Advanced Functional Materials

While the link between tissue organization, stimulation, and function is now acknowledged as crucial for tissue development, engineering tissues with precise, long-lasting shapes and the capability for mechanical stimulation remains challenging. This study addresses this challenge by developing a next-generation magnetic bioprinting approach to create anisotropic, shape-controlled, scaffold-free, and stretchable skeletal muscle constructs. Murine skeletal muscle cells and human induced pluripotent stem cell-derived skeletal muscle cells, labeled with iron oxide nanoparticles, were magnetically bioprinted into wrench-shaped tissues. Their magnetic properties allowed these tissues to be clipped onto magnetic needles, preserving their shape over two weeks of culture while promoting anisotropic differentiation and myoblast fusion. Additionally, the magnetic tissues could be stretched by up to 100%, enhancing their anisotropy and improving muscle maturation. This magnetic toolbox demonstrates significant advancements in muscle tissue engineering, as evidenced by enhanced indicators of myoblast differentiation, including cell fusion, increased myogenic maturation and contractility. These findings highlight the potential of magnetic-based techniques for developing advanced muscle-on-chip systems and other complex tissue constructs.

Wireless neuromodulation technologies aim to eliminate the need for invasive hardware and enhance tissue compatibility. Magnetoelectric (ME) materials enable magnetic field-induced electrical stimulation, offering a minimally invasive neural activation. However, conventional ME systems use rigid ceramic components with limited biocompatibility. Here, we report a flexible, predominantly organic ME platform composed of polyvinylidene fluoride (PVDF) nanofibers embedded with anisotropic magnetite nanodiscs (MNDs). These MNDs were selected for their unique ability to exert magnetic torque due to vortex magnetization, and their intrinsic magnetostrictive behaviour. The resulting ME fibers preserve the piezoelectric {beta}-phase of PVDF and exhibit magnetoelectric voltage coefficient of 1.26 Vcm-{superscript 1}Oe-{superscript 1}. We compare two magnetic activation strategies; torque-based and high-frequency magnetostriction, finding that magnetostriction more effectively triggers neuronal responses. In vitro calcium imaging reveals robust activation in primary cortical neurons cultured on ME fibers. Biocompatibility post-stimulation was confirmed on ex vivo human brain tissue, with no increased cell death. Implanted into the premotor cortex of freely moving mice, the fibers enabled wireless modulation of motor behaviour under an alternating magnetic field. This work presents the first demonstration of wireless magnetoelectric neuromodulation using soft, biocompatible fiber composites, paving the way for future bioelectronic interfaces free from rigid components and tethered systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=182 SRC="FIGDIR/small/660052v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@7868e7org.highwire.dtl.DTLVardef@12f32a7org.highwire.dtl.DTLVardef@1a6a7e4org.highwire.dtl.DTLVardef@5876e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

The exploration of neural circuitry is essential for understanding the computational mechanisms and physiology of the brain. Despite significant advances in materials and fabrication techniques, controlling neuronal connectivity and response in three dimensions continues to present a formidable challenge. Here, we present a method for engineering the growth of three-dimensional (3D) neural circuits with the capability for optical stimulation. We fabricated bioactive interfaces by melt electrospinning writing (MEW) of 3D printed polycaprolactone (PCL) scaffolds followed by coating with titanium carbide (Ti3C2Tx MXene). Beyond enhancing hydrophilicity, cell adhesion, and electrical conductivity, the Ti3C2Tx MXene coating enabled optocapacitance-based neuronal stimulation due to illumination-induced local temperature increases. This work presents a strategy for additive manufacturing of neural tissues with optical control for functional tissue engineering and neural circuit computation.

Neural interfacing materials must deliver exceptional electrochemical performance, while integrating safely with the central nervous system. In this study we develop PolyGraph, a flexible, conductive, and biocompatible graphene-polycaprolactone (PCL) nanocomposite designed to strike this balance, which enables fabrication of conformable multichannel microelectrode arrays. Optimised liquid-phase exfoliation produces conductive, biocompatible PVP-stabilised graphene nanosheets, which are incorporated into PCL to form flexible, processable composites - PolyGraph. This material demonstrates bio- and immuno-compatibility with sensitive primary and iPSC-derived neuronal and glial cells. PolyGraph achieves low impedance ([~]1.6 {Omega} cm2 @ 1 kHz) and high charge injection capacity (11.7 mC/cm2 for a 100 ms pulse), enhanced by NaOH surface roughening and AuPd coating. Leveraging their processability, PolyGraph composites are fabricated into flexible, individually isolated microneedle electrode arrays with biomimetic soft hyaluronic acid backings. These arrays demonstrate bidirectional neural interfacing capabilities, enabling both the delivery of controlled stimulation pulses in physiological buffer and high-resolution neuronal recording in murine brain slices, with machine learning-based event classification. Together, these advances establish PolyGraph as an optimal material platform for next-generation brain-computer interfaces and soft bioelectronic devices. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/673516v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@9beea5org.highwire.dtl.DTLVardef@150be08org.highwire.dtl.DTLVardef@1ec24d2org.highwire.dtl.DTLVardef@658209_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical Abstract & TOC Text PolyGraph, a flexible graphene-polycaprolactone nanocomposite, unites conductivity, biocompatibility, and processability for next-generation neural interfaces. Fabricated into microneedle arrays with ultra-flexible backings, PolyGraph enables bidirectional neuronal recording and stimulation in brain tissue, advancing brain-computer interface (BCI) and soft bioelectronic applications.

Human pluripotent stem cell (hPSC)-derived electrically excitable cells provide a unique window into development, but they remain electrically immature partially due to the lack of chronic stimulation. Here, we fabricated electrospun polymer nanofibers containing light-reactive reduced graphene oxide (rGO) as part of a new classes of on-demand, electrically active biomaterials to enhance cell function. Fiber size, stiffness, and electrical conductivity varied with rGO concentration, which impacted hPSC-derived cardiomyocyte and neuron responses; with acute light stimulation, cardiomyocytes exhibited increased, synchronous calcium handling, and neurons showed more calcium peaks with higher frequency. Chronic, repetitive nanofiber light stimulation caused brain organoids to become increasingly electrically active and to activate photoreceptor pathways. This work outlines a tunable method where electrical cell functions can be titrated with rGO fibers and light stimulation, and it suggests that repetitive light stimulation may provide a novel method for retinal differentiation. HIGHLIGHTSO_LIElectrospun graphene-polymer nanofibers electrically respond to light stimulation C_LIO_LILight reactive graphene nanofibers stimulate electrically excitable cells in real-time C_LIO_LIStem cell-derived cardiomyocytes and neurons on nanofibers functionally improve C_LIO_LILight-training of brain organoids induces retinal and excitable neuron maturation C_LI

Tunable culture platforms that guide cellular organization and mechanically stimulate skeletal muscle development are still unavailable due to limitations in biocompatibility and actuation triggered without contact. This study reports the rational design and fabrication of magneto-active microfiber meshes with controlled hexagonal microstructures via melt electrowriting (MEW) of a thermoplastic/graphene/iron oxide composite. In situ deposition of iron oxide nanoparticles on oxidized graphene yielded homogeneously dispersed magnetic particles with sizes above 0.5 m and low aspect ratio, preventing cellular internalization and toxicity. With these fillers, homogeneous magnetic composites with very high magnetic filler content (up to 10 wt.%) were obtained and successfully processed in a solvent-free manner for the first time. MEW of magnetic composites enabled the skeletal muscle-inspired design of hexagonal scaffolds with tunable fiber diameter, reconfigurable modularity, and zonal distribution of magneto-active and nonactive material. Importantly, the hexagonal microstructures displayed elastic deformability under tension, mitigating the mechanical limitations due to high filler content. External magnetic fields below 300 mT were sufficient to trigger out-of-plane reversible deformation leading to effective end-to-end length decrease up to 17%. Moreover, C2C12 myoblast culture on 3D Matrigel/collagen/MEW scaffolds showed that the presence of magnetic particles in the scaffolds did not significantly affect viability after 8 days with respect to scaffolds without magnetic filler. Importantly, in vitro culture demonstrated that myoblasts underwent differentiation at similar rates regardless of the presence of magnetic filler. Overall, these innovative microfiber scaffolds were proven as a magnetically deformable platform suitable for dynamic culture of skeletal muscle with potential for in vitro disease modeling.

Mitigating adverse tissue remodeling after a heart attack or myocardial infarction (MI) is critical to prevent the development of heart failure. Among various post-MI treatment strategies, mechanical reinforcement of the infarcted region with epicardial patches has promise due to its consistent improvement of chronic cardiac function and its drug- or biologic-free nature. However, despite the variety of patch materials studied to date, the lack of a programmable platform that predictably modifies early-stage cardiac biomechanics to different degrees has prevented further optimization of this strategy. Here, we introduce the matrix-mimicking bioadhesive epicardium (MMBE), a platform that can be rationally designed to achieve a wide range of anisotropic mechanical properties to offer quantifiable mechanical reinforcement of the heart upon application. The platform synergistically combines fully programmable direct-ink-writing of extracellular matrix-inspired crimped fibers and a bioadhesive for sutureless integration to the epicardium. The MMBE platform achieves an array of matrix-mimicking mechanical properties and acute modulation of cardiac biomechanics using numerical analysis, in silico studies and experimental characterizations. Furthermore, the feasibility of the MMBE platform in an in vivo rat model of MI is demonstrated. The MMBE platform can be used to systematically identify patch design parameters that alter post-MI remodeling without introducing confounding biological variables.

Focused ultrasound neuromodulation offers a promising noninvasive strategy for precise deep-brain stimulation, yet conventional piezoelectric phased arrays rely on bulky hardware, high-voltage electronics, and complex phase control, limiting their scalability and wearable integration. Photoacoustic approaches enable wireless ultrasound generation but remain constrained by a trade-off between focusing precision, penetration depth, and robustness to optical misalignment. Here, we present a geometrically encoded passive photoacoustic patch (PPP) based on a spherical double logarithmic spiral (SDLS) array that achieves intrinsically stable and programmable acoustic focusing without electronic phase modulation. By distributing hemispherical CNT/PDMS photoacoustic emitters quasi-uniformly over an equal-path spherical surface and orienting each emitter toward a predefined focal point, the device establishes geometry-dominated wavefront convergence. Numerical simulations demonstrate that curved geometry is a prerequisite for phase-free focusing, while the nonperiodic spiral topology suppresses sidelobes and mitigates interference artifacts Compared with continuous spherical or periodic concentric arrays, the SDLS architecture exhibits substantially enhanced robustness to optical axis displacement, reducing focal tilt from > 14{degrees} to approximately 5{degrees} under 2 mm lateral misalignment. Experimental three-dimensional hydrophone mapping confirms millimeter-scale focusing at approximately 7 mm depth with a full width at half-maximum of 1.3 mm and peak pressures up to 8 MPa under safe laser exposure ([≤] 20 mJ/cm2). The focal region can be continuously tuned by adjusting illumination aperture size without altering device geometry or excitation schemes. The patch demonstrates excellent thermal and acoustic stability during prolonged operation and enables region-specific motor cortex stimulation in vivo, eliciting distinct electromyographic responses in forelimb and hindlimb muscles. By shifting ultrasound beam formation from electronic phase control to intrinsic three-dimensional geometry, this work establishes a lightweight, wire-free, and optically programmable platform for robust wearable neuromodulation and scalable bioacoustic interfaces.

Successful hematopoietic stem cell transplantation (HSCT) critically depends on efficient T cell recovery, which is limited by compromised bone marrow niches following irradiation. While various factors influence the regeneration of bone and bone marrow niches, the dynamics of this process remain elusive. Here, we explore the kinetics of de novo bone and bone marrow development under varying BMP-2 doses, host immune status, and biological sex, using a cryogel of covalently crosslinked alginate and gelatin releasing BMP-2. Bone formation was monitored by ultrasonography and microcomputed tomography (microCT) analysis, while histological analysis provided insights into the relation between mineralized tissue and bone marrow formation. Bone developed within 2-4 weeks, resulting in cortical bone around the cryogels, and a trabecular bone network with hematopoietic tissue within the cryogels. Higher BMP-2 doses significantly accelerated mineralization kinetics and doubled the resident hematopoietic stem cell population. Notably, immunocompromised status delayed niche development by two weeks and reduced hematopoietic stem cells fourfold. We also found that female mice exhibited enhanced niche formation compared to males under the identical conditions. These findings provide insights into the factors that govern the spatiotemporal regulation of bone and bone marrow niche development and establish this hybrid click cryogel system as a promising platform for improving T cell reconstitution in HSCT patients.

This study presents the first in vivo and in vitro evidence of an externally controlled, predictive, MRI-based nanotheranostic agent capable of cancer cell specific targeting and killing via irreversible electroporation (IRE) in solid tumors. The rectangular-prism-shaped magnetoelectric nanoparticle is a smart nanoparticle that produces a local electric field in response to an externally applied magnetic field. When externally activated, MENPs are preferentially attracted to the highly conductive cancer cell membranes, which occurs in cancer cells because of dysregulated ion flux across their membranes. In a pancreatic adenocarcinoma murine model, MENPs activated by external magnetic fields during magnetic resonance imaging (MRI) resulted in a mean three-fold tumor volume reduction (62.3% vs 188.7%; P < .001) from a single treatment. In a longitudinal confirmatory study, 35% of mice treated with activated MENPs achieved a durable complete response for 14 weeks after one treatment. The degree of tumor volume reduction correlated with a decrease in MRI T2* relaxation time (r = .351; P = .039) which suggests that MENPs have a potential to serve as a predictive nanotheranostic agent at time of treatment. There were no discernable toxicities associated with MENPs at any timepoint or on histopathological analysis of major organs. MENPs are a noninvasive alternative modality for the treatment of cancer. SummaryWe investigated the theranostic capabilities of magnetoelectric nanoparticles (MENPs) combined with MRI via a murine model of pancreatic adenocarcinoma. MENPs leverage the magnetoelectric effect to convert an applied magnetic field into local electric fields, which can induce irreversible electroporation of tumor cell membranes when activated by MRI. Additionally, MENPs modulate MRI relaxivity, which can be used to predict the degree of tumor ablation. Through a pilot study (n=21) and a confirmatory study (n=27), we demonstrated that, [&ge;]300 {micro}g of MRI-activated MENPs significantly reduced tumor volumes, averaging a three-fold decrease as compared to controls. Furthermore, there was a direct correlation between the reduction in tumor T2 relaxation times and tumor volume reduction, highlighting the predictive prognostic value of MENPs. Six of 17 mice in the confirmatory studys experimental arms achieved a durable complete response, showcasing the potential for durable treatment outcomes. Importantly, the administration of MENPs was not associated with any evident toxicities. This study presents the first in vivo evidence of an externally controlled, MRI-based, theranostic agent that effectively targets and treats solid tumors via irreversible electroporation while sparing normal tissues, offering a new and promising approach to cancer therapy.

Electroceutical implants that deliver targeted neural stimulation have shown therapeutic potential for a wide range of neurological and peripheral disorders, yet wirelessly powering ultra-miniaturized, fully injectable systems remains a critical challenge. Here we report a Thread-like Injectable Neural TechnologY (TINY), powered via a differential tissue-coupled powering (DTCP) scheme. DTCP employs mid-frequency differential potentials applied across external electrodes on a compact, wearable transmitter to deliver energy through tissue to an ultra-miniaturized, thread-like implant that integrates a custom ASIC and PEDOT-coated receiver and stimulation electrodes. Benchtop experiments in agar phantoms characterize the power-transfer efficiency (PTE) and reveal that PTE increases with implant length while maintaining strong tolerance to angular misalignment. In vivo tests in rat hindlimbs further demonstrate wireless activation of the sciatic nerve through tissue at centimeter-scale depths, confirming effective transcutaneous energy delivery for neurostimulation. A 20-day implantation study shows stable positioning of the device with minimal tissue response, indicating excellent chronic compatibility. These findings address long-standing challenges in wirelessly powering injectable electroceuticals and establish DTCP as a scalable and alignment-robust powering strategy for future minimally invasive neuromodulation therapies.

Adoptive T cell therapy provides the T cell pool needed for immediate tumor debulking, but the infused T cells generally have a narrow repertoire for antigen recognition and limited ability for long-term protection. Here, we present a biomaterial platform that enhances adoptive T cell therapy by synergistically engaging the host immune system via in-situ antigen-free vaccination. T cells alone loaded into these localized cell depots provided significantly better control of subcutaneous B16-F10 tumors than T cells delivered through direct peritumoral injection or intravenous infusion. The anti-tumor response was significantly enhanced when T cell delivery was combined with biomaterial-driven accumulation and activation of host immune cells, as this prolonged the activation state of the delivered T cells, minimized host T cell exhaustion, and enabled long-term tumor control. This integrated approach provides both immediate tumor debulking and long-term protection against solid tumors, including against tumor antigen escape.

Bone disorders and skeletal defects represent a significant clinical challenge. Tissue engineering and regenerative medicine (TERM) strategies using 3D bioprinting have emerged as promising alternatives, but still limited by the inability of directing stem cell differentiation in a controlled and reproducible manner. Advancing beyond this, we are proposing 3D bone printing via primed differentiation of stem cells with ultrasound (referred to here as 3DBonUS). This approach synergistically integrates low-intensity pulsed ultrasound (LIPUS) with a microfluidic-assisted 3D bioprinting platform enabling the biophysical stimulation of human bone marrow stromal cells (HBMSCs) during extrusion, promoting osteogenic differentiation without the need for post-fabrication treatments. Moreover, the incorporation of microbubbles enhanced the effects of LIPUS by amplifying mechanical signals at the cellular level. 3DBonUS was found to significantly upregulate key osteogenic markers (RUNX-2, ALP, COL1A1, BMP-2, OCN, OPN) as confirmed by immunofluorescence and RT-qPCR analysis. Furthermore, the LIPUS-treated constructs showed a significant increase in alkaline phosphatase activity and calcium deposition, indicating enhanced mineralisation. The 3DBonUS strategy represents a new modality in skeletal biofabrication, harnessing targeted minimally-invasive mechanical stimulation, with potential for manufacturing scalability and clinical application. Future studies will aim to validate 3DBonUS in vivo to assess the ultimate regenerative potential with enhanced osteogenic properties.

Neuromorphic computing, inspired by the structure of the brain, offers advantages in parallel processing, memory storage, and energy efficiency. However, current semiconductor-based neuromorphic chips require rare-earth materials and costly fabrication processes, whereas neural organoids need complex bioreactor maintenance. This study explores shiitake (Lentinula edodes) fungi as a robust, sustainable alternative, exploiting its adaptive electrical signaling, which is akin to neuronal spiking. We demonstrate fungal computing via mycelial networks interfaced with electrodes, showing that fungal memristors can be grown, trained, and preserved through dehydration, retaining functionality at frequencies up to 6 kHz. Notably, shiitake has exhibited radiation resistance, suggesting its viability for aerospace applications. Our findings show that fungal computers can provide scalable, eco-friendly platforms for neuromorphic tasks, bridging bioelectronics and unconventional computing.

Two-dimensional (2D) electronic materials hold immense promise for next-generation bio/neuro-electronic interfaces, but their biocompatibility has remained uncertain due to conflicting reports from studies focused on exfoliated flakes and suspensions. In this work, we present a comprehensive in vitro evaluation of electronic-grade large-area, chemical vapor deposition (CVD)-grown 2D materials - including platinum diselenide (PtSe2), platinum ditelluride (PtTe2), molybdenum disulfide (MoS2), and graphene - as substrates for mouse neural stem cell culture. Across all CVD-grown materials, the stem cells exhibited outstanding viability, with no significant differences in metabolic activity or live/apoptotic cell ratios compared to laminin-coated glass controls (p > 0.05). Importantly, these large-area 2D materials robustly supported neuronal differentiation, as evidenced by widespread {beta}III-tubulin expression. Strikingly, we found that flaky MoS2 promoted significantly greater neuronal maturation (>75% NeuN neurons) than any other substrate tested (25-50% NeuN; p < 0.05), revealing the critical influence of material format on bioactivity. While PtSe2 showed a tendency to promote glial lineage differentiation, our findings firmly establish large-area CVD-grown 2D materials as biocompatible, tunable platforms for neural interfacing, paving the way for their integration into advanced bio/neuro-electronic devices.

Electroconductive biomaterials (ECBs) replicate the natural bioelectrical environment of nerve tissue, promoting action potential propagation after injury and enhancing nerve regeneration through therapeutic electrical stimulation (ES). We present a highly electroactive Faradaic ECB with exceptional electrical conductivity and charge density, alongside low electrochemical impedance. These ECBs trigger action potentials at low stimulation voltages by regulating redox reactions through their intrinsic reversible behavior, thereby preventing electrode degradation and tissue damage. Our biohybrid scaffold consists of aligned microfibrous matrices of polypyrrole (PPy) and Bombyx mori silk fibroin (BmSF), functionalized with Antheraea assamensis silk fibroin (AaSF) rich in the cell-affinitive RGD tripeptide. Serving as an anionic dopant for PPy, AaSF significantly enhances the scaffolds electrical properties ([~]9.18 mS cm-1) and charge-transfer efficiency ([~]25.27 {Omega}). The scaffolds exhibit superior charge injection capacity at low potentials compared to conventional bioelectrodes (e.g., 0.46 mC cm-2 at 50 mV). Under pulsed ES at 50 mV cm-1, these scaffolds support remarkable neurite outgrowth of dorsal root ganglion (DRG) neurons up to 830 m (7 days). Notably, higher current densities and voltages decrease the rate of neurite outgrowth, highlighting the importance of optimizing ES parameters to effectively evoke functional action potentials without causing any neuronal damage. Biocompatibility assessments reveal that AaSF functionalization improves cellular behavior while minimizing immunomodulatory responses. Enhanced neuronal and glial differentiation is attributed to better cell communication facilitated by excellent adhesion and increased conductivity. In essence, this study provides a strategy for selecting optimal ES parameters for electrically excitable tissues using established electrochemical techniques. The fabricated biohybrid scaffolds hold significant promise as smart nerve guidance channels (NGCs) for future nerve regeneration therapies.

Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, we characterize the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications. After a pre-screen to evaluate the toxicity of these nanomaterials on immune cells, we selected ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs for further investigation. Bulk RNA-sequencing and flow cytometry analysis showcase that PLGA NPs trigger a transcriptional priming towards activation in NK and pan T cells. While PLGA NPs improved NK cells anti-tumoral functions in cytokines-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation. Altogether, we identified PLGAs NPs as suitable and promising candidates for further targeting approaches aiming to reactivate the immune system of cancer patients.

Current 4D materials typically rely on external stimuli such as heat or light to accomplish changes in shape, limiting the biocompatibility of these materials. Here, a composite bioink consisting of oxidized and methacrylated alginate (OMA), methacrylated gelatin (GelMA), and gelatin microspheres is developed to accomplish free-standing 4D bioprinting of cell-laden structures driven by an internal stimulus: cell-contractile forces (CCF). 4D changes in shape are directed by forming bilayer constructs consisting of one cell-free and one cell-laden layer. Human mesenchymal stem cells (hMSCs) are encapsulated to demonstrate the ability to simultaneously induce changes in shape and chondrogenic differentiation. Finally, the capability to pattern each layer of the printed constructs is exhibited to obtain complex geometric changes, including bending around two separate, non-parallel axes. Bioprinting of such 4D constructs mediated by CCF empowers the formation of more complex constructs, contributing to a greater degree of in vitro biomimicry of biological 4D phenomena.

CAR T cell therapy is a rapidly growing area of oncological treatments having a potential of becoming standard care for multiple indications. Coincidently, CRISPR/Cas gene-editing technology is entering next-generation CAR T cell product manufacturing with the promise of more precise and more controllable cell modification methodology. The intersection of these medical and molecular advancements creates an opportunity for completely new ways of designing engineered cells to help overcome current limitations of cell therapy. In this manuscript we present proof-of-concept data for a novel engineered feedback loop. We manufactured activation-inducible CAR T cells with the help of CRISPR-mediated targeted integration. This new type of engineered T cells expresses the CAR gene dependent on their activation status. This artifice opens new possibilities to regulate CAR T cell function both in vitro and in vivo. We believe that such a physiological control system can be a powerful addition to the currently available toolbox of next-generation CAR constructs.

The development of microelectrodes with high electrical performance is imperative, particularly for invasive interfaces such as deep brain stimulation (DBS) electrodes. MXene, a new family of 2D early transition metal carbides or nitrides, exhibits outstanding electrical properties and has been researched to improve bioelectronic interface. Through a wet spinning process, we fabricate MXene/PEDOT-PSS electrode fibers measuring 30 m in diameter, exhibiting an electrical conductivity of 2.16 {+/-} 1.46 x 10^5 S/m and notably low interfacial impedance. The excellent cathodic charge storage capacity (CSCc) and charge injection capacity (CIC) lead to their high performance in recording or stimulation. The electrode fibers are electrochemically stable, biocompatible, magnetic resonance imaging (MRI)-compatible, and demonstrate excellent performance in electromyography (EMG), electrocardiograph (ECG), cortical recording and subthalamic nuclei deep brain stimulation (STN-DBS) experiments.