Strain-Isolated Kirigami-Structured Bioelectronics for Drug Efficacy Assessment of Bulbar Muscle Functions

Introduction: : Kirigami structures, inspired by the traditional art of paper cutting, have recently emerged as a powerful tool to impart extraordinary mechanical adaptability to otherwise rigid 2D substrates[1]. By introducing rationally designed cut patterns, kirigami enables enhanced stretchability, conformality, and programmable strain distribution, crucial for the next generation of wearable bioelectronic devices. In this study, we leveraged kirigami design not merely to enhance the flexibility of a wearable device, but to implement strain isolation[2], thereby minimizing mechanical disturbances at the electrode-skin interface during vigorous motion.
We applied this kirigami-based strain isolation to develop a wireless, wearable system capable of continuously monitoring muscle function related to bulbar cord degeneration in amyotrophic lateral sclerosis (ALS) animal models[3]. Small animal models, particularly rats, present challenges due to their rapid, uncontrolled movements, which often contaminate bioelectrical signal acquisition. Here, the kirigami-incised substrates not only improved conformal attachment onto the complex 3D geometry of the rat's jaw and neck but also mechanically decoupled local strains, preserving high-fidelity electromyography (EMG) recordings during natural behaviors like eating.
Through experimental validation and theoretical modeling, we demonstrated that kirigami patterning significantly reduced strain transfer to critical sensing regions. This approach establishes a versatile, scalable design strategy for motion-resilient wearable devices. Beyond its application to ALS research, where precise bulbar muscle monitoring is critical for drug screening, this kirigami-based platform highlights a broader potential for enhancing wearable biosensors that require robust signal integrity under dynamic conditions.

Materials and

Methods: : The wearable system was fabricated by integrating ultra-thin, flexible EMG electrodes onto a substrate reinforced with kirigami patterns. The electrodes, composed of gold nanomembranes, were transferred onto a non-woven polyurethane fabric coated with a biocompatible silbione adhesive. A biaxial kirigami pattern, consisting of periodic orthogonal cuts, was engineered at the peripheries of the patch to serve as a strain isolation framework.
The design parameters of the kirigami unit cell—including the side length (2L) and gap (δ)—were optimized through mechanical simulations to maximize strain decoupling while maintaining structural integrity. Finite Element Analysis (FEA) predicted a substantial reduction of effective modulus in kirigami regions compared to unperforated substrates. This mechanical heterogeneity ensured that stretching at the device ends did not propagate to the electrode area, effectively shielding the signal acquisition sites from skin movement-induced artifacts.
The wireless system incorporated a flexible circuit module, including a rechargeable battery and Bluetooth transmission chip, mounted on the rat’s back. Custom zigzag-shaped interconnects provided mechanical compliance between the electrodes and the circuit. Devices were mounted on transgenic SOD1-G93A ALS rat models, with electrode patches aligned over masseter and digastric muscles to monitor chewing and swallowing-related EMG signals.
EMG signals were continuously recorded during voluntary food intake sessions, and muscle activity levels were compared among healthy controls, ALS models, and drug-treated ALS groups. Weekly measurements allowed tracking of disease progression. Parallel neuromuscular junction (NMJ) histology validated the in vivo EMG trends, ensuring reliability of the wearable system for longitudinal muscle function assessment.

Results, Conclusions, and Discussions:: The kirigami-patterned wearable system exhibited distinct advantages in both mechanical design and functional performance, particularly for small animal EMG monitoring. Mechanical characterization and simulation demonstrated that incorporating a biaxial kirigami pattern at the periphery of the electrode patch significantly reduced the strain transferred to the sensing region. For example, when the device was stretched to 30% in-plane, the local strain measured at the electrode was reduced to below 5%, effectively protecting the signal interface from deformation-induced noise and maintaining stable contact during vigorous movement.
Functionally, the EMG signal-to-noise ratio (SNR) was substantially improved with kirigami-based electrodes. During chewing motions in freely moving rats, the mean SNR of the EMG signals was 23.6 ± 1.8 for the kirigami electrodes, compared to 8.7 ± 1.2 for conventional planar electrodes, representing a nearly threefold enhancement in signal clarity (p < 0.01). This improvement allowed for consistent data acquisition, with the kirigami devices maintaining signal integrity across the majority of trials, while control devices frequently failed due to slippage or motion artifacts.
The system was validated in a preclinical drug efficacy study using 21 rats divided equally into three groups: wild-type, ALS model, and ALS model treated with Edaravone. Longitudinal EMG monitoring revealed that untreated ALS rats experienced a 46.3% ± 5.4% decline in normalized EMG amplitude over five weeks, reflecting progressive neuromuscular degradation. In contrast, the Edaravone-treated group exhibited only a 21.7% ± 3.9% decrease, indicating therapeutic preservation of bulbar muscle function. These trends were corroborated by histological analysis of neuromuscular junction (NMJ) occupancy, showing a strong correlation with EMG-derived muscle activity (R² = 0.89).
In conclusion, this kirigami-integrated system enables non-invasive, high-fidelity, and longitudinal EMG monitoring in ALS animal models. By minimizing strain-induced artifacts and maintaining stable skin-electrode contact, it offers a robust platform for evaluating therapeutic efficacy in preclinical studies. The design is scalable, low-profile, and broadly applicable to wearable bioelectronics requiring conformal adhesion and motion resilience.

[1] Shyu, T., Damasceno, P., Dodd, P. et al. Nat. Mat. 2015.
[2] Rodeheaver, N. et al. Adv. Funct. Mater. 2021.
[3] Shin, B., Kwon, Y. et al. Nat. Comm. 2024.

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