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【Nat.Mater.】实现900%应变下电阻稳定,新型湿组织粘合双相生物电子突破糖尿病闭环治疗

【Nat.Mater.】实现900%应变下电阻稳定,新型湿组织粘合双相生物电子突破糖尿病闭环治疗#

文章标题: Strain-insensitive wet-tissue-adhesive biphasic bioelectronics for physicochemical monitoring and adaptive therapy

通讯作者: Wei Gao

文章链接: https://doi.org/10.1038/s41563-026-02624-4

文章概要#

引言#

植入式生物电子器件正在向集实时监测与治疗干预于一体的多功能平台迅速发展。然而,如何让植入物在高度动态且伴随形变的软组织表面保持长期、稳定的无缝集成,仍是极具挑战性的医学工程难题。传统的柔性器件在面对心脏跳动或胃肠道扩张等动态环境时,往往由于机械失配而导致信号失真、组织损伤甚至器件过早失效,且目前大多数器件仍依赖手术缝合,且缺乏实时分子级化学传感的能力。为了打破这些限制,本研究开发了一种名为 ElHyX 的新型双相平台,将物理传感、生化监测和神经调制功能完美融合,为下一代智能植入式生物电子学开辟了全新的道路。

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Fig. 1: Overview of the strain-insensitive elastomer–hydrogel biphasic multifunctional platform (ElHyX) for multimodal implantable bioelectronics.#
a, Schematic illustration of the ElHyX architecture. The elastomer phase is chemically modified with vinyl groups that participate in hydrogel polymerization, enabling seamless molecular-level integration. Conductive fillers such as EGaIn and graphite provide strain-insensitive conductivity and an electrochemically stable interface. A bioadhesive hydrogel ensures robust adhesion to wet tissue. b, Compared with conventional flexible electrodes, ElHyX eliminates the needs for sutures and enables secure, conformal integration onto soft, dynamic organs while supporting biomolecular sensing. c, Schematic of ElHyX implants applied to various organs for multimodal physiological monitoring and modulation. d, The ElHyX system can be manufactured rapidly at scale using DIW. Scale bar, 1 cm. e, Demonstrations of ElHyX adhesion and functional stability under large deformation (100% strain) and on an isolated rat heart. Scale bars, 1 cm. f, Photo of an integrated ElHyX device combining electrophysiological sensing, biomolecular monitoring and neural modulation for closed-loop disease management. Scale bar, 1 cm. g, Radar chart benchmarking ElHyX against other state-of-the-art implantable bioelectronic platforms across key materials and functionality metrics. The ElHyX system uniquely combines high stretchability, strain-insensitive performance, wet-tissue adhesion, multimodal physicochemical sensing and therapeutic feedback capabilities.#

主要实验及结论#

研究人员利用共价键合技术将引入了乙烯基侧链的改性弹性体与高度粘合的聚丙烯酸水凝胶层进行分子级一体化集成。通过在弹性体基质中嵌入共晶镓铟液态金属和石墨等功能填料,使器件表现出惊人的电学稳定性,在拉伸至900%的极高应变下电阻变化仅约15%,且在经历1000次大应变循环后无明显电阻漂移。团队利用直接墨水书写3D打印技术精准图案化构建了多功能集成器件,水凝胶层无需任何额外表面处理即可与湿润组织表面形成强韧的氢键粘合,即使在动态搏动的猪心表面也能稳固附着不脱落,展现出极佳的组织顺应性与电学信号捕获能力。

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Fig. 2: Mechanical and electromechanical characterizations of ElHyX.#

Fig. 3: Characterization of strain-insensitive ElHyX physical and chemical sensors.#
a, Schematic of ElHyX biophysical and biochemical sensors. b, Cross-sectional SEM image of ElHyX ECG electrode structure. Scale bar, 100 μm. c, SEM image of printed elastomer composites used in sensor fabrication. Scale bars, 100 μm. d, Skin–electrode impedance comparison of graphite-AESBS electrodes with and without hydrogel, and commercial gel electrodes. e,f, ElHyX bioelectrical sensor under 0% and 100% strain for ECG (e) and EMG (f) recording on human participants. g, In vitro demonstration of ElHyX-based LED array functioning on a beating porcine heart. Scale bar, 5 cm. h,i, Cyclic voltammograms (CVs) of 100 graphite-PB-SBS electrodes in 5 mM K3Fe(CN)6 (h) and statistic distribution of reduction peak current density and redox peak potential difference (i). j, Current peak densities of CVs of graphite-PB-SBS electrodes in 5 mM K3Fe(CN)6 under 0% (black) and 100% (red) strain, plotted against the square root of scan rates (_v_1/2). k, Amperometric calibration of graphite-PB electrodes with varying PB loadings in for H2O2 detection. Error bars represent the s.d. of the mean from three sensors. l, Schematic of enzymatic glucose sensor immobilized on graphite-PB-SBS electrodes and overlaid with a PU diffusion-limiting layer. CE, counter electrode; WE, working electrode; RE, reference electrode. m, Amperometric calibration of ElHyX-based glucose sensors. Error bars represent the s.d. of the mean from three sensors. Inset: linear calibration curve showing the relationship between the current response and glucose concentration. n, Strain-insensitive glucose detection under 0%, 50% and 100% strain. o, Representative live (green)/dead (red) images of HDFs seeded with and without ElHyX electrodes after 1-day, 4-day and 7-day culture. Scale bar, 100 μm. p, Quantitative analysis of metabolic activity over a 7-day culture period. Error bars represent the s.d. of the mean from three samples.#

在体外细胞实验证实器件具有优秀生物相容性的基础上,研究人员将其植入大鼠体内开展多模态应用。器件直接粘合在跳动的大鼠心脏表面,连续24小时稳定获取高保真度的常规心电图信号。同时,将集成有葡萄糖氧化酶和普鲁士蓝的传感模块植入大鼠肋骨表面,成功实现了对组织间隙液中葡萄糖浓度的动态监测与精准捕捉。更重要的是,该柔性器件可直接包裹在大鼠坐骨神经上充当无缝神经电刺激袖带,通过输送可调幅度的电流成功触发了剂量依赖性的后肢屈曲运动,证实其在体内的生化监测与神经调制双重功效。

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Fig. 4: In vivo characterization of ElHyX-based implantable electronics.#
a, Schematic illustrating the implantation of ElHyX-based ECG sensor on the surface of a rat heart. b,c, Representative ECG waveforms recorded at 0 h and 24 h post-implantation. d, Schematic of an ElHyX glucose sensor implanted on the outer surface of the rib cage of a rat to detect interstitial glucose. e,f, Real-time glucose monitoring using ElHyX electrode immediately after implantation (e) and 24 h after implantation (f). A glucose dose (0.36 g kg⁻1) was administered via retro-orbital injection at the time indicated by the arrow. g, Schematic of ElHyX electrode wrapping around the sciatic nerve for electrical stimulation and motor response. h, Quantitative analysis of leg flexion angles in response to different electrical stimulation currents, showing a dose-dependent motor response. Error bars represent the s.d. of the mean from three trials. i, Photographs of rat hindlimb flexion under stimulation currents of 0.7 mA, 0.9 mA and 1.3 mA, respectively. j,k, Histological evaluation of surrounding tissues (j) and main organs (k) via H&E staining after 28 days of implantation. Scale bars, 100 μm. l, Immunofluorescence staining of inflammatory markers in tissue surrounding the implant at day 28. Green, red and blue represent lymphocyte (CD3), macrophages (CD68) and cell nuclei, respectively. Scale bar, 50 μm.#

Fig. 5: In vivo evaluation of ElHyX-based closed-loop blood glucose regulation in diabetic rats.#
a, Schematic of the closed-loop blood glucose management concept: food intake triggers increases in blood glucose and heart rate (HR), which are sensed in real time and used to initiate VNS for insulin modulation. b,c, Schematic (b) and photograph (c) of the multifunctional ElHyX device implanted in a diabetic rat, showing the ECG sensor attached to the heart, the glucose sensor on the outer rib surface, and nerve cuff wrapped around the vagus nerve. Scale bars, 5 mm. d, In vivo monitoring of blood glucose levels and heart rate following IP glucose injection without VNS. e, In vivo evaluation of blood glucose levels and heart rate following IP glucose injection with bilateral VNS. f, In vivo demonstration of closed-loop blood glucose management after IP glucose injection with selective eVNS.#

总结及展望#

基于 ElHyX 平台的强大功能,研究团队成功在糖尿病大鼠模型中构建并验证了智能闭环血糖管理系统。该系统通过心电电极和生化传感器实时监测由摄食引起的血糖及心率上升,一旦触发双参数阈值,便会自动激活选择性迷走神经传出纤维刺激,促进胰岛素分泌并显著加速血糖恢复至正常水平。这一材料与系统层面的创新策略,使得器件功能可以通过调节墨水配方进行个性化调控,而无需改变结构设计。未来,这种高度集成化、免缝合且应变不敏感的双相平台,将在针对复杂生物环境的多模态生理监测及自主反馈式精准医疗领域发挥巨大的应用潜力。

【Nat.Mater.】实现900%应变下电阻稳定,新型湿组织粘合双相生物电子突破糖尿病闭环治疗
https://fuwari.vercel.app/posts/fluorapid/2026/07-06月/26-06045/
作者
Fluolab
发布于
2026-06-14
许可协议
CC BY-NC-SA 4.0