo in response to environmental stimuli, which effectively overcomes functional/biological problems inherent in the static mechanical properties of conventional implants. This article reviews recent research and development in softening materials and designs for implantable bioelectronics. Examples featuring tissue-penetrating and conformal softening devices highlight the promising potential of these approaches in biomedical applications. A concluding section delves into current challenges and outlines future directions for softening implantable device technologies, underscoring their pivotal role in propelling the evolution of next-generation bioelectronics.

Triamcinolone acetonide alleviates benign biliary stricture by ameliorating biliary fibrosis and inflammation.

We conducted a comprehensive series of molecular biological studies aimed at unraveling the intricate mechanisms underlying the anti-fibrotic effects of triamcinolone acetonide (TA) when used in conjunction with fully covered self-expandable metal stents (FCSEMS) for the management of benign biliary strictures (BBS). To decipher the molecular mechanisms responsible for the anti-fibrotic effects of corticosteroids on gallbladder mucosa, we conducted a comprehensive analysis. This analysis included various methodologies such as immunohistochemistry, ELISA, real-time PCR, and transcriptome analysis, enabling us to examine alterations in factors related to fibrosis and inflammation at both the protein and RNA levels. Overall, our findings revealed a dose-dependent decrease in fibrosisrelated signaling with higher TA concentrations. The 15 mg of steroid treatment (1X) exhibited anti-fibrosis and anti-inflammatory effects after 4 weeks, whereas the 30 mg of steroid treatment (2X) rapidly reduced fibrosis and inflammation within 2 weeks in BBS. Transcriptomic analysis results consistently demonstrated significant downregulation of fibrosis- and inflammation-related pathways and genes in steroid-treated fibroblasts. Use of corticosteroids, specifically TA, together with FCSEMS was effective for the treatment of BBS, ameliorating fibrosis and inflammation. Our molecular biological analysis supports the potential development of steroid-eluted FCSEMS as a therapeutic option for BBS in humans resulting from various surgical procedures. [BMB Reports 2024; 57(4): 200-205].

Body-temperature softening electronic ink for additive manufacturing of transformative bioelectronics via direct writing.

Mechanically transformative electronic systems (TESs) built using gallium have emerged as an innovative class of electronics due to their ability to switch between rigid and flexible states, thus expanding the versatility of electronics. However, the challenges posed by gallium's high surface tension and low viscosity have substantially hindered manufacturability, limiting high-resolution patterning of TESs. To address this challenge, we introduce a stiffness-tunable gallium-copper composite ink capable of direct ink write printing of intricate TES circuits, offering high-resolution (~50 micrometers) patterning, high conductivity, and bidirectional soft-rigid convertibility. These features enable transformative bioelectronics with design complexity akin to traditional printed circuit boards. These TESs maintain rigidity at room temperature for easy handling but soften and conform to curvilinear tissue surfaces at body temperature, adapting to dynamic tissue deformations. The proposed ink with direct ink write printing makes TES manufacturing simple and versatile, opening possibilities in wearables, implantables, consumer electronics, and robotics.

Skin preparation-free, stretchable microneedle adhesive patches for reliable electrophysiological sensing and exoskeleton robot control.

High-fidelity and comfortable recording of electrophysiological (EP) signals with on-the-fly setup is essential for health care and human-machine interfaces (HMIs). Microneedle electrodes allow direct access to the epidermis and eliminate time-consuming skin preparation. However, existing microneedle electrodes lack elasticity and reliability required for robust skin interfacing, thereby making long-term, high-quality EP sensing challenging during body movement. Here, we introduce a stretchable microneedle adhesive patch (SNAP) providing excellent skin penetrability and a robust electromechanical skin interface for prolonged and reliable EP monitoring under varying skin conditions. Results demonstrate that the SNAP can substantially reduce skin contact impedance under skin contamination and enhance wearing comfort during motion, outperforming gel and flexible microneedle electrodes. Our wireless SNAP demonstration for exoskeleton robot control shows its potential for highly reliable HMIs, even under time-dynamic skin conditions. We envision that the SNAP will open new opportunities for wearable EP sensing and its real-world applications in HMIs.

BRCA1 mutation promotes sprouting angiogenesis in inflammatory cancer-associated fibroblast of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with inferior outcomes owing to its low treatment response and high invasiveness. Based on abundant cancer-associated fibroblasts (CAFs) and frequent mutation of breast cancer-associated 1 (BRCA1) in TNBC, the characteristics of CAFs in TNBC patients with BRCA1 mutation compared to wild-type were investigated using single-cell analysis. Intriguingly, we observed that characteristics of inflammatory CAFs (iCAFs) were enriched in patients with BRCA1 mutation compared to the wild-type. iCAFs in patients with BRCA1 mutation exhibited outgoing signals to endothelial cells (ECs) clusters, including chemokine (C-X-C motif) ligand (CXCL) and vascular endothelial growth factor (VEGF). During CXCL signaling, the atypical chemokine receptor 1 (ACKR1) mainly interacts with CXCL family members in tumor endothelial cells (TECs). ACKR1-high TECs also showed high expression levels of angiogenesis-related genes, such as ANGPT2, MMP1, and SELE, which might lead to EC migration. Furthermore, iCAFs showed VEGF signals for FLT1 and KDR in TECs, which showed high co-expression with tip cell marker genes, including ZEB1 and MAFF, involved in sprouting angiogenesis. Moreover, BRCA1 mutation patients with relatively abundant iCAFs and tip cell gene expression exhibited a limited response to neoadjuvant chemotherapy, including cisplatin and bevacizumab. Importantly, our study observed the intricate link between iCAFs-mediated angiogenesis and chemoresistance in TNBC with BRCA1 mutation.

A temperature-responsive intravenous needle that irreversibly softens on insertion.

The high stiffness of intravenous needles can cause tissue injury and increase the risk of transmission of blood-borne pathogens through accidental needlesticks. Here we describe the development and performance of an intravenous needle whose stiffness and shape depend on body temperature. The needle is sufficiently stiff for insertion into soft tissue yet becomes irreversibly flexible after insertion, adapting to the shape of the blood vessel and reducing the risk of needlestick injury on removal, as we show in vein phantoms and ex vivo porcine tissue. In mice, the needles had similar fluid-delivery performance and caused substantially less inflammation than commercial devices for intravenous access of similar size. We also show that an intravenous needle integrated with a thin-film temperature sensor can monitor core body temperature in mice and detect fluid leakage in porcine tissue ex vivo. Temperature-responsive intravenous needles may improve patient care.

Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.

Conductance stable and mechanically durable bi-layer EGaIn composite-coated stretchable fiber for 1D bioelectronics.

Deformable semi-solid liquid metal particles (LMP) have emerged as a promising substitute for rigid conductive fillers due to their excellent electrical properties and stable conductance under strain. However, achieving a compact and robust coating of LMP on fibers remains a persistent challenge, mainly due to the incompatibility of conventional coating techniques with LMP. Additionally, the limited durability and absence of initial electrical conductivity of LMP restrict their widespread application. In this study, we propose a solution process that robustly and compactly assembles mechanically durable and initially conductive LMP on fibers. Specifically, we present a shearing-based deposition of polymer-attached LMP followed by additional coating with CNT-attached LMP to create bi-layer LMP composite with exceptional durability, electrical conductivity, stretchability, and biocompatibility on various fibers. The versatility and reliability of this manufacturing strategy for 1D electronics are demonstrated through the development of sewn electrical circuits, smart clothes, stretchable biointerfaced fiber, and multifunctional fiber probes.

At-home wireless sleep monitoring patches for the clinical assessment of sleep quality and sleep apnea.

Although many people suffer from sleep disorders, most are undiagnosed, leading to impairments in health. The existing polysomnography method is not easily accessible; it's costly, burdensome to patients, and requires specialized facilities and personnel. Here, we report an at-home portable system that includes wireless sleep sensors and wearable electronics with embedded machine learning. We also show its application for assessing sleep quality and detecting sleep apnea with multiple patients. Unlike the conventional system using numerous bulky sensors, the soft, all-integrated wearable platform offers natural sleep wherever the user prefers. In a clinical study, the face-mounted patches that detect brain, eye, and muscle signals show comparable performance with polysomnography. When comparing healthy controls to sleep apnea patients, the wearable system can detect obstructive sleep apnea with an accuracy of 88.5%. Furthermore, deep learning offers automated sleep scoring, demonstrating portability, and point-of-care usability. At-home wearable electronics could ensure a promising future supporting portable sleep monitoring and home healthcare.

Adolescent Parvalbumin Expression in the Left Orbitofrontal Cortex Shapes Sociability in Female Mice.

The adolescent social experience is essential for the maturation of the prefrontal cortex in mammalian species. However, it still needs to be determined which cortical circuits mature with such experience and how it shapes adult social behaviors in a sex-specific manner. Here, we examined social-approaching behaviors in male and female mice after postweaning social isolation (PWSI), which deprives social experience during adolescence. We found that the PWSI, particularly isolation during late adolescence, caused an abnormal increase in social approaches (hypersociability) only in female mice. We further found that the PWSI female mice showed reduced parvalbumin (PV) expression in the left orbitofrontal cortex (OFCL). When we measured neural activity in the female OFCL, a substantial number of neurons showed higher activity when mice sniffed other mice (social sniffing) than when they sniffed an object (object sniffing). Interestingly, the PWSI significantly reduced both the number of activated neurons and the activity level during social sniffing in female mice. Similarly, the CRISPR/Cas9-mediated knockdown of PV in the OFCL during late adolescence enhanced sociability and reduced the social sniffing-induced activity in adult female mice via decreased excitability of PV+ neurons and reduced synaptic inhibition in the OFCL Moreover, optogenetic activation of excitatory neurons or optogenetic inhibition of PV+ neurons in the OFCL enhanced sociability in female mice. Our data demonstrate that the adolescent social experience is critical for the maturation of PV+ inhibitory circuits in the OFCL; this maturation shapes female social behavior via enhancing social representation in the OFCL SIGNIFICANCE STATEMENT Adolescent social isolation often changes adult social behaviors in mammals. Yet, we do not fully understand the sex-specific effects of social isolation and the brain areas and circuits that mediate such changes. Here, we found that adolescent social isolation causes three abnormal phenotypes in female but not male mice: hypersociability, decreased PV+ neurons in the left orbitofrontal cortex (OFCL), and decreased socially evoked activity in the OFCL Moreover, parvalbumin (PV) deletion in the OFCL in vivo caused the same phenotypes in female mice by increasing excitation compared with inhibition within the OFCL Our data suggest that adolescent social experience is required for PV maturation in the OFCL, which is critical for evoking OFCL activity that shapes social behaviors in female mice.

Wireless, AI-enabled wearable thermal comfort sensor for energy-efficient, human-in-the-loop control of indoor temperature.

The conventional heating, ventilation, and air conditioning (HVAC) systems are based on a set-point control approach that only considers the temperature of the environment without reflecting the thermophysiological status of the occupant. This approach not only fails to fully satisfy individual thermal preferences, but it also makes an HVAC operation energy-inefficient. One possible solution is to control the indoor thermal condition based on an accurate prediction of the occupant's thermal comfort to prevent any unnecessary energy consumption. Here, we present an artificial intelligence (AI) wearable sensor-based human-in-the-loop HVAC control system that is operated on a real-time basis reflecting the thermophysiological condition of the occupant to automatically improve their thermal comfort while reducing the energy consumption of the building. The wristband-type, AI-based, three-point wearable temperature sensor offers excellent thermal comfort prediction accuracy (93.9%), enabling a human-centric HVAC control operation. A proof-of-concept demonstration of closed human-in-the-loop HVAC control using the AI-enabled wearable sensor system confirms both the accuracy of the thermal comfort prediction and the energy-efficiency of this approach, demonstrating its potential as a new solution that improves the occupant's thermal comfort and provides building energy savings.

Customizable, wireless and implantable neural probe design and fabrication via 3D printing.

This Protocol Extension describes the low-cost production of rapidly customizable optical neural probes for in vivo optogenetics. We detail the use of a 3D printer to fabricate minimally invasive microscale inorganic light-emitting-diode-based neural probes that can control neural circuit activity in freely behaving animals, thus extending the scope of two previously published protocols describing the fabrication and implementation of optoelectronic devices for studying intact neural systems. The 3D-printing fabrication process does not require extensive training and eliminates the need for expensive materials, specialized cleanroom facilities and time-consuming microfabrication techniques typical of conventional manufacturing processes. As a result, the design of the probes can be quickly optimized, on the basis of experimental need, reducing the cost and turnaround for customization. For example, 3D-printed probes can be customized to target multiple brain regions or scaled up for use in large animal models. This protocol comprises three procedures: (1) probe fabrication, (2) wireless module preparation and (3) implantation for in vivo assays. For experienced researchers, neural probe and wireless module fabrication requires ~2 d, while implantation should take 30-60 min per animal. Time required for behavioral assays will vary depending on the experimental design and should include at least 5 d of animal handling before implantation of the probe, to familiarize each animal to their handler, thus reducing handling stress that may influence the result of the behavioral assays. The implementation of customized probes improves the flexibility in optogenetic experimental design and increases access to wireless probes for in vivo optogenetic research.

Universal assembly of liquid metal particles in polymers enables elastic printed circuit board.

An elastic printed circuit board (E-PCB) is a conductive framework used for the facile assembly of system-level stretchable electronics. E-PCBs require elastic conductors that have high conductivity, high stretchability, tough adhesion to various components, and imperceptible resistance changes even under large strain. We present a liquid metal particle network (LMPNet) assembled by applying an acoustic field to a solid-state insulating liquid metal particle composite as the elastic conductor. The LMPNet conductor satisfies all the aforementioned requirements and enables the fabrication of a multilayered high-density E-PCB, in which numerous electronic components are intimately integrated to create highly stretchable skin electronics. Furthermore, we could generate the LMPNet in various polymer matrices, including hydrogels, self-healing elastomers, and photoresists, thus showing their potential for use in soft electronics.

Beyond Human Touch Perception: An Adaptive Robotic Skin Based on Gallium Microgranules for Pressure Sensory Augmentation.

Robotic skin with human-skin-like sensing ability holds immense potential in various fields such as robotics, prosthetics, healthcare, and industries. To catch up with human skin, numerous studies are underway on pressure sensors integrated on robotic skin to improve the sensitivity and detection range. However, due to the trade-off between them, existing pressure sensors have achieved only a single aspect, either high sensitivity or wide bandwidth. Here, an adaptive robotic skin is proposed that has both high sensitivity and broad bandwidth with an augmented pressure sensing ability beyond the human skin. A key for the adaptive robotic skin is a tunable pressure sensor built with uniform gallium microgranules embedded in an elastomer, which provides large tuning of the sensitivity and the bandwidth, excellent sensor-to-sensor uniformity, and high reliability. Through the mode conversion based on the solid-liquid phase transition of gallium microgranules, the sensor provides 97% higher sensitivity (16.97 kPa-1 ) in the soft mode and 262.5% wider bandwidth (≈1.45 MPa) in the rigid mode compared to the human skin. Successful demonstration of the adaptive robotic skin verifies its capabilities in sensing a wide spectrum of pressures ranging from subtle blood pulsation to body weight, suggesting broad use for various applications.

Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction.

Pancreatic cancer is an aggressive cancer characterized by high mortality and poor prognosis, with a survival rate of less than 5 years in advanced stages. Ivermectin, an antiparasitic drug, exerts antitumor effects in various cancer types. This is the first study to evaluate the anticancer effects of the combination of ivermectin and gemcitabine in pancreatic cancer. We found that the ivermectin-gemcitabine combination treatment suppressed pancreatic cancer more effectively than gemcitabine alone treatment. The ivermectin-gemcitabine combination inhibited cell proliferation via G1 arrest of the cell cycle, as evidenced by the downregulation of cyclin D1 expression and the mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT-3) signaling pathway. Ivermectin-gemcitabine increased cell apoptosis by inducing mitochondrial dysfunction via the overproduction of reactive oxygen species and decreased the mitochondrial membrane potential. This combination treatment also decreased the oxygen consumption rate and inhibited mitophagy, which is important for cancer cell death. Moreover, in vivo experiments confirmed that the ivermectin-gemcitabine group had significantly suppressed tumor growth compared to the gemcitabine alone group. These results indicate that ivermectin exerts synergistic effects with gemcitabine, preventing pancreatic cancer progression, and could be a potential antitumor drug for the treatment of pancreatic cancer.

Gut Epithelial Inositol Polyphosphate Multikinase Alleviates Experimental Colitis via Governing Tuft Cell Homeostasis.

BACKGROUND & AIMS: Inositol polyphosphate multikinase (IPMK), an essential enzyme for inositol phosphate metabolism, has been known to mediate major biological events such as growth. Recent studies have identified single-nucleotide polymorphisms in the IPMK gene associated with inflammatory bowel disease predisposition. Therefore, we aimed to investigate the functional significance of IPMK in gut epithelium. METHODS: We generated intestinal epithelial cell (IEC)-specific Ipmk knockout (IPMKΔIEC) mice, and assessed their vulnerability against dextran sulfate sodium-induced experimental colitis. Both bulk and single-cell RNA sequencing were performed to analyze IPMK-deficient colonic epithelial cells and colonic tuft cells. RESULTS: Although IPMKΔIEC mice developed normally and showed no intestinal abnormalities during homeostasis, Ipmk deletion aggravated dextran sulfate sodium-induced colitis, with higher clinical colitis scores, and increased epithelial barrier permeability. Surprisingly, Ipmk deletion led to a significant decrease in the number of tuft cells without influencing other IECs. Single-cell RNA sequencing of mouse colonic tuft cells showed 3 distinct populations of tuft cells, and further showed that a transcriptionally inactive population was expanded markedly in IPMKΔIEC mice, while neuronal-related cells were relatively decreased. CONCLUSIONS: Cholinergic output from tuft cells is known to be critical for the restoration of intestinal architecture upon damage, supporting that tuft cell-defective IPMKΔIEC mice are more prone to colitis. Thus, intestinal epithelial IPMK is a critical regulator of colonic integrity and tissue regeneration by determining tuft cell homeostasis and affecting cholinergic output.

Self-Cooling Gallium-Based Transformative Electronics with a Radiative Cooler for Reliable Stiffness Tuning in Outdoor Use.

Reconfigurability of a device that allows tuning of its shape and stiffness is utilized for personal electronics to provide an optimal mechanical interface for an intended purpose. Recent approaches in developing such transformative electronic systems (TES) involved the use of gallium liquid metal, which can change its liquid-solid phase by temperature to facilitate stiffness control of the device. However, the current design cannot withstand excessive heat during outdoor applications, leading to undesired softening of the device when the rigid mode of operation is favored. Here, a gallium-based TES integrated with a flexible and stretchable radiative cooler is presented, which offers zero-power thermal management for reliable rigid mode operation in the hot outdoors. The radiative cooler can both effectively reflect the heat transfer from the sun and emit thermal energy. It, therefore, allows a TES-in-the-air to maintain its temperature below the melting point of gallium (29.8 â„ƒ) under hot weather with strong sun exposure, thus preventing unwanted softening of the device. Comprehensive studies on optical, thermal, and mechanical characteristics of radiative-cooler-integrated TES, along with a proof-of-concept demonstration in the hot outdoors verify the reliability of this design approach, suggesting the possibility of expanding the use of TES in various environments.

A Personalized Electronic Tattoo for Healthcare Realized by On-the-Spot Assembly of an Intrinsically Conductive and Durable Liquid-Metal Composite.

Conventional electronic (e-) skins are a class of thin-film electronics mainly fabricated in laboratories or factories, which is incapable of rapid and simple customization for personalized healthcare. Here a new class of e-tattoos is introduced that can be directly implemented on the skin by facile one-step coating with various designs at multi-scale depending on the purpose of the user without a substrate. An e-tattoo is realized by attaching Pt-decorated carbon nanotubes on gallium-based liquid-metal particles (CMP) to impose intrinsic electrical conductivity and mechanical durability. Tuning the CMP suspension to have low-zeta potential, excellent wettability, and high-vapor pressure enables conformal and intimate assembly of particles directly on the skin in 10 s. Low-cost, ease of preparation, on-skin compatibility, and multifunctionality of CMP make it highly suitable for e-tattoos. Demonstrations of electrical muscle stimulators, photothermal patches, motion artifact-free electrophysiological sensors, and electrochemical biosensors validate the simplicity, versatility, and reliability of the e-tattoo-based approach in biomedical engineering.

Rapid meniscus-guided printing of stable semi-solid-state liquid metal microgranular-particle for soft electronics.

Liquid metal is being regarded as a promising material for soft electronics owing to its distinct combination of high electrical conductivity comparable to that of metals and exceptional deformability derived from its liquid state. However, the applicability of liquid metal is still limited due to the difficulty in simultaneously achieving its mechanical stability and initial conductivity. Furthermore, reliable and rapid patterning of stable liquid metal directly on various soft substrates at high-resolution remains a formidable challenge. In this work, meniscus-guided printing of ink containing polyelectrolyte-attached liquid metal microgranular-particle in an aqueous solvent to generate semi-solid-state liquid metal is presented. Liquid metal microgranular-particle printed in the evaporative regime is mechanically stable, initially conductive, and patternable down to 50 µm on various substrates. Demonstrations of the ultrastretchable (~500% strain) electrical circuit, customized e-skin, and zero-waste ECG sensor validate the simplicity, versatility, and reliability of this manufacturing strategy, enabling broad utility in the development of advanced soft electronics.

A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease.

Neurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, the exact role of protein aggregation in the pathophysiology of these disorders remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of protein aggregation, and the investigation of early dynamic events associated with inclusion formation. Here, we report on the development of a light-inducible protein aggregation (LIPA) system that enables spatiotemporal control of α-synuclein (α-syn) aggregation into insoluble deposits called Lewy bodies (LBs), the pathological hallmark of Parkinson disease (PD) and other proteinopathies. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical, and ultrastructural features of authentic LBs observed in PD-diseased brains. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration and PD-like motor impairments. Collectively, our findings provide a new tool for the generation, visualization, and dissection of the role of α-syn aggregation in PD.