Bionic myocardial electronic patch capable of individually adapting to mechanical properties of myocardial soft tissue and preparation method of bionic myocardial electronic patch

Abstract

The invention provides a bionic myocardial electronic patch for personalized adaptation of mechanical properties of myocardial soft tissue and a preparation method thereof, and relates to the field of regenerative medicine. The invention provides a bionic myocardial electronic patch adapted to mechanical properties of myocardial soft tissue in a personalized manner. The bionic myocardial electronic patch comprises a telescopic flexible fiber electrode, a tissue engineering fiber scaffold deposited on the surface of the telescopic flexible fiber electrode, a gold-plated nano layer on the surface of the fiber electrode and a PDMS passivation layer. After the bionic myocardial electronic patch provided by the invention is compounded and inoculated with hydrogel of myocardial cells differentiated from human pluripotent stem cells, nondestructive monitoring and transmission of electrical stimulation are realized, and meanwhile, the mechanical property of the myocardial tissue can be adjusted and adapted by the mechanical property of the tissue engineering fiber scaffold. The bionic myocardial electronic patch provided by the invention integrates the flexible electrode and the fiber scaffold, and can meet the biomechanical properties of monitoring, stimulating and adapting to myocardium at the same time.

Description

Technical Field

[0001] This invention relates to the field of regenerative medicine, and in particular to a biomimetic electronic myocardial patch that is personalized to adapt the mechanical properties of myocardial soft tissue and its preparation method. Background Technology

[0002] Ischemic heart disease is the second leading cause of death in my country, and current treatments struggle to achieve functional regeneration of damaged myocardium. Tissue-engineered myocardial patches offer a new therapeutic direction for myocardial repair. To achieve non-invasive monitoring and precise control of the electrophysiological properties before and after patch transplantation, researchers have integrated electronic devices into tissue engineering to realize relevant functions. However, there is a significant mechanical property mismatch between existing integrated electronic devices and soft myocardial tissue, which may interfere with normal myocardial contractile function and trigger immune rejection.

[0003] While optimizing electrode structure design provides a simple and controllable method for personalized adaptation to the nonlinear mechanical characteristics of soft tissues, the signal resolution of flexible electrodes increases with decreasing electrode area when acquiring electrophysiological signals, but the electrode impedance also increases accordingly. How to balance electrode size and impedance to achieve flexible electrodes with high resolution and low impedance remains a core problem that urgently needs to be solved.

[0004] Melt-write (MEW) technology, as a novel additive manufacturing technique, can fabricate micro / nanofibers to meet the spatial resolution requirements of electrophysiological signal monitoring. By precisely controlling the fiber deposition path and optimizing the network geometry, MEW-fabricated scaffolds can effectively match the nonlinear mechanical properties of myocardial tissue. However, the specific requirements of this technology on the printing materials limit its direct application in electrode fabrication.

[0005] Conductive biomaterial coating methods offer a feasible approach, and studies have shown that gold-plated MEW fiber networks exhibit good conductivity and strain response characteristics. However, how to construct myocardial electronic patches that combine mechanical adaptability, high signal resolution, and good biocompatibility, and achieve their integrated application with tissue engineering, remains a significant technical challenge in this field. In particular, ensuring high-quality electrical signal acquisition and processing while maintaining the mechanical properties of the electrodes and myocardial tissue remains a major challenge. Summary of the Invention

[0006] In view of this, the purpose of this invention is to provide a biomimetic myocardial electronic patch that is personalized to adapt to the biomechanical properties of myocardial soft tissue and its preparation method. The biomimetic myocardial electronic patch provided by this invention integrates a flexible fiber electrode and a tissue-engineered fiber scaffold, which can adapt to the biomechanical properties of myocardium, while meeting the requirements for monitoring and regulating the electrophysiological signals of myocardial cells.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] This invention provides a biomimetic electronic myocardial patch with personalized adaptability to the mechanical properties of myocardial soft tissue, comprising a stretchable flexible fiber electrode and a tissue-engineered fiber scaffold deposited on the surface of the stretchable flexible fiber electrode. The surface of the fiber electrode is plated with a gold nanolayer and a PDMS passivation layer. The stretchable flexible fiber electrode is made of thermoplastic polyurethane (TPU); the tissue-engineered fiber scaffold is made of polycaprolactone (PCL).

[0009] Preferably, the fiber diameter of the stretchable flexible fiber electrode is 10-50 μm, and the fiber waveform is a sine wave.

[0010] Preferably, the gold plating thickness of the stretchable flexible fiber electrode is 100-500 nm; and the thickness of the PDMS passivation layer is 30-80 μm.

[0011] Preferably, the tissue-engineered fiber scaffold has a fiber diameter of 10-20 μm and 1-20 fiber layers.

[0012] Preferably, the geometry of the tissue-engineered fiber scaffold includes a sinusoidal network structure with different waveforms.

[0013] This invention provides a method for preparing a biomimetic electronic patch for myocardial soft tissue with personalized adaptability to the mechanical properties described in the above technical solution, comprising the following steps: Attached Figure Description

[0014] To more clearly illustrate the embodiments or technical solutions of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below.

[0015] Figure 1 This is a schematic diagram of the overall structure of the biomimetic electronic patch for myocardial soft tissue that is personalized to adapt to the mechanical properties of myocardial soft tissue provided by the present invention. Figure 1 1-Stretchable flexible fiber electrode; 2-Tissue engineering fiber scaffold;

[0016] Figure 2 A schematic diagram of a sinusoidal network structure with different structural parameters and waveforms for tissue engineering fiber scaffolds;

[0017] Figure 3 The stress-strain curves of the sinusoidal MEW fiber scaffold in Example 1 are shown along the long axis and short axis, respectively. Detailed Implementation

[0018] This invention provides a biomimetic electronic myocardial patch with personalized adaptability to the mechanical properties of myocardial soft tissue, comprising a stretchable flexible fiber electrode and a tissue-engineered fiber scaffold deposited on the surface of the stretchable flexible fiber electrode. The surface of the fiber electrode is plated with a gold nanolayer and a PDMS passivation layer. The stretchable flexible fiber electrode is made of thermoplastic polyurethane (TPU); the tissue-engineered fiber scaffold is made of polycaprolactone (PCL).

[0019] Figure 1 This is a schematic diagram of the overall structure of the biomimetic electronic patch for myocardial soft tissue that is personalized to adapt to the mechanical properties of myocardial soft tissue provided by the present invention. Figure 1 1-Stretchable flexible fiber electrode, 2-Tissue-engineered fiber scaffold. This invention provides a personalized, adaptive biomimetic myocardial electronic patch integrating a flexible electrode and fiber scaffold to the mechanical properties of myocardial soft tissue, which will be described in detail below.

[0020] The biomimetic myocardial electronic patch provided by this invention, which is designed to personalize the mechanical properties of myocardial soft tissue, includes a stretchable flexible fiber electrode. In this invention, the fibers of the stretchable flexible fiber electrode are preferably thermoplastic polyurethane. The fiber diameter of the stretchable flexible fiber electrode is preferably 10-50 μm, specifically 10, 20, 30, 40, or 50 μm; the fiber waveform of the stretchable flexible fiber electrode is preferably a sine wave, which can be adjusted via G-code.

[0021] In this invention, the conductive material of the stretchable flexible fiber electrode is preferably gold nanoparticles, and the insulating material is preferably PDMS. In this invention, the gold plating thickness of the stretchable flexible fiber electrode is preferably 100-500 nm, specifically 100, 200, 300, 400, or 500 nm, and the PDMS passivation layer thickness is preferably 30-80 μm, specifically 30, 50, or 80 μm.

[0022] The biomimetic myocardial electronic patch provided by this invention includes a tissue-engineered fiber scaffold deposited on the surface of a stretchable flexible fiber electrode. In this invention, the fibers of the tissue-engineered fiber scaffold are preferably polycaprolactone. In this invention, the fiber diameter of the tissue-engineered fiber scaffold is preferably 10-20 μm, specifically 10, 15, or 20 μm; the number of fiber layers of the tissue-engineered fiber scaffold is preferably 1-20, specifically 1, 3, 5, 10, 15, or 20 layers; the thickness of the fiber scaffold is the product of the fiber diameter and the number of fiber layers.

[0023] In this invention, the geometric structure of each fiber layer in the tissue-engineered fiber scaffold includes a sinusoidal network structure with different waveforms. In this invention, the geometric structure of each fiber layer in the tissue-engineered fiber scaffold is as follows: Figure 2 As shown, Figure 2The magnified view in the small image shows the structural unit of the sinusoidal network structure, where 'a' is the amplitude of the sine wave, 't' is the period of the sine wave, and 'h' and 's' are the fiber spacing. Preferably, 'a' is 100-300 μm, 't' is 200-600 μm, and 'h' and 's' are 200-800 μm respectively. Anisotropic characteristics can be imparted to the fiber scaffold by adjusting 'a', 't', 'h', and 's', with the anisotropy ratio (i.e., the ratio of the Young's modulus of the scaffold in the transverse and longitudinal directions) preferably being 1.9-3.9. In this invention, the geometric structure adjustment of the fiber scaffold is achieved through G-code. In this invention, the sinusoidal network structure has a negative Poisson's ratio, enabling it to adapt to the volume deformation of the heart; its anisotropic characteristics can be imparted by adjusting the waveform and fiber spacing.

[0024] In natural myocardial tissue, the oriented, wavy collagen fiber network in the extracellular matrix provides the tissue's mechanical strength and elasticity. This invention provides an integrated biomimetic myocardial electronic patch comprising a flexible fiber electrode and a fiber scaffold. The stretchable flexible fiber electrode has a fiber diameter (10-50 μm) that matches the size of mature cardiomyocytes (15-20 μm). The gold-plated fiber electrode with a sinusoidal structure enhances the mechanical stretchability of the fiber, accommodating mechanical deformation during cardiac pulsation. When the fiber electrode is subjected to tensile strain, it straightens, but the path and cross-sectional area of ​​the electrical signal within the fiber electrode do not change significantly, thus improving signal transmission. The tissue-engineered fiber scaffold, with a fiber diameter (10-20 μm), replicates the diameter and structure of collagen fibers in the extracellular matrix. The scaffold's geometric structural unit is designed as a sinusoidal network structure, allowing for personalized control of the myocardial patch's mechanical strength and anisotropic mechanical properties by adjusting structural parameters (amplitude, period, and spacing). This matches the nonlinear mechanical behavior of a specific heart size and shape, facilitating the integration of the myocardial patch with the host's myocardial mechanical / electrical function after transplantation.

[0025] This invention provides a method for preparing a biomimetic electronic patch for myocardial soft tissue with personalized adaptability to the mechanical properties described in the above technical solution, comprising the following steps:

[0026] TPU is MEW printed to obtain stretchable flexible fibers;

[0027] The surface of the stretchable flexible fiber is coated with a gold nanolayer and a PDMS passivation layer using a spray coating technique to obtain a stretchable flexible fiber electrode.

[0028] The PCL was MEW printed on the surface of the stretchable flexible fiber electrode to obtain the biomimetic myocardial electronic patch that is personalized to adapt the mechanical properties of myocardial soft tissue.

[0029] This invention uses MEW printing on TPU to obtain stretchable flexible fibers. In this invention, the Shore A hardness of the TPU is 85A. The MEW printing conditions for the TPU include: heating the TPU to form a TPU melt; the pumping pressure of the TPU melt is 20-40 kPa; the distance from the printhead to the receiving plate is 3-5 mm; the applied voltage is 2-4 kV; and the printing speed is 800-1400 mm / min. In this invention, the heating temperature is preferably 230-250℃; the pumping pressure of the TPU is preferably controlled by an air pump, and the flow rate of the TPU melt is controlled by controlling the pumping pressure; the inner diameter of the printhead can be 0.3 mm or other sizes, and the fiber diameter is mainly changed by adjusting process parameters.

[0030] The specific operation of this invention, which involves coating gold nanoparticles and PDMS onto the surface of a flexible wire using a spray coating technique, is as follows: a gold nanoparticle conductive layer is sprayed onto the fiber and frame using a mask; then, a PDMS solution is coated onto the electrode surface as a passivation layer.

[0031] After obtaining the stretchable flexible fiber electrode, the present invention performs MEW printing on the surface of the stretchable flexible fiber electrode to obtain the biomimetic myocardial electronic patch with personalized adaptability to the mechanical properties of myocardial soft tissue. In the present invention, the weight-average molecular weight of the PCL is preferably 650,000. In the present invention, the MEW printing conditions of the PCL include: heating the PCL to form a PCL melt, the pumping pressure of the PCL melt is 7.5-8.5 kPa, the stretchable flexible fiber electrode is placed between the printing nozzle and the receiving plate, the distance between the printing nozzle and the receiving plate is 3-4 mm, the applied voltage is 4-5 kV, and the printing speed is 200-400 mm / min. In the present invention, the heating temperature is preferably 80-90℃; the pumping pressure of the PCL is preferably controlled by an air pump, and the flow rate of the PCL melt is controlled by controlling the pumping pressure of the PCL; the inner diameter of the printing nozzle can be 0.3 mm or other sizes, and the fiber diameter is mainly changed by adjusting the process parameters.

[0032] The present invention provides an integrated gold-plated flexible electrode and a biomimetic fiber scaffold for a biomimetic myocardial electronic patch. The fiber scaffold can be designed with anisotropy to achieve personalized adaptation to myocardial mechanical strength and nonlinear mechanical behavior. At the same time, it simulates the oriented wavy collagen fiber network in the extracellular matrix of cardiomyocytes to promote the directional growth and maturation of seeded cardiomyocytes. The integrated gold-plated fiber electrode with a sinusoidal structure serves as an electrode-cell interface, which can meet the mechanical deformation generated by cardiac pulsation and realize non-destructive monitoring and regulation of the electrophysiological activity of tissue-engineered myocardium.

[0033] To further illustrate the present invention, the following detailed description, in conjunction with examples, of the biomimetic electronic myocardial patch with personalized adaptability to the mechanical properties of myocardial soft tissue and its preparation method, should not be construed as limiting the scope of protection of the present invention.

[0034] Example 1

[0035] The preparation steps for a biomimetic electronic myocardial patch with personalized adaptability to the mechanical properties of myocardial soft tissue are as follows:

[0036] Bionic electronic myocardial patch ( Figure 1 (as shown) and its preparation

[0037] This example provides a biomimetic myocardial electronic patch integrating a flexible fiber electrode and a fiber scaffold, comprising a lower layer of stretchable flexible fiber electrode 1 and an upper layer of tissue-engineered fiber scaffold 2. The stretchable flexible fiber electrode 1 has a sinusoidal morphology, and the tissue-engineered fiber scaffold 2 has a sinusoidal network structure. Figure 2 (As shown).

[0038] MEW technology was used to print a stretchable flexible fiber electrode 1. The printing process parameters were as follows: thermoplastic polyurethane (TPU, 85A) was heated and melted at a constant temperature of 250℃. The flow rate of the melt TPU was controlled by an air pump, with the pump pressure set to 30kPa. The distance between the printing nozzle and the receiving plate was 5mm. The applied voltage was 3kV, and the printing speed was 1000mm / min. A sinusoidal waveform stretchable flexible fiber electrode with a fiber diameter of 20μm was obtained.

[0039] On the surface of the fabricated fiber electrode, a gold nanolayer is deposited along a set path using a spray coating technique, and a PDMS solution is coated on the electrode surface as a passivation layer. The thickness of the gold nanolayer is 300 nm, and the thickness of the PDMS passivation layer is 50 μm, thus obtaining a stretchable flexible fiber electrode.

[0040] A stretchable flexible fiber electrode was placed between the MEW printing nozzle and the receiving plate. The tissue-engineered fiber scaffold 2 was printed using MEW technology. The printing process parameters were: molten polycaprolactone (PCL, molecular weight Mw 650,000) was heated at a constant temperature of 85℃; the flow rate of the melt PCL was controlled by an air pump. The pump pressure was set to 8 kPa, the distance between the printing nozzle and the receiving plate was 3 mm, the applied voltage was 4.7 kV, and the printing speed was 250 mm / min. This resulted in an integrated biomimetic myocardial electronic patch combining the stretchable flexible fiber electrode and the tissue-engineered fiber scaffold. The sinusoidal tissue-engineered fiber scaffold had a fiber diameter of 15 μm, a major axis amplitude of 200 μm, a period of 400 μm, a minor axis amplitude of 200 μm, a period of 200 μm, fiber spacing s and h of 400 μm, and 10 fiber layers.

[0041] Using an Instron 5944 tensile testing machine, the stress-strain curves of the tissue-engineered fiber scaffold in Example 1 along the major and minor axes were measured by uniaxial tensile testing. The results are as follows: Figure 3 As shown, the tissue-engineered fiber scaffold exhibits a J-shaped stress-strain curve similar to that of myocardial soft tissue. Fitting the elastic region of the scaffold's stress-strain curve yielded the following calculations: Young's modulus E1 in the long axis direction was 0.36 MPa, elastic strain ε1 was 19%; Young's modulus E2 in the short axis direction was 0.11 MPa, elastic strain ε2 was 63%; and the scaffold's anisotropic modulus ratio E1 / E2 was 3.27.

[0042] To further investigate the monitoring and regulation performance of the biomimetic myocardial electronic patch in this embodiment on cardiomyocytes, relevant tests are required. A hydrogel containing human pluripotent stem cell-differentiated cardiomyocytes (iPSC-CMs) was seeded onto the fabricated biomimetic myocardial electronic patch to construct a myocardial electronic patch with sensing and electrical stimulation functions. Flexible sensing electrodes were connected to a data acquisition unit and a signal amplifier to monitor the local field potential of the cardiomyocytes, and the accuracy of the acquired signal was evaluated by comparing it with the results of calcium ion fluorescence staining. Cardiomyocytes were placed at room temperature to reduce their spontaneous contractile behavior. Flexible electrical stimulation electrodes were connected to a signal generator, and electrical stimulation at different frequencies (3V, 50ms, 1, 2, or 3Hz) was applied. The cardiomyocytes were observed under a microscope to see if they re-emerged contractile behavior, and the contractile behavior of cardiomyocytes under different frequencies of electrical stimulation was recorded and analyzed.

[0043] This invention provides an integrated biomimetic myocardial electronic patch that combines a stretchable flexible fiber electrode and a tissue-engineered fiber scaffold. After inoculation with a hydrogel containing cardiomyocytes differentiated from human pluripotent stem cells, it enables non-destructive monitoring and electrical stimulation. Simultaneously, the tissue-engineered fiber scaffold is mechanically adjustable to adapt to the biomechanical properties of myocardial tissue. The biomimetic myocardial electronic patch provided by this invention can simultaneously meet the requirements of monitoring, stimulating, and adapting to the biomechanical properties of the myocardium.

[0044] The above-described embodiments are merely one specific implementation of this application, and while the descriptions are detailed and specific, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications without departing from the inventive concept, and these modifications all fall within the protection scope of this invention.

Claims

1. A biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue, comprising a stretchable flexible fiber electrode and a tissue-engineered fiber scaffold deposited on the surface of the stretchable flexible fiber electrode, wherein the surface of the fiber electrode is plated with a gold nanolayer and a PDMS passivation layer, the stretchable flexible fiber electrode material is thermoplastic polyurethane (TPU), and the tissue-engineered fiber scaffold material is polycaprolactone (PCL).

2. The biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue according to claim 1, characterized in that, The stretchable flexible fiber electrode has a fiber diameter of 10-50 μm and a sine wave waveform.

3. The biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue according to claim 1, characterized in that, The gold plating thickness of the stretchable flexible fiber electrode is 100-500 nm; the thickness of the PDMS passivation layer coating is 30-80 μm.

4. The biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue according to claim 1, characterized in that, The tissue-engineered fiber scaffold has a fiber diameter of 10-20 μm and 1-20 fiber layers.

5. The biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue according to claim 1, characterized in that, The geometry of the tissue-engineered fiber scaffold includes a sinusoidal network structure with different waveforms.

6. The biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue according to claim 5, characterized in that, In the sine wave or sine network structure, the amplitude of the sine wave is 100-200μm, the period is 200-600μm, and the fiber spacing is 200-800μm.

7. The method for preparing a biomimetic myocardial electronic patch with personalized adaptability to the mechanical properties of myocardial soft tissue as described in claim 1, characterized in that, Includes the following steps: TPU is MEW printed to obtain stretchable flexible fibers; The surface of the stretchable flexible fiber is coated with a gold nanolayer and a PDMS passivation layer using a spray coating technique to obtain a stretchable flexible fiber electrode. The PCL was MEW printed on the surface of the stretchable flexible fiber electrode to obtain the biomimetic myocardial electronic patch that is personalized to adapt the mechanical properties of myocardial soft tissue.

8. The preparation method according to claim 7, characterized in that, The MEW printing conditions for the stretchable flexible fiber electrode include: heating TPU to form a TPU melt, the pumping pressure of the TPU melt being 20-40 kPa, the distance from the printhead to the receiving plate being 3-5 mm, the applied voltage being 2-4 kV, and the printing speed being 800-1400 mm / min.

9. The preparation method according to claim 7, characterized in that, The MEW printing conditions for the tissue-engineered fiber scaffold include: heating PCL to form a PCL melt, the pumping pressure of the melt being 7.5-8.5 kPa, placing a stretchable flexible fiber electrode between the print head and the receiving plate, the distance between the print head and the receiving plate being 3-4 mm, applying a voltage of 4-5 kV, and printing at a speed of 200-400 mm / min.

10. The biomimetic myocardial electronic patch with personalized adaptation to the mechanical properties of myocardial soft tissue as described in claim 1, characterized in that, The mechanical properties of the tissue-engineered scaffold are individually adapted to the mechanical properties of myocardial soft tissue. The mechanical parameters of the fiber scaffold include Young's modulus of 0.05 to 0.5 MPa, elastic strain of 10-22%, and anisotropic modulus ratio of 1.9 to 3.9.

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