Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide, underscoring the need for advanced in vitro models that closely mimic native cardiac function. Traditional models, such as single-cell cultures and 2D monolayers, fail to replicate the complex mechanoelectrical coupling of human myocardium, limiting insights into disease mechanisms and pharmacological responses. Recent advances in tissue engineering have enabled the fabrication of 3D cardiac constructs that better capture the structural and functional intricacies of the heart. Central to this progress are hydrogel scaffolds, which provide cell-adhesive, biocompatible matrices with tunable mechanics and extracellular matrix-like properties, supporting cell adhesion, proliferation, and differentiation. These constructs are increasingly integrated with biosensing platforms capable of real-time, in situ monitoring of cardiac dynamics. Innovations, such as conductive hydrogel pillars, engineered cardiac patches, and thin-film microelectrode arrays, offer high-resolution, high-throughput interrogation of electrophysiological and mechanical signals while mitigating sensor-tissue impedance mismatches. Here, we review the recent progress in hydrogel-based tissue engineering and biosensing technologies for 3D cardiac models. We highlight key advances, identify persistent challenges, and outline future directions toward synchronized mechanoelectrical monitoring. This integrated strategy offers a powerful framework for elucidating CVD pathophysiology, improving drug screening, and advancing precision cardiovascular medicine.

Investigating spontaneous membrane potentials in neurons harboring Autism Susceptibility Candidate 2 (AUTS2) defects is pivotal for elucidating the pathophysiological mechanisms of neurodevelopmental disorders and for guiding targeted therapeutic strategies. Conventional electrophysiological techniques have substantially advanced understanding of neuronal function. However, they encounter limitations in capturing transient paroxysmal depolarization shifts (PDS) in AUTS2-deficient neurons, primarily owing to ion imbalances and signal attenuation. To address these constraints, we developed a nano-needle electrode system that integrates a nano-needle electrode, a 3D surface profiling device, and a neuro-electrophysiological recording device. This minimally invasive platform enables nondestructive submicron cellular scanning, and electrophysiological recording with a signal-to-noise ratio exceeding 50 dB. Employing this system, we revealed the occurrence of PDS events and a 100-fold enhancement (surpassing 1 kHz) in neuronal firing activity with AUTS2 defects. These findings enhance the understanding of AUTS2's impact on neuronal excitability and highlight our system's potential to guide future therapies for epilepsy and neuropsychiatric disorders.

With the advancement of micro-nano fabrication technology, microbeam-based biomechanical measurement platforms have become effective tools for detecting myocardial contractility due to their high sensitivity, compact size, and ease of integration. In this paper, a piezoelectric curved micro-beam model is proposed based on the extended dielectric theory and Hamilton's principle to predict the contractile force of cardiomyocytes. The governing Eqs. and boundary conditions are derived, and the differential quadrature method (DQM) is employed for numerical solutions. The electromechanical coupling response is analyzed to indirectly measure cardiomyocyte contractility. Considering the structural complexity, adhesion patterns, and mechanical properties of cardiomyocytes, we introduce an equivalent modeling approach: ideal elastic bodies with similar physical properties are used as substitutes for real cells. Periodic thermal excitation induces thermal expansion and contraction in these bodies, thereby simulating the cyclic contraction-relaxation behavior of cardiomyocytes. This method streamlines the modeling process, improves system controllability and computational feasibility, and lays a practical foundation for subsequent experimental validation.

Crack-based strain sensors offer substantial potential for health monitoring, motion detection, and human-machine interaction. Yet their practical use is constrained by inherent performance trade-offs that make it difficult to combine high sensitivity, broad working range, and reliable linearity, as well as by the mechanical instability of brittle conductive layers. This work reports a crack sensor based on an adjustable micron-cluster structure. It is fabricated through screen printing, which enables the production of a structurally tunable carbon nanotube-polydimethylsiloxane (CNT-PDMS) composite film. By controlling the cluster density and size, we successfully guide the formation of high-density, alternating long-short channel-network crack morphology, thereby synergistically optimizing the sensor performance. A high gauge factor (GF) of 149.51 and excellent linearity (R2 = 0.979) over a strain range up to 80% were achieved by the fabricated sensor. After 100 cycles of 100% stretching and 360° twisting, the sensor exhibits less than 2% degradation in both sensitivity and linearity. Demonstrations in cardiomyocyte contractile force detection and wearable human-machine interaction confirm its strong potential for applications in biomedical monitoring and intelligent interactive systems.

Cardiovascular disease remains a leading cause of mortality worldwide, driving the need for novel platforms that capture both the electrical and mechanical facets of cardiac function. While high-resolution electrophysiological techniques, such as patch clamp and microelectrode arrays, provide detailed insights into the electrical activity of cardiomyocytes, methods to accurately resolve their mechanical contractility are still limited. Conventional heart-on-a-chip devices typically employ sensors with low bandwidth and high damping, which distort the fine-scale mechanical signals critical to understanding excitation-contraction coupling. Here, we present a novel, butterfly wing-inspired heart-on-a-chip platform that incorporates a carbon nanotube (CNT)/polymethylmethacrylate (PMMA)-based strain sensor fabricated via direct ink writing, achieving a bandwidth of 22.85 Hz. This enhanced capability enables high-fidelity, multi-frequency detection of cardiomyocyte contractile waveforms, revealing previously undetectable features such as secondary peaks and rapid strain transitions. Our approach provides a complementary tool to existing electrophysiological methods, paving the way for improved mechanistic insights and more precise drug screening in cardiovascular research.

Accurate identification of tumor boundaries is crucial for effective local treatment and protection of surrounding healthy tissue. However, current methods for rapidly characterizing local tissue biomechanical properties remain limited. In this study, we present a novel MEMS-integrated piezoelectric sensor-based medical microtool (IPS-MMT), this device can map the elastic modulus of local tissues in real time and at the sub-millimeter scale, enabling rapid and localized measurements under controlled in vitro conditions. Our device features the integration of a 100 µm‑thick piezoelectric sensor onto a 300 µm‑diameter tungsten tip fabricated via a scalable electrochemical etching platform. This configuration transduces minute tissue deformations into quantifiable electrical signals with a spatial resolution of ∼15 µm and a response time under 10 ms. In ex vivo studies on rat organs and human hepatocellular carcinoma specimens, the IPS-MMT resolved distinct tissue-stiffness differences among normal, peritumoral, and cancerous regions. Independent rheological measurements on six rat organ tissues showed a mean relative agreement of 91.83% with the IPS-MMT measurements, supporting tissue elastic modulus as a promising biomechanical biomarker for tissue differentiation and highlighting the potential of biomechanics-guided precision ablation.

Intelligent home-based rehabilitation (IHR) monitoring systems have emerged as valuable tools in postoperative joint-injury recovery, benefiting from their real-time sensing capabilities and user-friendly design. However, existing systems are commonly limited by mechanical mismatch between the sensor and human joint skin, as well as insufficient long-term self-recovery performance of sensors under high-cycle strain, which can degrade the accuracy of acquired rehabilitation data. To address these limitations, we developed an IHR monitoring system that integrates a flexible hydrogel strain sensor, a data-processing module, and a wireless communication unit. The hydrogel sensor exhibits mechanical compatibility with human skin (elastic modulus approximate to 41.96 +/- 3.44 kPa; toughness: 12.5 +/- 1.74 MJ/m3) and rapid self-recovery within 30 s. The sensor also demonstrates a high gauge factor of 11.13, without observable microcracking over 5000 cycles at 65% strain. Moreover, through the integrated strategy of these three synergistic components, the system enables remote tracking of joint rehabilitation in home-based patients. This work thus offers a viable technological pathway toward the advancement of digital and intelligent tele-rehabilitation medicine.

Mechanical stimulation can remodel the physiological mechanical microenvironment of cardiomyocytes and influence their maturation and injury progression. However, the dynamic process by which cardiomyocytes transition from adaptive maturation to injury remains unclear, because conventional endpoint assays cannot continuously track cellular states. Here, we developed a heart-on-a-chip platform that reconstructs physiological strain and fluidic microenvironments. The chip integrates traction force microscopy (TFM) and a cardiac troponin I (cTnI) biosensor, enabling synchronous monitoring of cardiomyocyte contractility and injury-associated phenotypes. Under physiological cyclic stretch (20% strain), the platform induced a mature cardiomyocyte phenotype, with the gap junction protein CX43 and cytoskeletal protein F-actin increasing by 1.22- and 2.03-fold, respectively. Through 14 days of dynamic mechano-chemical monitoring, we identified 25% strain as a critical turning point in cardiomyocyte mechanical responses. Below this threshold (5%-20%), mechanical stimulation promoted cellular maturation and enhanced contractile stress, whereas above this threshold (30%), it induced an injury-associated phenotype. This heart-on-a-chip provides a controllable and quantitative in vitro platform for optimizing mechanical stimulation windows, evaluating cardiomyocyte injury, and screening cardioprotective therapeutics.

Intracellular delivery into walled cells is essential for advancing research in plant science, microbiology, and synthetic biology. Conventional enzymatic wall degradation methods are inherently destructive, leading to poor cell survival. Micro/nanoinjection technology, which enables the physical penetration of the cell wall for direct substance introduction, has emerged as a critical solution. This review article presents a systematic overview of this technology. First, we summarize the state-of-the-art in probe design and fabrication. Next, we analyze automation and force-feedback strategies aimed at increasing operational throughput and reproducibility. We then review representative applications across various walled cell types, focusing on the mechanisms of wall penetration. Finally, we discuss technical limitations and propose a roadmap for future development, emphasizing the need for standardized protocols and integrated systems. In this review, first the key advances in probe design and fabrication strategies are summarized. Next, automation and force-feedback strategies aimed at increasing operational throughput and viability are analyzed. Then, the representative applications are discussed on penetrating the cell walls in plant and fungal cells. Finally, current achievements and technical limitations are summarized, and a road-map is proposed for future efforts.

Microplastics (MPs) are pervasive pollutants present in various environments. They have the capability to infiltrate the human gastrointestinal tract through avenues like water and food, and ultimately accumulating within the liver. However, due to the absence of reliable platforms, the transportation, uptake, and damage of microplastics in the gut-liver axis remain unclear. Here, we present the development of a gut-liver-on-a-chip (GLOC) featuring biomimetic intestinal peristalsis and a dynamic hepatic flow environment, exploring the translocation in the intestines and accumulation in the liver of MPs following oral ingestion. In comparison to conventional co-culture platforms, this chip has the capability to mimic essential physical microenvironments found within the intestines and liver (e.g., intestinal peristalsis and liver blood flow). It effectively reproduces the physiological characteristics of the intestine and liver (e.g., intestinal barrier and liver metabolism). Moreover, we infused polyethylene MPs with a diameter of 100 nm into the intestinal and hepatic chambers (concentrations ranging from 0 to 1 mg mL-1). We observed that as intestinal peristalsis increased (0%, 1%, 3%, 5%), the transport rate of MPs decreased, while the levels of oxidative stress and damage in hepatic cells decreased correspondingly. Our GLOC elucidates the process of MP transport in the intestine and uptake in the liver following oral ingestion. It underscores the critical role of intestinal peristalsis in protecting the liver from damage, and provides a novel research platform for assessing the organ-specific effects of MPs.

With the rapid development of terahertz (THz) biosensing technology, the research on trace protein detection via THz metasurfaces has attracted significant attention. Here, we propose a graphene-integrated toroidal split-ring resonator (TSRR) THz meta-sensor for detecting protein at trace levels based on the Dirac property of chemical vapor deposition (CVD) graphene. The experimental results show that the designed meta-sensor can realize the detection of midkine with a 125 pg/mL limit of detection (LOD). Furthermore, benefiting from the charge accumulation generated by the local surface plasmon resonance of gold nanoparticles (AuNPs) to induce the enhancement of the local electric field of graphene, trace carcinoembryonic antigen (CEA) detection with an LOD of 10 pg/mL is achieved assisted by CEA antibody-AuNPs. The proposed meta-sensor realizes picogram-level protein detection, providing new ideas for applying metasurface-based THz sensors in biosensing.

The effective transfer of foreign macromolecules into yeast cells has been a challenge for decades due to the tough yeast cell wall. Existing transfer methods involve cell wall removal or cell wall permeability alteration, which causes serious damage to the cell structure and affects their further budding proliferation. Traditional microinjection has been successfully applied to animal cells but is not viable for yeast cells due to the low stiffness of the glass micro-pipette tip, which is inadequate to penetrate the tough yeast cell wall. In this study, a tungsten nano-needle with an optimized tip profile was fabricated using a numerically controlled electrochemical etching platform. We successfully penetrated the tough yeast cell wall using our customized tungsten nano-needle. The experiment results confirmed the possibility of mechanically penetrating the yeast cell wall using nano-needles. This method paves a new promising way for further microinjection of foreign substances into yeast cells.

Nanoplastics (NPs) pollution threatens human health, particularly the digestive system, by exacerbating intestinal inflammation and increasing the risk of inflammatory bowel disease (IBD). Using a biomimetic gut-on-a-chip (GOC) with integrated sensors, we investigated NPs' effects and explored enhanced peristalsis as a potential intervention. The GOC mimicked intestinal peristalsis via periodic stretching and detected inflammatory cytokines IL-6 and TNF-alpha over 12 days. NPs caused cell damage, tight junction protein loss, and cytokine peaks at 24 hours. Remarkably, increasing strain from 5% to 6.5% reduced IL-6 and TNF-alpha secretion by 2.73-fold and 3.34-fold, highlighting peristalsis' protective role.

To critically evaluate the challenge and suitability of Caco-2 cells in a Gut-on-a-chip (GOC), a GOC integrated with a carcinoembryonic antigen (CEA) biosensor was developed. This three-electrode system electrochemical sensor detects CEA by antigen antibody specific binding, and it exhibits high selectivity, excellent stability, and good reproducibility. Meanwhile, CEA was discovered to be secreted front 0 to 0.22 ng/mL during the 10-day culturing of Caco-2 cells. The sustained high-level CEA secretion may induce cells to avoid apoptotic stimuli, which faithfully reflects the efficacy of a new drug and the mechanism of intestinal disease. Different kinds of cell types (e.g., intestinal primary cells, stem cell-induced differentiation) in the GOC should be attempted for drug screening in the future.

Heart-on-a-chip (HOC) platforms play a pivotal role in cardiac research, yet existing models suffer from mechanical mismatch between the soft myocardial tissue, sensors, and substrate, leading to impaired myocardial function and compromised data capture. Here, we introduce a mechanically matched HOC to address these challenges by mimicking the Young's modulus of the myocardial bilayer, including the elastic epicardium (30-70 kPa) and soft extracellular matrix (28-37 kPa). A process based on liquid-gas phase transition-induced porosification was developed, which introduces porosity into polydimethylsiloxane through controlled tetradecane phase transition, allowing for a tunable reduction in Young's modulus. This platform demonstrated excellent durability, withstanding over 1,000,000 stretch cycles, and allowed continuous electromechanical monitoring of cardiomyocyte behavior for 11 days. The mechanically matched platform promoted significant upregulation of key genes linked to cell adhesion, contraction, and electrical propagation (e.g., ITGA1, CACNA1C, SCN5A, and KCNH2) and enhanced excitation-contraction coupling by 128% compared to mismatched models. Additionally, the integration of machine learning into the HOC further improved drug classification accuracy, demonstrating the potential for advancing pharmacological evaluation.

Gut-on-chips (GoCs) serve as crucial platforms for replicating the physiological and pathological environment of the human intestine, facilitating drug screening, toxicological assessments, and disease mechanism investigations. However, current GoC designs face challenges in simultaneously replicating key physiological parameters, including Reynolds number, shear stress on the cell surface, and physiological oxygen gradients. To address this challenge, we propose an innovative biomimetic design for GoC based on the similarity principle. By establishing a proportional relationship between in vivo villus height and the protrusions formed by cell growth within GoC, we achieve geometric similarity between the chip and the intestine. Numerical simulations are employed to analyze the influence of operational parameters on critical physiological conditions. Results indicate that within an optimal flow rate range, the Re (0.197–0.25) and cell surface shear stress (0.02 dyne/cm²) in the GoC channel closely match physiological conditions. Additionally, to mitigate the high oxygen permeability of PDMS, a PVDC shielding layer is introduced to restrict oxygen diffusion, thereby stabilizing the oxygen partial pressure gradient (0.013–0.077 mol/m³) within the chip, aligning it more closely with in vivo levels. This biomimetic design strategy effectively optimizes the fluid dynamic parameters and oxygen microenvironment of GoC, enhancing their physiological relevance and offering robust support for precise intestinal function modeling and pathological research.

MiRNA-21 is a crucial biomarker involved in inflammatory pathways and is linked to gastrointestinal diseases like inflammatory bowel disease (IBD). Its dynamic expression reflects disease progression and treatment response, making it an attractive target for diagnostic and therapeutic applications. However, current in vitro models often lack the physiological relevance needed for effective biomarker monitoring, limiting their utility in drug screening and therapeutic evaluation. In this study, we developed an advanced gut-on-a-chip (GOC) platform integrated with an electrochemical biosensor to achieve high-sensitivity detection of miRNA-21. The chip replicates key aspects of the intestinal microenvironment, including dynamic medium perfusion and mechanical stretching, which support the formation of a functional intestinal barrier using Caco-2 cells. The integrated biosensor demonstrated excellent performance, with a wide linear range from 1 × 10-15 to 1 × 10-10 M, enabling precise monitoring of miRNA-21 expression. To demonstrate its utility, we established an in vitro inflammation model by introducing pro-inflammatory stimuli and monitored miRNA-21 levels dynamically. The platform successfully captured the correlation between miRNA-21 expression and inflammatory progression. Furthermore, we used the system to evaluate the effects of anti-inflammatory drugs, providing proof-of-concept for its application in drug screening.

Biomimetic gut models show promise for enhancing our understanding of intestinal disorder pathogenesis and accelerating therapeutic strategy development. Currentin vitromodels predominantly comprise traditional static cell culture and animal models. Static cell culture lacks the precise control of the complex microenvironment governing human intestinal function. Animal models provide greater microenvironment complexity but fail to accurately replicate human physiological conditions due to interspecies differences. As the available models do not accurately reflect the microphysiological environment and functions of the human intestine, their applications are limited. An optimal approach to intestinal modeling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. This review highlights biofabrication strategies for constructing biomimetic intestinal models and research approaches for simulating key intestinal physiological features. We also discuss potential biomedical applications of these models and provide an outlook on multi-scale intestinal modeling.

Developing the in vitro cardiac sensing platform is promising to study cardiac physiology, disease mechanisms, drug development, and personalized medicine. Changes in the electrophysiological activity and contractile strength of cardiomyocytes are particularly important for generating accurate in vitro cardiac platforms. Existing platforms generally have in situ sensing capabilities to capture changes in the electrophysiological or mechanical behavior of cardiomyocytes. However, sensing platforms still face challenges in high-throughput detection and simultaneous mechano-electrophysiological detection. This review covers the latest progress and shortcomings from high-throughput single physiological parameter detection platforms to mechano-electrophysiological simultaneous detection sensing platforms. Finally, we discuss the future prospects of mechano-electrophysiological sensing platforms in cardiomyocyte detection in order to achieve a more accurate and efficient in vitro cardiac sensing platform to facilitate heart disease research and drug screening.