CN113559320B - A three-dimensional conductive melt-blown nonwoven fabric myocardial patch with multi-scale fibers and negative Poisson's ratio - Google Patents

Abstract

The invention discloses a multi-scale fiber negative Poisson ratio three-dimensional conductive melt-blown non-woven fabric myocardial patch, which is prepared by taking a shape memory polymer with a conductive function as a raw material and adopting a melt-blown non-woven fabric processing method to obtain a non-woven fabric with mixed fiber distribution of nano-micron mixed scale, and can better simulate a nano-micron fiber network structure of myocardial tissue extracellular matrix (ECM). The non-woven fabric is formed by overlapping a plurality of layers of fiber webs, wherein the nano-micron fibers have certain directionality and are matched with the laminated structures of the myocardial tissues in the long axis direction and the short axis direction and the ordered arrangement structure of the ECM, and the structure and the performance of the non-woven fabric are changed in a negative Poisson ratio. The melt-blown non-woven fabric also has good electrical conductivity, a stable signal conduction function, an elastic deformation function and good mechanical properties, and the negative Poisson ratio under different strains can be matched with the negative Poisson ratio deformation of contraction and relaxation of myocardial tissues, so that the myocardial tissues can be well simulated.

Description

A three-dimensional conductive melt-blown nonwoven fabric myocardial patch with multi-scale fibers and negative Poisson's ratio

technical field

The invention relates to a multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown nonwoven fabric myocardial patch.

Background technique

Myocardial infarction seriously threatens human health and life, and brings a heavy burden to society and families. However, the current treatment methods for myocardial infarction are not ideal. After myocardial infarction, the damaged cardiomyocytes die irreversibly and are replaced by dense collagen scar tissue, while the surviving cardiomyocytes cannot replenish the lost cells through their own proliferation and differentiation, and can only undergo compensatory hypertrophy. , eventually triggering the remodeling and enlargement of the left ventricle, leading to the occurrence of heart failure. The structure and properties of myocardial tissue are different in the long axis and short axis direction, with an anisotropic structure, and both long axis and short axis directions show negative Poisson's ratio effect. Therefore, reconstruction of functional myocardium to replace scar tissue by means of regenerative medicine will be an ideal way to effectively restore cardiac function.

It is a promising way to treat myocardial infarction by engineering myocardial patch. The patch needs to be able to mimic the structure of native myocardium and have some functions, such as inducing cardiomyocyte attachment and growth, promoting myocardial functionalization in vitro, and repairing the infarct site in vivo. An ideal myocardial patch should have the following characteristics: 1. The scaffold material has good elasticity, extensibility, stability, plasticity and certain mechanical strength, and will not damage the scaffold due to the beating of muscle cells. 2. It has good biocompatibility and does not cause inflammation, toxicity and immune rejection in the body. 3. The myocardial patch has the ability of synchronous contraction and good electrical conductivity to conduct bioelectricity and avoid serious arrhythmia after transplantation in the body.

The melt-blown method was developed in the 1950s. Its production process is to use high-melt index polymer slices. The process in which the thin stream of melt ejected from the spinneret is blown into very fine fibers, gathered into a fiber web on the receiving device, and bonded and entangled with each other to form a cloth by using its own waste heat.

Under the action of this high-temperature, high-speed airflow, the melt will be drawn into filaments with a fineness of only 1-5μm, and at the same time, these fine filaments will be broken into short fibers of 40-70mm by the drafting airflow. Then, under the guidance of the drafting airflow, these short fibers fall on the web forming machine and are bonded to each other on the web forming machine by their own waste heat to form a continuous fiber web. After the continuous fiber web is formed on the web forming machine, it is wound into a roll by the winding machine and cut by the slitting machine, and finally forms a melt-blown non-woven fabric product.

Melt-blown nonwoven technology is an important means of manufacturing nanofiber materials at present. It has the remarkable characteristics of short process flow, simple equipment, and fine fibers (fiber diameters reach micron or even sub-nanometer levels). Melt-blown nonwovens are mainly used as composite materials, filter materials, thermal insulation materials, sanitary products, oil-absorbing materials, cleaning cloths (wiping cloths), battery separators, etc., and are widely used in medical and health care, automobile industry, filter materials, and environmental protection and other fields. In foreign countries, meltblown nonwovens are mainly used as two-step SMS materials, medical and sanitary materials and covering materials. In addition, wiping and absorbing materials, filtering and barrier materials are also important uses of meltblown fabrics.

Melt-blown nano/micron nonwoven fabrics for air filtration can be prepared by using a high-speed hot air blowing method, and the fiber diameter is 200nm-10μm. The fiber diameter can be rapidly reduced by high-speed hot air stretching, and multi-scale fibers can be prepared. During the air-stretching process, the fibers are preferentially aligned in the MD direction, forming an ordered structure. By adjusting the fiber arrangement, pores and layered structure, anisotropic changes can be realized, and the negative Poisson's ratio effect of nonwovens can be realized. Under the condition of 5% unidirectional strain, γ is -0.80±0.3, which is consistent with the negative Poisson of myocardial patch. Loose ratio deformation requirements have a significant role in reducing wall stress and reducing hypertrophy.

Scaffolds for constructing tissue-engineered myocardial patches should have high porosity, good mechanical properties, biodegradability, biocompatibility, and provide a microenvironment similar to extracellular matrix. Materials for constructing tissue-engineered myocardial patches include natural materials (collagen, fibrin, chitosan, natural ECM, peptides, etc.) and synthetic materials (such as PCL). Nano-micron fiber nonwovens can be prepared by melt blown processing, but its application fields are mainly filtration and separation, protective clothing, masks, etc., and there are no technical reports on melt blown nonwoven patches in the field of myocardial tissue repair.

Contents of the invention

The invention provides a multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown nonwoven fabric myocardial patch.

The scheme that the present invention adopts is as follows:

A multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown nonwoven myocardial patch, the polymer obtained by in-situ polymerization of thermoplastic bio-polyurethane TPU and aniline monomer ANI is used as the raw material to prepare nano-scale fibers and micro-scale fibers Myocardial patch of non-woven fabric distributed in a specific way, the electrical conductivity of the non-woven fabric is 5×10 ^-5 -1.6×10 ^-3 S/cm, the modulus is 200-500kPa, and the hardness is 0.02-0.50MPa. The negative Poisson's ratio under different strains of 10-20% is -1.1-0.5, which can simulate myocardial tissue. The nanofiber arrangement has a certain directionality, and the fibers are arranged along the longitudinal orientation, showing anisotropy, which is consistent with the layered structure in the long axis and short axis direction of myocardial tissue, the ordered arrangement and anisotropic structure of ECM.

The preparation method of the multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown nonwoven myocardial patch comprises the following steps:

1) In situ polymerization of thermoplastic bio-polyurethane TPU and aniline monomer ANI to prepare shape memory polymer PANI/TPU with conductive function; the doping acid used is H ₂ SO ₄ at a concentration of 0.5mol/L, and the oxidant ammonium sulfate The concentration is 0.2mol/L, the ratio of ANI and TPU is 1:2, and the reaction time is 60min to obtain elastic conductive polymer.

2) Regulate the melt-blowing process parameters, use the high-speed airflow melt-blowing method, the air gap width is 0.1mm, the temperature of the three areas of the screw is 170°C, 230°C, 260°C, and the die head temperature is 240°C. Micro-melt-blown testing machine with hole diameter, screw length-to-diameter ratio L/D=28:1, screw speed 60r/min, hot air temperature 320°C, hot air pressure 0.6MPa and receiving distance 20cm to prepare melt blown Spray nonwoven fabric;

3) The non-woven fabric myocardial patch is laminated by multiple layers of fiber webs, each layer of fiber webs is composed of fibers with mixed scales of nano and micrometers, and the fiber diameter is controlled to be 200nm-4μm, and the thickness of the laminated multi-layer fiber webs is 200 -400 μm, in which all the fibers constituting the nonwoven are arranged in the same direction, and the deviation does not exceed 10°.

The invention utilizes high-speed airflow stretching to realize precise control of the fiber diameter; adjusts the orientation distribution of the fiber by increasing the distance and rotational speed parameters of the receiving roller, and increases the air pressure process to prepare nano-micron multi-scale mixed distribution melt-blown fibers. The nano-micron fiber melt-blown nonwoven fabric is prepared by adjusting the distance, rotational speed and air pressure parameters of the receiving roller, so that the fibers are oriented and arranged in the longitudinal direction (MD) of the melt-blown nonwoven fabric, showing anisotropic structural characteristics.

In the present invention, by designing the material system, polyurethane and aniline monomer (ANI) are used for in-situ polymerization to prepare a shape-memory polymer with conductive function, which can form an electromechanical signal pathway in the myocardial infarction area, and through structural design, utilize the conductive function The shape-memory polymer fiber can match the ordered structure of the extracellular matrix of myocardial tissue, and match the layered thickness of myocardial tissue; it can simulate the nanometer fiber network structure of the extracellular matrix of myocardial tissue. By designing the degree of oriented fiber arrangement in the longitudinal direction of the melt-blown nonwoven fabric, the arrangement of the fibers in the longitudinal and transverse directions is different, showing anisotropic structural characteristics. When stretching, under different strain conditions, the properties of the melt-blown nonwovens in the longitudinal and transverse directions are different, showing anisotropic performance changes, and the melt-blown nonwovens have a negative Poisson's ratio under 10-20% strain It is -1.1～-0.5. The mechanical properties and electrical conductivity of meltblown nonwovens are anisotropic.

The properties of the nonwoven fabric prepared by the present invention can reach the theoretical range of myocardial tissue, its elastic deformation can better simulate the deformation requirements of myocardial contraction and relaxation, and the modulus and hardness of the nonwoven fabric can provide good mechanical strength , to play a supporting effect, in addition, through the regulation of negative Poisson's ratio of different strains, it can match the negative Poisson's ratio deformation of myocardial tissue contraction and relaxation.

The invention utilizes shape memory polymers with conductive functions to promote electrical signal conduction in the myocardial infarction area and improve electrical conductivity. By regulating the high-speed airflow drafting process of the melt-blown nonwoven fabric preparation process, high-speed hot air is used to stretch the as-spun filaments, so that The fiber diameter reaches the mixed range of nanometer scale and micrometer scale, and the nanometer fiber melt-blown nonwoven fabric is prepared to simulate the fiber network structure of the ECM in the myocardial infarction area and reconstruct the bionic microenvironment. The nano-micron fibers and directional arrangement in the melt-blown nonwoven fabric prepared by the present invention, the superimposed structure of multi-layer webs, the anisotropy ratio between the longitudinal direction and the transverse direction, good electrical conductivity and stable signal transmission, elastic deformation, and mechanical properties And the negative Poisson's ratio effect can be consistent with the layered structure of myocardial tissue while simulating the ECM structure, simulating the anisotropic structural characteristics of myocardial tissue, maintaining the deformation requirements of normal myocardial contraction and relaxation, and providing the mechanical strength of myocardial tissue. Under different strains, it can match the negative Poisson's ratio deformation of myocardial tissue contraction and relaxation, promote electrical signal conduction in the infarct area, and rebuild myocardial function.

Description of drawings

Fig. 1 is the schematic diagram of the three-dimensional negative Poisson's ratio deformation structure myocardial patch of the nano-micron melt-blown nonwoven fabric of embodiment 1;

Fig. 2 is a schematic diagram of a myocardial patch with a two-dimensional negative Poisson's ratio deformed structure of the nano-micron melt-blown nonwoven fabric of Example 1.

Detailed ways

The present invention will be further described below in conjunction with the accompanying drawings and specific examples.

Example 1

The thermoplastic bio-polyurethane TPU and aniline monomer ANI were polymerized in situ to prepare the conductive shape memory polymer PANI/TPU; the doping acid used was H ₂ SO ₄ at a concentration of 0.5mol/L, and the concentration of the oxidant ammonium sulfate was 0.2mol/L, the ratio of ANI to TPU is 1:2, and the reaction time is 60min to obtain elastic conductive polymer.

Control the melt-blown process parameters, use the high-speed airflow melt-blown method, the air gap width is 0.1mm, the temperature of the three areas of the screw is 170°C, 230°C, 260°C, the die temperature is 240°C, and the spinneret hole is 0.02mm The diameter of the micro-melt-blown testing machine, the screw length-to-diameter ratio L/D=28:1, the screw speed is 60r/min, the hot air temperature is 320°C, the hot air pressure is 0.6MPa and the receiving distance is 20cm. cloth.

The fiber diameter of the melt-blown nonwoven fabric is 200nm-4μm, and the thickness of the laminated multi-layer fiber web is 200-400μm, wherein all the fibers constituting the nonwoven fabric are arranged along the longitudinal orientation. The electrical conductivity is 5×10 ^-5 -1.6×10 ^-3 S/cm, the modulus is 200-500kPa, the hardness is 0.02-0.50MPa, and the negative Poisson's ratio is -1.1～- at different strains of 10-20%. 0.5, it can simulate myocardial tissue and anisotropic deformation.

Example 2

The thermoplastic bio-polyurethane TPU and aniline monomer ANI were polymerized in situ to prepare the conductive shape memory polymer PANI/TPU; the doping acid used was H ₂ SO ₄ at a concentration of 0.5mol/L, and the concentration of the oxidant ammonium sulfate was 0.2mol/L, the ratio of ANI to TPU is 1:2, and the reaction time is 60min to obtain elastic conductive polymer.

Adjusting the parameters of the melt-blown process, when high-speed airflow is not used for stretching, the fiber diameter of the obtained melt-blown cloth is much larger than 4 μm, which cannot simulate the ultrafine fiber network structure characteristics of the extracellular matrix of myocardial tissue, and cannot effectively prevent myocardial infarction. Functional reconstruction effect of treatment.

Example 3

The thermoplastic bio-polyurethane TPU and aniline monomer ANI were polymerized in situ to prepare the conductive shape memory polymer PANI/TPU; the doping acid used was H ₂ SO ₄ at a concentration of 0.5mol/L, and the concentration of the oxidant ammonium sulfate was 0.2mol/L, the ratio of ANI to TPU is 1:2, and the reaction time is 60min to obtain elastic conductive polymer.

Adjust the melt-blown process parameters. When the speed of the receiving roller is less than 60rpm, the longitudinal arrangement of the fibers is random, and the orientation arrangement cannot be well achieved. At this time, the melt-blown cloth is close to isotropic performance changes and does not have anisotropy requirements. , does not meet the deformation requirements of the myocardial patch.

Example 4

Thermoplastic bio-polyurethane TPU is used to control the parameters of the melt-blowing process. The high-speed airflow melt-blowing method is used. The width of the air gap is 0.1mm. A micro-melt blown testing machine with a diameter of 0.02mm spinneret hole is used, the length-to-diameter ratio of the screw is L/D=28:1, the screw speed is 60r/min, the hot air temperature is 320°C, the hot air pressure is 0.6MPa and the receiving distance is 20cm of meltblown nonwoven fabric. The melt-blown nonwoven fabric prepared in this embodiment has good elastic deformation, but does not have electrical conductivity, cannot achieve the effect of signal transmission, and cannot achieve the purpose of myocardial function reconstruction.

Example 5

When using aniline monomer for melt-blown processing experiments, due to the infusibility of the conductive polymer, it is impossible to perform a single-component melt-blown process, so it cannot form a melt-blown nonwoven fabric, let alone simulate myocardial tissue.

Claims (3)

1. A multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown nonwoven myocardial patch, characterized in that the polymer obtained by in-situ polymerization of thermoplastic bio-polyurethane TPU and aniline monomer ANI is used as a raw material to prepare nano A non-woven myocardial patch in which fiber and micron-scale fibers are distributed in a longitudinal orientation; the non-woven fabric is obtained by laminating multiple layers of fiber webs, and each layer of fiber web is composed of fibers with nano-micron mixed scales, and the fiber diameter distribution is 200nm-4μm, the preparation method of the myocardial patch comprises the following steps: 1) Conduct in _- situ polymerization of thermoplastic bio-polyurethane TPU and aniline monomer ANI to prepare shape memory polymer PANI/TPU with conductive _function ; The concentration of ammonium sulfate is 0.2-0.5mol/L, the ratio of ANI to TPU is 1:2-1:4, and the reaction time is 10-60min to obtain an elastic conductive polymer; 2) The elastic conductive polymer prepared in step 1) is processed by melt-blown equipment to prepare a non-woven myocardial patch with nano-micron multi-scale mixed distribution. The parameters of the melt-blown equipment are: the width of the air gap is 0.1 -0.4mm, the temperature of the three zones of the screw is 160-170°C, 230-240°C, 260-270°C respectively, the temperature of the die head is 240-270°C, the distance of the receiving roller is 20-60cm, and the speed of the receiving roller is 60-100rpm , the high-speed air pressure is 0.4-0.6MPa. 2. The multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown nonwoven myocardial patch according to claim 1, characterized in that, in the nonwoven fabric, the fiber diameter distribution is 200nm-4μm, and the multilayer fiber net The laminated thickness is 200-400 μm, and all the fibers constituting the nonwoven fabric are arranged in the same direction, and the arrangement angle is 80-90°. 3. The multi-scale fiber negative Poisson's ratio three-dimensional conductive melt-blown non-woven myocardial patch according to claim 1, characterized in that the electrical conductivity of the non-woven fabric is 5×10 ^-5 -1.6×10 ^{- 3} S/cm, the modulus is 200-500kPa, the hardness is 0.02-0.50MPa, and the negative Poisson's ratio is -1.1～-0.5 under different strains of 10-20%.

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