CN112089893A

CN112089893A - Preparation method of high-breathability elastic nanofiber heart patch with controllable conductivity and viscosity

Info

Publication number: CN112089893A
Application number: CN202010789724.4A
Authority: CN
Inventors: 冯建永; 肖霜
Original assignee: Zhejiang University of Technology ZJUT
Current assignee: Zhejiang University of Technology ZJUT
Priority date: 2020-08-07
Filing date: 2020-08-07
Publication date: 2020-12-18
Anticipated expiration: 2040-08-07
Also published as: CN112089893B

Abstract

The invention discloses a preparation method of a high-breathability elastic nanofiber heart patch with controllable conductivity and viscosity, which comprises the following steps: mixing Polyurethane (PU), Polyaniline (PANI), and silicon dioxide (SiO)₂) Mixing, preparing spinning solution, and regulating PU, PANI and SiO respectively₂The concentration of the nano-fiber membrane is controlled, the conductivity and the viscosity of the spinning solution are accurately regulated, the electrostatic spinning equipment is used for spinning, the spinning temperature, the spinning humidity, the sliding table speed, the spinning voltage, the liquid supply speed, the distance and the rotating speed are accurately set, the nano-fiber membrane is prepared, and then the high-breathability elastic membrane is prepared through the drying processA nanofiber heart patch. The prepared high-permeability elastic nanofiber heart patch has controllable thickness, good air permeability, nano-scale fiber diameter and small pores, and excellent mechanical strength and elastic elongation. Meets the structure and performance requirements of the myocardial patch, and can be applied to the field of cardiac tissue engineering.

Description

Preparation method of high-breathability elastic nanofiber heart patch with controllable conductivity and viscosity

Technical Field

The invention relates to a preparation method of a high-breathability elastic nanofiber heart patch with controllable conductivity and viscosity.

Background

There are approximately 3800 ten thousand Heart Failure (HF) cases worldwide, and the case numbers show an annual explosive trend. Clinical results indicate that more than half of the patients with heart failure die within five years of diagnosis. Currently, the treatment for heart failure is mainly divided into two areas: one is drug therapy and the other is heart transplantation. The drug therapy only can improve the cardiac function and relieve the heart failure, and the heart failure cannot be cured fundamentally; heart transplantation, while effective in treating heart failure, does not completely eradicate recurrence at the high cost of treatment.

Aiming at the functional repair of myocardial infarction, the adopted treatment methods comprise medicines, thrombolytic treatment, coronary artery bypass operation and the like. The drug therapy is one or more drug therapies, which can reduce the workload of heart function, increase the heart contractility, improve the heart function and heart rate, however, the method can only relieve the heart failure and can not effectively reverse the symptoms of the heart failure, and thrombolytic therapy and coronary artery bypass surgery can not fundamentally repair damaged cardiac muscle, block the progress of disease course, and finally still can cause heart failure and malignant arrhythmia.

The ECM of native myocardial tissue is composed of nano and micro mixed-scale fibers (fibers are in the size range of about 75nm to 2.2 μm), and as the ECM is gradually stacked and the thickness of the fiber layer is increased, the fibers form a highly ordered, interconnected and intertwined anisotropic layered network structure, which provides structural support, elasticity and rigidity for the heart, and cells are embedded in the ECM fiber network structure to construct a cell reaction environment, regulate biochemical, biophysical and bioelectrical signal clues, and mediate cell-cell and cell-ECM interactions.

The heart patch is a new treatment mode aiming at the functional repair of myocardial infarction. A good cardiac patch should have the following characteristics: the patch has good biocompatibility, a structure with a fiber form capable of simulating extracellular matrix (ECM), certain electric conductivity and mechanical properties, and a certain thickness and pore structure. The dominant role in cell survival, vascularization and microvascular architecture can be regulated through the nano/micron structure and topology, and the fiber characteristics of the ECM are accurately simulated. The mutually communicated porous structure patch is beneficial to migration, vascularization, diffusion of nutrients, metabolites and oxygen of cells, high cell density is realized, obvious regional function difference is avoided, and long-term ideal diastolic function is realized. The porous fiber arrangement can construct the micro-environment structure of the natural cardiac muscle, provide biophysical characteristics, accurately guide the growth of cells in a three-dimensional space and promote tissue regeneration.

The heart patch reported in the prior literature mainly comprises a gel patch, an animal tissue acellular matrix heart patch, a concave-convex plane patch and the like. These patches have some disadvantages during clinical application, such as not ideal stretching and resilience to mimic systolic relaxation, not being able to mimic the nanofibrous morphology of cardiac tissue ECM, and not ideal penetration properties, not being able to match cardiac tissue well (q. -z.chen, s.e.harding, n.n.ali, a.r.lyon, a.r.boccaccini, mater.sci.eng, R2008, 59, 1; k.l.christman, r.j.lee, j.am.col.cardiol.2006, 48,907; m.a.laflamme, c.e.murry, nat.biotechnol.2005,23,845; se.s.race, n.d.evans, m.m.stevens, nat.mater.2009,8,457; a.a.ran, k.l.chord, sai.l.pacific.2011.2011.flati.r.t.r.t.r.t. r.t.r.t.r.t.r.t.t.t.r.t.t.t.t.t.r.t.t.r.t.t.r.t.t.t.t. k.r.t. k.t. k.

Due to the superior performance of the nano-fiber and the defects of the heart patch in the prior literature, the high-air-permeability elastic nano-fiber heart patch with controllable conductivity and viscosity is prepared by the accurate design of a material system and an electrostatic spinning method.

Disclosure of Invention

The invention aims to provide a preparation method of a high-breathability elastic nanofiber heart patch aiming at the defects in the prior art.

The invention is realized by adopting the following technical scheme:

a preparation method of a high-breathability elastic nanofiber heart patch comprises the following steps:

1) mixing Polyurethane (PU), Polyaniline (PANI), and silicon dioxide (SiO)₂) Are completely dissolved in N, N-Dimethylformamide (DMF) to obtain spinning solution; wherein the mass concentration of PU is 5-7%, the mass concentration of PANI is 1-9%, and SiO is₂The mass concentration of the active carbon is 0 to 0.5 percent;

2) taking the spinning solution obtained in the step 1), and spinning by using electrostatic spinning equipment to prepare a nanofiber membrane;

3) drying the nanofiber membrane obtained in the step 2) for 10-30min at the temperature of 50-60 ℃. The high-permeability elastic nanofiber heart patch can be obtained by regulating and controlling the drying temperature and time to completely volatilize the residual solvent N, N-dimethylformamide.

In the above technical solution, further, in the step 1), the polyurethane is prepared by PU, PANI and SiO₂The concentration of (2) is changed, the conductivity of the spinning solution is 45.8-179.9 mu S/cm, and the viscosity is 835.8-4729 mPas.

Further, the parameters during electrostatic spinning are as follows: the temperature is 35-37.9 ℃, the humidity is 30-34.8%, the sliding table speed is 12-15mm/s, the spinning voltage is 12-15kv, the liquid supply speed is 0.8-1mL/h, the distance is 8-10cm, and the rotating speed is 200-300 rad/min.

The invention has the beneficial effects that:

the method has simple process, and the PU, the PANI and the SiO are mixed₂And completely dissolving the mixture in DMF to obtain a spinning solution, and regulating and controlling the conductivity and viscosity of the spinning solution through the concentration change of the additive. And (3) precisely controlling the spinning temperature, the spinning humidity, the sliding table speed, the spinning voltage, the liquid supply speed, the distance and the rotating speed by using an electrostatic spinning method to prepare the nanofiber membrane. And (3) completely volatilizing the residual solvent DMF by regulating and controlling the drying temperature and time to obtain the high-breathability elastic nanofiber heart patch.

The prepared high-permeability elastic nanofiber heart patch has the thickness of 0.03-0.15mm, the air permeability of 8.8-125.31mm/s, the contact angle of water of 129.2-130.1 degrees, the fiber diameter of 217-542nm, the pore diameter of 574-890nm, the tensile stress of 7.71×10⁴-1.64×10⁶N, tensile strain 106.5-115.75%. By adding PU, PANI and SiO₂The thickness, air permeability, contact angle, fiber diameter, pore diameter, tensile stress and tensile strain of the patch can be regulated and controlled by the change of concentration, the change of spinning temperature, humidity, sliding table speed, spinning voltage, liquid supply speed, distance and rotating speed, and the change of drying temperature and time.

The prepared high-air-permeability elastic nanofiber heart patch has the advantages of nanoscale fiber diameter, pore size and micrometer-scale thickness, and can accurately simulate a multilayer ordered, nano/micrometer multi-scale fiber network structure of myocardial tissue extracellular matrix (ECM). Certain porous structure and air permeability can be used for conveying nutrient substances for cell growth and facilitating excretion of metabolites. The tensile stress and strain may provide the deformation requirements for contraction and relaxation of the host myocardium, providing mechanical support.

Compared with hydrogel and composite microspheres of the traditional heart patch, the high-breathability elastic nanofiber heart patch prepared by the invention has controllable thickness, good breathability, nano-scale fiber diameter and small pores, and excellent mechanical strength and elastic elongation. Meets the structure and performance requirements of the myocardial patch, and can be applied to the field of cardiac tissue engineering.

Drawings

FIG. 1 is a scanning electron micrograph of a sample prepared in example 1.

FIG. 2 is a scanning electron micrograph of the sample prepared in example 2.

FIG. 3 is a scanning electron micrograph of the sample prepared in example 3.

FIG. 4 is a scanning electron micrograph of the sample prepared in example 4.

Detailed Description

The present invention is further illustrated by the following examples.

Example 1:

mixing Polyurethane (PU), Polyaniline (PANI), and silicon dioxide (SiO)₂) Putting into a stirring bottle, taking N, N-Dimethylformamide (DMF) as a solvent, stirring until the N, N-dimethylformamide is completely dissolved, wherein the total mass of a spinning solution is 10g, PU,PANI and SiO₂The concentrations of (A) were 7%, 1% and 0.5%, respectively. The spinning dope had an electric conductivity of 45.8. mu.S/cm and a viscosity of 4729 mPas. The electrostatic spinning parameters are as follows: the spinning temperature is 37.9 ℃, the humidity is 34.8%, the sliding table speed is 15mm/s, the spinning voltage is 15kv, the liquid supply speed is 1mL/h, the distance is 10cm, and the rotating speed is 300 rad/min. And drying the prepared nanofiber membrane in an oven at 60 ℃ for 10 min. Obtaining the high-permeability elastic nanofiber heart patch. The prepared nanofiber membrane heart patch has the following properties: thickness of 0.04mm, air permeability of 33.61mm/s, water contact angle of 130.1 °, fiber diameter of 542nm, pore diameter of 890nm, and tensile stress of 1.12 × 10⁶N, tensile strain 111.25%.

By adding PU, PANI and SiO₂The thickness, air permeability, contact angle, fiber diameter, pore diameter, tensile stress and tensile strain of the patch can be regulated and controlled by the change of concentration, the change of spinning temperature, humidity, sliding table speed, spinning voltage, liquid supply speed, distance and rotating speed, and the change of drying temperature and time. In this example, the PU concentration was increased and PANI and SiO were decreased₂Can significantly affect fiber diameter, tensile stress and strain, and provides good elasticity while having a contact angle on the surface of the film>90 degrees, has the characteristics of porosity and hydrophobicity.

Example 2:

polyurethane (PU) and Polyaniline (PANI) are put into a stirring bottle, N-Dimethylformamide (DMF) is taken as a solvent, stirring is carried out until the polyurethane and the polyaniline are completely dissolved, the total mass of a spinning solution is 10g, and the concentrations of the PU and the PANI are respectively 5 percent and 3 percent. The spinning solution had an electric conductivity of 97.8. mu.S/cm and a viscosity of 945.7 mPas. The electrostatic spinning parameters are as follows: the spinning temperature is 35 ℃, the humidity is 30%, the sliding table speed is 12mm/s, the spinning voltage is 12kv, the liquid supply speed is 0.8mL/h, the distance is 8cm, and the rotating speed is 200 rad/min. And drying the prepared nanofiber membrane for 10min in an oven at the temperature of 50 ℃. Obtaining the high-permeability elastic nanofiber heart patch. The prepared nanofiber membrane heart patch has the following properties: thickness of 0.04mm, air permeability of 19.95mm/s, contact angle of water of 129.2 °, fiber diameter of 264nm, pore diameter of 833nm, and tensile stress of 1.64 × 10⁶N, tensile strain 115.75%.

By adding PU, PANI and SiO₂The thickness, air permeability, contact angle, fiber diameter, pore diameter, tensile stress and tensile strain of the patch can be regulated and controlled by the change of concentration, the change of spinning temperature, humidity, sliding table speed, spinning voltage, liquid supply speed, distance and rotating speed, and the change of drying temperature and time. In this example, SiO was not added₂The conductivity of the spinning solution is increased, the viscosity is reduced, the tensile stress and strain of the prepared nano film are increased, the air permeability is reduced, and the contact angle of the surface of the film is reduced>90 degrees, has the characteristics of porosity and hydrophobicity.

Example 3:

mixing Polyurethane (PU), Polyaniline (PANI), and silicon dioxide (SiO)₂) Placing into a stirring bottle, stirring with N, N-Dimethylformamide (DMF) as solvent until completely dissolving, the total mass of spinning solution is 10g, PU, PANI and SiO₂The concentrations of (A) were 5%, 9%, and 0.5%, respectively. The spinning solution had an electric conductivity of 179.9. mu.S/cm and a viscosity of 835.8 mPas. The electrostatic spinning parameters are as follows: the spinning temperature is 37.9 ℃, the humidity is 34.8%, the sliding table speed is 15mm/s, the spinning voltage is 15kv, the liquid supply speed is 1mL/h, the distance is 10cm, and the rotating speed is 300 rad/min. And drying the prepared nanofiber membrane in an oven at 60 ℃ for 10 min. Obtaining the high-permeability elastic nanofiber heart patch. The prepared nanofiber membrane heart patch has the following properties: thickness of 0.15mm, air permeability of 8.8mm/s, water contact angle of 129.2 °, fiber diameter of 217nm, pore diameter of 574nm, tensile stress of 7.71 × 10⁴N, tensile strain 106.5%.

By adding PU, PANI and SiO₂The thickness, air permeability, contact angle, fiber diameter, pore diameter, tensile stress and tensile strain of the patch can be regulated and controlled by the change of concentration, the change of spinning temperature, humidity, sliding table speed, spinning voltage, liquid supply speed, distance and rotating speed, and the change of drying temperature and time. In this example, the PANI content was increased, the conductivity of the spinning solution was increased, the viscosity was decreased, the tensile stress and strain of the prepared nano-film were decreased, the air permeability was decreased,contact angle of film surface>90 degrees, has the characteristics of porosity and hydrophobicity.

Example 4:

mixing Polyurethane (PU), Polyaniline (PANI), and silicon dioxide (SiO)₂) Placing into a stirring bottle, stirring with N, N-Dimethylformamide (DMF) as solvent until completely dissolving, the total mass of spinning solution is 10g, PU, PANI and SiO₂The concentrations of (A) were 6%, 2%, and 0.5%, respectively. The spinning solution had an electric conductivity of 73.7. mu.S/cm and a viscosity of 2947 mPas. The electrostatic spinning parameters are as follows: the spinning temperature is 37.9 ℃, the humidity is 34.8%, the sliding table speed is 15mm/s, the spinning voltage is 12kv, the liquid supply speed is 1mL/h, the distance is 8cm, and the rotating speed is 200 rad/min. And (3) drying the prepared nanofiber membrane for 20min in an oven at the temperature of 50 ℃. Obtaining the high-permeability elastic nanofiber heart patch. The prepared nanofiber membrane heart patch has the following properties: thickness of 0.03mm, air permeability of 125.31mm/s, water contact angle of 129.6 °, fiber diameter of 460nm, pore diameter of 704nm, and tensile stress of 1.07 × 10⁶N, tensile strain 109.0%.

By adding PU, PANI and SiO₂The thickness, air permeability, contact angle, fiber diameter, pore diameter, tensile stress and tensile strain of the patch can be regulated and controlled by the change of concentration, the change of spinning temperature, humidity, sliding table speed, spinning voltage, liquid supply speed, distance and rotating speed, and the change of drying temperature and time. In this embodiment, PU, PANI, SiO were changed₂The concentration and the drying condition of the nano film are changed, so that the tensile stress of the prepared nano film is increased, the strain is reduced, the air permeability is increased, and the contact angle of the surface of the film is increased>90 degrees, has the characteristics of porosity and hydrophobicity.

Claims

1. A preparation method of a high-breathability elastic nanofiber heart patch with controllable conductivity and viscosity is characterized by comprising the following steps:

1) completely dissolving polyurethane, polyaniline and silicon dioxide in N, N-dimethylformamide to obtain spinning solution; wherein, the mass concentration of polyurethane is 5-7%, the mass concentration of polyaniline is 1-9%, and the mass concentration of silicon dioxide is 0-0.5%;

3) drying the nanofiber membrane obtained in the step 2) for 10-30min at the temperature of 50-60 ℃ to obtain the high-breathability elastic nanofiber heart patch.

2. The method for preparing the highly breathable elastic nanofiber heart patch with controllable conductivity and viscosity according to claim 1, wherein in the step 1), the conductivity of the spinning solution is 45.8-179.9 μ S/cm, and the viscosity is 835.8-4729 mPa-S.

3. The method for preparing the highly breathable elastic nanofiber heart patch with controllable conductivity and viscosity according to claim 1, wherein during the electrospinning in the step 2), the temperature is 35-37.9 ℃, the humidity is 30-34.8%, the sliding table speed is 12-15mm/s, the spinning voltage is 12-15kv, the liquid supply speed is 0.8-1mL/h, the distance is 8-10cm, and the rotating speed is 200-300 rad/min.