A Mitochondrion‐Targeting Piezoelectric Nanosystem for the Treatment of Erectile Dysfunction via Autophagy Regulation
Here, the study proposes a mitochondrion-targeted piezoelectric nanosystem that can promote mitophagy and ameliorate hyperglycemia in diabetic mice through ultrasound-assisted electric current generation and long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs) release, respectively. The findings reveal that this nanosystem can be employed for the treatment of erectile dysfunction.
Abstract
Mitochondrial damage caused by external stimuli, such as high glucose levels and inflammation, results in excessive reactive oxygen species (ROS) production. Existing antioxidants can only scavenge ROS and cannot address the root cause of ROS production, namely, abnormal mitochondria. To overcome this limitation, the study develops a piezoelectric synergistic drug-loaded nanosystem (BaTCG nanosystem) that targets mitochondria. The BaTCG nanosystem is delivered to mitochondria via triphenylphosphine modification, and generates current under the stimulation of ultrasound, thereby promoting mitochondrial autophagy and restoring mitochondrial homeostasis. In a model of diabetes-related erectile dysfunction (ED), the BaTCG nanosystem, through the current induced by the piezoelectric effect, not only promoted mitophagy, thereby reducing ROS production, but also released long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs) to effectively reduce blood glucose levels and mitochondrial damage. Each component of this nanosystem functions individually as well as synergistically, thus facilitating corpus cavernosum repair and restoring erectile function. In conclusion, the findings offer a novel therapeutic strategy for diabetes-related ED and a target for the treatment of diabetes-related conditions with functionalized nanoparticles to regulate mitophagy.
Xolography for 3D Printing in Microgravity
Xolography can 3D print versatile plastic and hydrogel parts in microgravity and a variety of resins can be processed independent from viscosity and flow properties. Just like on Earth, complex geometries, smooth surfaces and feature resolution down to 20 µm can be achieved during 20 s microgravity phases in a parabolic flight experiment.
Abstract
Xolography is a volumetric 3D printing technique utilizing intersecting light beams within a volume of photopolymer for a spatially controlled photopolymerization. Unlike layer-based methods, Xolography creates structures continuously within a closed photopolymer vat, eliminating the prevalent need for support structures and allowing full geometrical freedom at high printing speeds. The volumetric working principle does not rely on gravity, making Xolography an outstanding technology for additive manufacturing under microgravity conditions as illustrated in a set of experiments during a parabolic flight campaign. The microgravity environment obviates the need for rheology control of resins, enabling the use of low-viscosity formulations (e.g., 11 mPa s) while maintaining the fast and precise 3D printing of acrylic polymer resins and hydrogels. Xolography's speed and reliability facilitate rapid iterations of a print task between Earth's gravity and microgravity conditions. This capability positions Xolography as an ideal tool for material research and manufacturing in space, offering significant cost and efficiency advantages over traditional methods.
Self‐Selective (220) Directional Grown Copper Current Collector Design for Cycling‐Stable Anode‐Less Lithium Metal Batteries
A self-selective, preferentially Li salt-adsorbing and inorganic interphase-catalyzing copper current collector (CuCC) design is developed by incorporating Li salt into CuCC fabrication process to self-select out its salt-philic facet growth. This self-selected Cu(220) facet-dominant CuCC exhibits high selectivity and catalyzation ability for Li salt adsorption, decomposition, and inorganic interphase formation over other facets, reducing the electrode degradation speed by 33–42%.
Abstract
Anode-less lithium metal batteries (ALLMB) are promising candidates for energy storage applications owing to high-energy-density and safety characteristics. However, the unstable solid electrolyte interphase (SEI) formed on anode copper current collector (CuCC) leads to poor reversibility of uneven lithium deposition/stripping. Though the well-known knowledge of lithium salt-derived inorganic-rich SEI (iSEI) benefiting uniform lithium deposition, how to design a lithium salt-philic CuCC with undiscovered salt-philic facet that favors lithium salt adsorption and catalyzing salt decomposition into iSEI, remains unexplored yet. Here, a self-selective and iSEI-catalyzing CuCC design is developed by using lithium salt as surface-controlling agent in CuCC electrodeposition process, self-selecting out and guiding unidirectional Cu(220) facet growth as the most salt-philic facets of CuCC. This self-selected Cu(220) facet promotes the salt adsorption and formation of salt decomposition-derived iSEI in battery, thus improving the lithium plating/stripping coulombic efficiency from 99.25% to 99.50% (stable within 400 cycles), and the capacity decay rate of ALLMB is also reduced by 42.4% within 100 cycles. Practical mass-productivity of this self-selective CuCC for 350 Wh kg−1 pouch-cell fabrication is also demonstrated, providing a new self-selective current collector design strategy for improving selectivity and catalyzation of desired chemical reaction, important for high-selectivity electrochemical reaction system construction.
Polyphenol Mediated Assembly: Tailored Nano‐Dredger Unblocks Axonal Autophagosomes Retrograde Transport Traffic Jam for Accelerated Alzheimer's Waste Clearance
Customized Nano-dredger based on the complex interaction between polyphenol Lithospermic acid B (LA) and various substances, including siRNA, lipid nanovacuoles (LIP), ε-polylysine (εPLL), achieves efficient brain-neuron targeting, enhances the operability and patency of axonal autophagosome retrograde transport and autolysosomal fusion-degradation process, thereby decreasing Alzheimer's disease (AD)-related neuronal waste burden (aberrant accumulated protein/aging organelle) and achieving neuroprotection.
Abstract
Clear-cut evidence has linked defective autophagy to Alzheimer's disease (AD). Recent studies underscore a unique hurdle in AD neuronal autophagy: impaired retrograde axonal transport of autophagosomes, potent enough to induce autophagic stress and neurodegeneration. Nonetheless, pertinent therapy is unavailable. Here, a novel combinational therapy composed of siROCK2 and lithospermic acid B (LA) is introduced, tailored to dredge blocked axonal autophagy by multi-mitigating microtubule disruption, ATP depletion, oxidative stress, and autophagy initiation impediments in AD. Leveraging the recent discovery of multi-interactions between polyphenol LA and siRNA, ε-Poly-L-lysine, and anionic lipid nanovacuoles, LA and siROCK2 are successfully co-loaded into a fresh nano-drug delivery system, LIP@PL-LA/siRC, via a ratio-flexible and straightforward fabrication process. Further modification with the TPL peptide onto LIP@PL-LA/siRC creates a brain-neuron targeted, biocompatible, and pluripotent nanomedicine, named “Nano-dredger” (T-LIP@PL-LA/siRC). Nano-dredger efficiently accelerates axonal retrograde transport and lysosomal degradation of autophagosomes, thereby facilitating the clearance of neurotoxic proteins, improving neuronal complexity, and alleviating memory defects in 3×Tg-AD transgenic mice. This study provides a fresh and flexible polyphenol/siRNA co-delivery paradigm and furnishes conceptual proof that dredging axonal autophagy represents a promising AD therapeutic avenue.
Optically Pumped and Electrically Switchable Microlaser Array Based on Elliptic Deformation and Q‐Attenuation of Organic Droplet Oscillators
Optically pumped and electrically Q-switchable minute laser oscillators are invented. The oscillator is made from a robust self-standing organic droplet that deforms into a prolate spheroid under an electric field. The deformation induces the attenuation of the quality factor, leading to a halt of the laser emission. An array of droplet lasers is also demonstrated as a prototype laser display.
Abstract
Conventional laser panel displays are developed through the mass integration of electrically pumped lasers or through the incorporation of a beam steering system with an array of optically pumped lasers. Here a novel configuration of a laser panel display consisting of a non-steered pumping beam and an array of electrically Q-switchable lasers is reported. The laser oscillator consists of a robust, self-standing, and deformable minute droplet that emits laser through Whispering-Gallery Mode resonance when optically pumped. The laser oscillation is electrically switchable during optical pumping by applying a vertical electric field to the droplet. Electromagnetic and fluid dynamics simulations reveal the deformation of the droplet into a prolate spheroid under the electric field and associated attenuation of quality factor (Q-factor), leading to the halt of the laser oscillation. A 2 × 3 array of droplets is fabricated by inkjet printing as a prototype of a laser panel display, and it successfully achieves the pixel-selective switching of the oscillation.
A New Generation of Multimilliwatt‐Class Colloidal Quantum‐Dot Lasers at Full Colors
The full-color QD lasers relevant for practical implementations are achieved. These QD lasers feature the simultaneous metrics of low threshold, long operating duration, and multimilliwatt output power under quasi-steady-state pumping. To the best of the available knowledge, the multimilliwatt output power has never been realized in QD lasers before. These results open the door to practical QD lasers.
Abstract
Colloidal quantum dots (QDs) are attractive gain materials owing to the wide range of accessible colors. However, the existing QD lasers struggle to combine technologically relevant metrics of low threshold and long operating duration with considerable output powers. Here a new class of full-color QD lasers are reported, featuring low threshold, uninterrupted operation for dozens of hours, and multimilliwatt output under quasi-steady-state pumping, by coupling the high-gain QDs with a double-clad pumping scheme. Corroborated by the comprehensive transient spectroscopy and numerical simulation, it is demonstrated that the ternary QDs with specially designed fine nanostructure enable the low gain threshold, giant gain coefficient, long gain lifetime, and excellent resistance against intense photoexcitation. Meanwhile, the double-clad QD-fiber design allows for record-long light-gain interaction, high conversion efficiency, and sustained device operation. As such, the QD lasers with multimilliwatt output powers, unobserved in QD lasers to date, have been realized. Further, the proof-of-concept application for generating vortex beams with various topological charges is demonstrated. This work represents significant progress toward practical lasers based on QDs.
A Neuronal Signal Sorting and Amplifying Nanosensor for EEG‐Concordant Imaging‐Guided Precision Epilepsy Ablation
A neuronal signal sorting and amplifying nanosensor integrates real-time, dynamically reversible potassium ion (K⁺) fluorescence imaging (FI) with high-resolution structural magnetic resonance imaging (MRI). This enables electroencephalogram-concordant imaging of hidden epileptic foci and guides minimally invasive radiofrequency ablation on mice with drug-resistant focal epilepsy, resulting in sustained seizure control and improved cognitive outcomes.
Abstract
Surgery remains an essential treatment for managing drug-resistant focal epilepsy, but its accessibility and efficacy are limited in patients without distinct structural abnormalities on magnetic resonance imaging (MRI). Potassium ion (K+), a critical marker for seizure-associated neuronal signaling, shows significant promise for designing sensors targeting hidden epileptic foci. However, existing sensors cannot cross the blood-brain barrier and lack the ability to specifically enrich and amplify K+ signals in the brain with high temporal and spatial resolution. Here, an intravenously administered neuronal signal sorting and amplifying nanosensor (NSAN) is reported that combines real-time dynamic reversible K+ fluorescence imaging with high-resolution structural MRI, enabling electroencephalogram-concordant imaging of MRI-negative epileptic foci. Guided by NSANs, minimally invasive surgery is successfully performed in both intrahippocampal kainic acid (KA) epilepsy model with foci confined to the ipsilateral hippocampus, and intraperitoneal KA model where foci are randomly distributed, resulting in sustained seizure control and cognitive improvement. These findings highlight the NSAN as a transformative tool for visualizing hidden epileptic foci, thereby broadening eligibility for minimally invasive and precision surgical intervention.
Thu 03 Apr 16:00: 2024 Novo Nordisk Prize Lectures
Abstract not available
- Speaker: Professors Sir Shankar Balasubramanian and Sir David Klenerman
- Thursday 03 April 2025, 16:00-17:30
- Venue: Dept of Chemistry, (BMS) Bristol Myers Squibb Lecture Theatre.
- Series: Chemistry Departmental-wide lectures; organiser: Balasubramanian-Admin.
Tue 11 Feb 13:10: The Economic Cost of Depression: A Mendelian Randomisation Study
Are people depressed because they’re poor, or are they poor because they’re depressed? Observational studies often struggle to untangle this relationship. In our study, we exploit a natural experiment—the random assignment of genes at birth—to estimate how depression influences economic outcomes. We find that depression significantly reduces income, largely through its effects on educational and occupational attainment, as well as employment. Additionally, our analysis of longitudinal data reveals that short-term declines in mental health also lower income, though to a considerably lesser extent. These findings suggest that early-life interventions aimed at improving mental health could yield substantial economic benefits by influencing educational and occupational trajectories.
- Speaker: Fergus McCormack, PhD Candidate, Department of Economics
- Tuesday 11 February 2025, 13:10-14:00
- Venue: Richard King room, Darwin College.
- Series: Darwin College Humanities and Social Sciences Seminars; organiser: Dr Amelia Hassoun.
Remarkable ionic thermoelectric performance of high-entropy gel thermocell near room temperature
DOI: 10.1039/D4EE04247F, PaperLijuan Yang, Jiawei Chen, Cheng-Gong Han, Yongbin Zhu, Chunxia Xie, Zhenbang Liu, Haoyu Wang, Yu Bao, Dongxue Han, Li Niu
A concept of high-entropy was introduced in ionic thermoelectric gels through multi-ions interactions. Adding multi-ions rearranged the hydration shell of redox couples, boosting reaction entropy change and resulting in a remarkable performance.
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Constructing a gradient soft-coupled SEI film using a dilute ternary electrolyte system towards high-performance zinc-ion batteries with wide temperature stability
DOI: 10.1039/D4EE05894A, PaperTiantian Wang, Yuao Wang, Peng Cui, Heshun Geng, Yusheng Wu, Fang Hu, Junhua You, Kai Zhu
The electrolyte concentration plays a pivotal role in determining the efficacy of rechargeable batteries.
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Incompatible Geometry Regulation of Nanowire Assemblies Enabled Light‐Driven Shape Morphing and Motions
A nanowire assemblies-induced geometry engineering method is reported to fabricate a photoresponsive liquid crystal actuator with mechanically incompatible geometry, exhibiting a saddle-like appearance. By regulating the off-axis director angle and strip width, the configurations of the actuators undergo sharp and periodic transitions among the rings, helicoids, and spirals, enabling the generation of multi-modal photo-driven locomotion with fast velocities and high controllability.
Abstract
Photoresponsive shape-changing materials have significant applications in miniaturized smart robotics and biomedicine powered in a remote and wireless manner. Existing light-fuelled soft materials suffer from limited continuous shape manipulation and constrained mobility and locomotive modes. One promising solution is developing a hierarchical structure design approach to integrate rapid, reversible photoactive molecular alignment and mechanically incompatible geometry in a macroscopic system. Here, a nanowire assemblies-induced geometry engineering method is reported for the fabrication of silver nanowire-incorporated nematic liquid crystalline elastomers with prominent anisotropic structures at multi-length scales and incompatible elasticity that show sharp morphological transitions among the rings, helicoids, and spirals with diverse helical configurations. The engineered composite films can realize complex light-driven motions including rotating, rolling, and jumping with the controlled directionality and magnitude that are pre-encoded in their both molecular and macroscopic configurations. Owing to the great controllability of multimodal locomotion, a spiral robot can undertake task-specific configuration to climb up complex terrains. The complete regulatory relationship among molecular orientation, shape geometry, and light-driven motions is also established. This study may open an avenue for elaborate design and precise fabrication of novel shape-morphing materials for future applications in intelligent robotic systems.
Thu 13 Mar 11:30: TBC
Abstract not available
- Speaker: Matthew Jackson, Imperial College London
- Thursday 13 March 2025, 11:30-12:30
- Venue: Open Plan Area, Institute for Energy and Environmental Flows, Madingley Rise CB3 0EZ.
- Series: Institute for Energy and Environmental Flows (IEEF); organiser: Catherine Pearson.
Thu 06 Feb 13:00: Genetic drivers of early lung cancer
Lung cancer is the leading cause of cancer deaths worldwide. As it is most frequently diagnosed at late stages, our understanding of the factors driving early disease is limited. In my study, I have developed a novel model using genetically manipulated human lung cells. This model is being used to identify the genetic changes necessary and sufficient to drive the early changes observed in lung cancer. By uncovering these critical pathways, my aim is to identify potential targets for therapeutic intervention.
- Speaker: Alice Chernaik (Medicine, University of Cambridge)
- Thursday 06 February 2025, 13:00-14:00
- Venue: Richard King room, Darwin College.
- Series: Darwin College Science Seminars; organiser: Alexander R Epstein.
Sequential Stimuli‐Response System of Eu‐MOF Isomers
QIPA-Eu-1 and QIPA-Eu-2 isomers were synthesized for the construction of sequential stimuli-response (SSR) system. Solvent-driven structural transformation of the two isomers into QIPA-Eu-3 occurred, accompanied by the solid color changes from white to yellow and emergence of new emission band centered at 495 nm. Furthermore, yellow QIPA-Eu-3 powder transformed into brown QIPA-Eu-4 powder upon light illumination.
Abstract
Multiple stimuli-responsive materials hold excellent potential for the next generation smart materials owing to their unique response to external stimuli, providing a powerful impetus for the development of intelligent optical devices. The stimuli-responsive behavior of common multiple stimuli-responsive materials are independent of each other, causing the lack of multiplicity and identification for information technology, which is easy to decode. Herein, QIPA-Eu-1 and QIPA-Eu-2 isomers were prepared from QIPA and EuCl3·6H2O in different solvent thermal conditions for building sequential stimuli-response (SSR) system. Solvent-driven structural transformations of the isomers into QIPA-Eu-3 occurred, along with color change and fluorescence emission variation ascribed to the generation of QIPA aggregates. Furthermore, QIPA-Eu-3 displayed excellent photochromic behaviors. Combining theoretical calculation with well-defined experiments to reveal the mechanism, it was found that light drove the change in the dihedral angles between the quinoline nucleus and adjacent benzene rings in QIPA aggregates. Finally, on the basis of sequential stimuli-induced stepwise responsive behavior of QIPA-Eu-1, the sequential logic gate and time-dependent fluorescence dynamic anti-counterfeiting pattern were successfully constructed. This study provided a new perspective for design and construction of SSR system, which showed promising potential in the fields of data transmission and information encryption.
Evolution and Reconstruction of Air‐Electrode Surface Composition in Reversible Protonic Ceramic Cells: Mechanisms, Impacts on Catalytic Performance, and Optimization Strategies – A Review
This review comprehensively summarizes the surface evolution and reconstruction of reversible protonic ceramic cell (R-PCC) air-electrodes. It begins by analyzing the thermodynamic and kinetic contributions to surface evolutions, followed by a summary of factors that lead to electrochemical performance degradation, emphasizing on both the negative and positive effects of water. Additionally, recent advances in enhancing electrode surface activity are presented.
Abstract
Reversible protonic ceramic cells (R-PCCs) are at the forefront of electrochemical conversion devices, capable of reversibly and efficiently converting chemical energy into electricity at intermediate temperatures (350–700 °C) with zero carbon emissions. However, slow surface catalytic reactions at the air-electrode often hinder their performance and durability. The electrode surface is not merely an extension of the bulk structure, equilibrium reconstruction can lead to significantly different crystal-plane terminations and morphologies, which are influenced by material's intrinsic properties and external reaction conditions. Understanding electrode surface evolution at elevated temperatures in water-containing, oxidative atmospheres presents significant importance. In this review, a comprehensive summary of recent processes in applying advanced characterization techniques for high-temperature electrode surfaces is provided, exploring the correlations between surface evolution and performance fluctuations by examining the structural evolution and reconstruction of various air-electrode surfaces associated with degradation and activation phenomena, offering insights into their impact on electrode performance. Furthermore, reported strategies and recent advances in enhancing the electrochemical performance of R-PCCs through engineering air-electrode surfaces is discussed. This review offers valuable insights into surface evolution in R-PCCs and is expected to guide future developments in high-temperature catalysis, solid-state ionics, and energy materials.
Anti‐Self‐Discharge Capability of Zn‐Halogen Batteries Through an Entrapment‐Adsorption‐Catalysis Strategy Built Upon Separator
The mechanisms of glass fiber (GF) and Zn─Mn atom pairs-modified glass fiber separator (named as ZnMn-NC/GF) work in zinc-halogen batteries. The Mn-N4 single-atom sites are responsible for adsorption, while the Zn─Mn atom pairs are responsible for catalysis. The polyiodide can be rapidly captured and further transformed into I- before it reaches zinc anodes through this effective ZnMn-NC modified layer.
Abstract
Aqueous Zn-halogen batteries (Zn-I2/Br2) suffer from grievous self-discharge behavior, resulting in irreversible loss of active cathode material and severe corrosion of zinc anode, which ultimately leads to rapid battery failure. Herein, an entrapment-adsorption-catalysis strategy is reported, leveraging Zn─Mn atom pairs-modified glass fiber separator (designated as ZnMn-NC/GF), to effectively mitigate the self-discharge phenomenon. The in situ Raman and UV experiments, along with theoretical calculations, confirmed the single-atom Mn sites are responsible for polyiodides adsorption, while Zn─Mn atom pairs facilitated the conversion of reaction intermediates. As a result, the utilization rate of cathode active species is enhanced through this ZnMn-NC/GF separator. The fully charged Zn-I2 battery assembled with ZnMn-NC/GF maintained a Coulombic efficiency (CE) of 90.1% after being left for 120 h, as well as a capacity retention rate of 95.3% after 30000 cycles at a current density of 5 A g−1. Additionally, the Zn-Br2 battery designed with ZnMn-NC/GF separator can withstand more serious self-discharge problems of bromine species, with an average discharge voltage platform of 1.75 V at 0.5 A g−1. The self-discharge problem of aqueous Zn-halogen batteries is significantly suppressed by this entrapment-adsorption-catalysis strategy, which can serve as a crucial reference for the advancement of high-performance aqueous Zn-halogen batteries.
Dual‐Defect Regulated G‐C3N4 for Piezoelectric Catalytic Tumor Therapy with Enhanced Efficacy
In this work, a surface photoetching strategy is employed to introduce surface nitrogen vacancies on the repaired carbon nitride, significantly improving its piezoelectric performance. This defect-engineered carbon nitride, serving as an excellent sonosensitizer, can temporally and spatially generate reactive oxygen species within tumor cells under ultrasound stimulation, thereby achieving effective piezoelectric catalytic therapy for cancer.
Abstract
Piezoelectric catalysis for tumor treatment is an emerging method for generating reactive oxygen species (ROS). However, the development and optimization of piezoelectric catalytic nanomaterials remain the major challenge. Herein, by regulating the internal and surface defects of graphene phase carbon nitride (defect-engineered g-C3N4), its piezoelectricity and sonocatalytic performance is enhanced, thus achieving efficient tumor treatment. By reducing bulk defects, the charges excited by ultrasound (US) within the defect-engineered g-C3N4 can migrate more rapidly to the material surface, thereby enhancing their participation in redox reactions. Increasing surface defects not only introduce more active sites on the surface of defect-engineered g-C3N4 but also enhance the asymmetry of the defect-engineered g-C3N4 structure, resulting in excellent piezoelectric properties. This defect-engineered g-C3N4 nanosheet can effectively generate ROS in tumor cells and induce tumor cell apoptosis under US stimulation. This work not only introduces a method to enhance the piezoelectric catalytic performance of g-C3N4 but also expands the potential application of defect-engineered piezoelectric materials to tumor treatment.
Manipulating Aggregation Kinetics toward Efficient All‐Printed Organic Solar Cells
The acceptor BTP-Cy, featuring cyclohexyl side chains, is synthesized to control molecular aggregation state in solution. Compared to molecules containing benzene and undecyl side chains, BTP-Cy-based active layer exhibits suitable solubility and molecular aggregation size, leading to an optimal liquid precursor film length and film morphology. Consequently, all-printed 23.6 cm2 BTP-Cy-based modules achieve a power conversion efficiency of 16.2%.
Abstract
The power conversion efficiencies (PCEs) of all-printed organic solar cells (OSCs) remain inferior to those of spin-coated devices, primarily due to morphological variations within the bulk heterojunction processed via diverse coating/printing techniques. Herein, cyclohexyl is introduced as outer side chains to formulate a non-fullerene acceptor, BTP-Cy, aimed at modulating the molecular aggregation in solution and subsequent film formation kinetics during printing. Investigations demonstrate that BTP-Cy molecule with cyclohexyl side chains exhibits enhanced intermolecular π-π stacking, optimal solution aggregation size, and favorable phase separation. Consequently, PB3:FTCC-Br:BTP-Cy-based OSCs achieve remarkable PCEs of 20.2% and 19.5% via spin-coating and blade-coating, respectively. Furthermore, a 23.6 cm2 module exhibits a remarkable efficiency of 16.7%. This study offers a fresh perspective on tailoring the film formation kinetics of photoactive materials during printing through molecular design, paving a novel path to enhance the efficiency of all-printed OSCs.
Myocardia‐Injected Synergistically Anti‐Apoptotic and Anti‐Inflammatory Poly(amino acid) Hydrogel Relieves Ischemia‐Reperfusion Injury
A bioactive thermo-sensitive poly(amino acid) hydrogel is demonstrated to release the therapeutic drug FTY720 in a reactive oxygen species-controlled manner and achieves a synergistic effect by inhibiting apoptosis and regulating the reperfusion inflammatory microenvironments, thereby reducing ischemia-reperfusion injury and promoting tissue repair, demonstrating significant clinical potential for the treatment of ischemia-reperfusion injury.
Abstract
Reperfusion therapy is the most effective treatment for acute myocardial infarction, but its efficacy is frequently limited by ischemia-reperfusion injury (IRI). While antioxidant and anti-inflammatory therapies have shown significant potential in alleviating IRI, these strategies have not yielded satisfactory clinical outcomes. For that, a thermo-sensitive myocardial-injectable poly(amino acid) hydrogel of methoxy poly(ethylene glycol)45-poly(L-methionine20-co-L-alanine10) (mPEG45-P(Met20-co-Ala10), PMA) loaded with FTY720 (PMA/FTY720) is developed to address IRI through synergistic anti-apoptotic and anti-inflammatory effects. Upon injection into the ischemic myocardium, the PMA aqueous solution undergoes a sol-to-gel phase transition and gradually degrades in response to reactive oxygen species (ROS), releasing FTY720 on demand. PMA acts synergistically with FTY720 to inhibit cardiomyocyte apoptosis and modulate pro-inflammatory M1 macrophage polarization toward anti-inflammatory M2 macrophages by clearing ROS, thereby mitigating the inflammatory response and promoting vascular regeneration. In a rat IRI model, PMA/FTY720 reduces the apoptotic cell ratio by 81.8%, increases vascular density by 34.0%, and enhances left ventricular ejection fraction (LVEF) by 12.8%. In a rabbit IRI model, the gel-based sustained release of FTY720 enhanced LVEF by an additional 7.2% compared to individual treatment. In summary, the engineered PMA hydrogel effectively alleviates IRI through synergistic anti-apoptosis and anti-inflammation actions, offering valuable clinical potential for treating myocardial IRI.