Detectable, enzymatic degradation in the treatment of epilepsy silk hydrogel sensor

The flexible device (e.g., pressure and strain sensors) may be used in electronic devices and implantable skin. Although highly sensitive mechanical sensor research and development has made considerable progress, but the majority of wearable devices and electronic skin can only meet the requirements of monitoring. Durability, biocompatibility, treatment capacity, controlled drug release and can also trigger the degradation of flexible devices several challenges. Silkworm and spider silk protein produced has mechanical strength, biocompatibility and biodegradability. Silk mild processing conditions, which allows the electro-optical functions, optical or chemically active dopant (such as graphene, carbon nanotubes, laser dyes, metal and semiconductor nanoparticles and quantum dots) or a biological component (such as a drug, an enzyme, antibodies and antigen) doped into silk thereby retain their functional biological activity and a longer period. Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences Institute of Tao Tiger team published a Body-Integrated on Advanced Science, Enzyme-Triggered Degradable, Silk-Based Mechanical Sensors for Customized Health / Fitness Monitoring and In Situ Treatment, the authors report a set of conductive wire fibroin hydrogel (CSFH) stretching the flexible sensor, which is used wearable or implanted in the body. Doped carbon nanotubes (of CNTs) having a CSFH good flexibility, its elastic modulus of 0.001-0.15 MPa, up to 100% higher tensile properties, and have excellent rigidity and elasticity. Since the response CSFH various simple and complex movements (e.g., separate compression, stretching and bending) or various combinations thereof, so that it can be used to sense pressure and strain state, and discriminating between different behaviors. The authors show the capabilities of these devices in sign language interpreting and monitoring of physiological signals (such as during intracranial pressure (ICP) and the articulation of speech or muscle movements) area. Further, by the light – activated enzymatic degradation mechanism demand degradable hydrogel. The hydrogel sensor can effectively monitor and in-situ treatment of epilepsy. 《Adv.Sci.》:可检测、治疗癫痫病的酶降解丝质水凝胶传感器

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1. Structure and characterization of CSFH

FIG. 1a shows the basic structure and CSFHMaterial components. Silk protein of α- helix, [beta] sheet-like, short peptides and random coil, wire backbone hydrogels are formed by covalent bonds and hydrogen bonds. Due to a hydrogel doped carbon nanotubes having conductivity. CSFH has excellent compressibility, stretchability and bendability (FIG. 1b). FIG sensing mechanism described 1c- d is the contact force between the carbon nanotubes upon application of an external force. After application of tension, the stretching direction inside the gap (FIG. 1c (ii)) is increased to reduce the conductive path, resistance is increased. The initial state, the path between the carbon nanotubes increases, resistance decreases. When external pressure is applied, the internal clearance was significantly reduced (Fig. 1c (iii)), more carbon nanotubes contact each other, the conductive paths increases, resistance decreases. Bending (FIG. 1c (iv)), CSFH received a tensile strain is generated, resulting in increased resistance. Significant fluctuations in brightness Figure 1e shows a visualization application CSFH sensors, LED lamps can be programmed at the time of mechanical movement is lit, curved or straight in CSFH. In CSFH 0.25% papain solution degradable (FIG. 1f).

《Adv.Sci.》:可检测、治疗癫痫病的酶降解丝质水凝胶传感器
Figure 1. silk protein hydrogel (CSFH) biodegradable mechanical sensor. a) carbon nanotubes doped silk fibroin hydrogel basic structure and material composition. b) CSFH under different deformation photo. c) CSFH SEM images under deformation. d is a schematic view of the sensing mechanism). e) CSFH luminance sensor may detect a finger state of the LED. f) CSFH enzymatic degradation.

2. CSFH mechanical properties and electrical properties Characterization

CSFH evaluated the mechanical properties. CSFH may be a compressive stress of at least 5 cycles (FIG. 2a), while having excellent tensile (breaking strain 100%). No matter what state the sample, the current increases linearly with voltage, and CSFH in the initial state is smaller than the resistance of the tensile and bending state, but the resistance is larger than the compressed state (FIG. 2c). CSFH having desirable ohmic characteristics, which may be described as an ideal pressure and strain sensors. Figure 2d shows that the resistance decreases with increasing pressure ratio R / R0, when the pressure is less than 500 Pa, the pressure sensor having high sensitivity but at high pressure, reduced pressure sensitivity. R / R0 value of the tensile strain increases almost linearly(Fig. 2e). The sensitivity of the device is mounted to measure the index finger joint sensor, the value of R / R0 increases as the bending angle of the increasing sensitivity of 0.0045 / degrees (FIG. 2f). Figure 2g shows a pressure sensor as CSFH immediate response and cycling stability which immediate response time in the millisecond range. FIG 2h described sensor has high durability, repeatability and stability. Fast response and cycle durability are important considerations for wearable or real-time monitoring of physiological signals implantable.

《Adv.Sci.》:可检测、治疗癫痫病的酶降解丝质水凝胶传感器
Mechanical properties and performance of the sensor of FIG. 2. CSFH of. a) CSFH compression test film. b) the tensile test CSFH film. c) CSFH deformation under different I-V curve. Resistance to d) pressure, e) a tensile strain, and f) in response to the bending angle. g) immediate response CSFH sensor. h long-term durability test) CSFH sensor.

3. CSFH enzymatic degradation of

CSFH degradable crosslinked enzyme (FIG. 3a) by a protease (e.g., papain), when mixed with papain CSFH, the secondary structure of the silk protein is destroyed, CSFH gradual degradation. Papain doped porous internal structure CSFH tissue during the degradation process becomes more disordered (FIG. 3b), the external trigger can accelerate the degradation process. Compression modulus and the tensile modulus increased degradation with time significantly reduced, indicating that papain doped CSFH more easily deformable (FIG. 3c). ΔR / R0 absolute value does not vary significantly reduced degradation (FIG. 3D); the contrary, since the partial degradation of structural disorder and the interior of the porous hydrogel matrix will be a slight increase in the elastic modulus decreased CSFH make CSFH more easily deformed, more sensitive to mechanical forces, to keep the sensor described CSFH sensor sensitivity throughout the degradation process until completely decomposed. Figure 3e shows the effect of temperature on the degradation rate CSFH pH greater than, and most suitable degraded is 50 ° C, pH = 6. OF also doped by gold particles (of AuNPs) local laser heating to accelerate the degradation rate of CSFH (FIG. 3g) use.

《Adv.Sci.》:可检测、治疗癫痫病的酶降解丝质水凝胶传感器
FIG 3. CSFH degradation / decomposition characteristics. a) a schematic view of the mechanism of the degradation of papain doped. b) papain degradation doped CSFHThe SEM images. c) CSFH compressive and tensile modulus at different degradation times. d) degradation constant pressure (500Pa), the tension (20%) and a bending angle (10 °) of the resistance response. e) degradation at different temperatures and pH / decomposition rate. f) AuNP doped CSFH schematic visible degradation trigger. g) thermal imaging process of the CSFH.

4. Application CSFH real-time monitoring of physiological signals and sign language translation

The author goes on to CSFH used in sign language translation and real-time monitoring of physiological signals. As shown in FIG. 4a, on all joints of the fingers 14 CSFH sensors were installed, the sensor according to the conversation letters, words and gestures, generates a specific signature signal flexion. FIG. 4a using signal patterns of different color mapping each sensor and gesture shows the experimental results of \”hydrogel\” word. The sensor may also detect a physiological signal in a voice or articulation, such as ICP and muscle movement. CSFH membrane is sandwiched between the two electrodes to assemble a pressure sensor, and implanted into rats with intracranial space detecting intracranial pressure (FIG. 4a). Under normal conditions, the resistance change value ([Delta] R) are fluctuating rhythm, euthanasia into linear movement, show rhythmic fluctuations in the normal state of cardiac impulses ICP and respiration. The pressure sensor can monitor intracranial pressure (FIG. 4b) during a seizure, epilepsy after induction, the value of [Delta] R PNG penicillin solution decreased, indicating intracranial pressure during the seizure. CSFH sensor may also be connected to the throat to monitor the speech during muscle movement (FIG. 4C), measured or fixed onto human knee exercise such as walking, jogging, and squat (FIG. 4d). These experiments demonstrate that the party and the potential health monitoring sensor CSFH in helping patients with language barriers to communicate.

《Adv.Sci.》:可检测、治疗癫痫病的酶降解丝质水凝胶传感器
Electronic health monitoring sensor 4. CSFH FIG. a) using CSFH gesture recognition sensor at each joint. b) intracranial pressure monitored by the pressure sensor is placed in CSFH intracranial space. c) voice recognition function CSFH sensor. d) walking, jogging and squat motion recognition.

5. CSFH for the treatment of epilepsy

In addition, the sensor further having CSFH drug release function, to carry out inspection of epilepsy selectedcertificate. CSFH used microneedle array patch and sensor combination to trigger laser heat treatment (FIG. 5a). Phenobarbital drug contained microneedle array closely adhered CSFH sensor, then the patch attached to the back of the mouse health monitoring (FIG. 5b). The patch can detect the signal if the onset of epilepsy exercise and health status. When the symptoms of epilepsy, laser heating patches trigger degradation, phenobarbital released into the body to be treated (FIG. 5c). After this 10 minutes photoinitiator drug therapy, topical patches temperature reaches 42 ° C, significantly alleviate epilepsy seizures (FIGS. 5d-e).

《Adv.Sci.》:可检测、治疗癫痫病的酶降解丝质水凝胶传感器
FIG. 5. CSFH medicated binding wire microneedles into pharmaceutical visible light triggered release patch. a) see the light triggered drug release mechanism. b) nude photos back patch. c) triggering a flowchart visible through the patch treatment. d) heating the heat patch image nude mice five minutes after the laser. e) detecting and treating epilepsy.

Conclusion

Preparation of a set of flexible, stretchable, and implantable wearable CSFH sensor that has a good adhesion, rigidity and elasticity, for human skin and internal organs have good mechanical compliance. These devices may be applied to many parts of the body, to effect movement of the physiological signal monitoring and identification. In addition, papain by combining gold nanoparticles, the light may trigger degradation CSFH. The apparatus in combination with drug microneedle array may be monitored in real time and in situ treatment of epilepsy. This provides a flexible mechanical sensing loop (i.e., \”sense and respond\”) a flexible multi-functional electronic platform, in the future may be used in soft robot, clinical treatment and rehabilitation of patients detected.

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