Melt electrostatic direct writing preparation method of polymer fiber scaffold with continuous gradually-changed structure

Abstract

The invention belongs to the technical field of polymer additive manufacturing, and relates to a melt electrostatic direct writing preparation method of a polymer fiber scaffold with a continuous gradual change structure, which comprises the following steps of: designing a basic homogeneous pattern according to the transition interface characteristics of a to-be-repaired tissue, and discretizing the basic homogeneous pattern into a dense ordered point array; designing nonlinear transformation functions f and g according to structural change characteristics at a transition interface, mapping points one by one by using the nonlinear transformation functions f and g so as to obtain a point column, performing equidistant sampling on the point column to obtain an expected printing path, and finally performing melt electrostatic direct writing based on the expected printing path so as to obtain the melt electrostatic direct writing. And preparing the polymer fiber scaffold with the continuous gradually-changed structure. According to the method, a curve printing process is adopted to simulate a smooth transition interface between tissues, so that the structure and mechanical bionic degree of the polymer fiber scaffold are improved.

Description

Technical Field

[0001] The present invention belongs to the technical field of polymer additive manufacturing, and relates to a method for preparing a melt electrospinning direct writing of a polymer fiber scaffold with a continuously gradually changing structure. Background Art

[0002] Melt electrospinning direct writing (MEW) is a novel method for preparing thermoplastic polymer fiber scaffolds, which has the following advantages: no organic solvents are required during the printing process, and there is no problem of biological toxicity caused by organic solvents; the printing fiber resolution is high, and micron or sub-micron scale fibers can be printed, which is comparable to the cell diameter; the range of processable materials is wide; the microstructure can be customized. Based on the above advantages, MEW scaffolds can highly mimic the complex structure and biomechanical properties of the extracellular matrix, and regulate the behaviors of cell adhesion, proliferation, migration, and differentiation, thus promoting tissue regeneration and reconstruction. Therefore, MEW scaffolds have been widely used in tissue engineering and regenerative medicine (TERM).

[0003] The structure of MEW scaffolds aims to mimic the extracellular matrix structure of native tissues in the human body and improve the bionic degree. However, there are a large number of different transitional zone tissue structures in the human body, such as osteochondral tissue, tendon / ligament-bone interface tissue, heart valve tissue, etc. Therefore, the preparation of bionic scaffolds with heterogeneous structures has important tissue engineering significance.

[0004] At present, there are mainly two strategies for the design of heterogeneous bionic scaffolds: interlayer gradient and intralayer gradient.

[0005] For the interlayer gradient design, for example, in Reference 1 (Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration - ScienceDirect[J]. Biomaterials, 266[2025-06-17]. DOI: 10.1016 / j.biomaterials.2020.120385.), a three-layer scaffold was designed to simulate the gradual transition from cartilage to subchondral bone by increasing the fiber spacing layer by layer and changing the interlayer angle; in Reference 2 (Melt Electrowriting of Graded Porous Scaffolds to Mimic the Matrix Structure of the Human Trabecular Meshwork. ACS Biomater Sci Eng 2022, 8, 3899.), a three-layer scaffold similar to the human trabecular mesh was constructed by regulating the fiber spacing and orientation; in Reference 3 (Designing Outside the Box: Unlocking the Geometric Freedom of Melt Electrowriting using Microscale Layer Shifting[J]. Advanced Materials, 2020, 32(28). DOI: 10.1002 / adma.202001874.), an interlayer path offset strategy was further proposed to construct a new structure by increasing the displacement layer by layer, significantly improving the design freedom of the MEW scaffold.

[0006] However, although the interlayer gradient design is relatively simple, it is not suitable for the case where the structural gradient feature and the fiber direction are coplanar, such as tendon / ligament-bone interface tissue and heart valve tissue. For these application scenarios, the strategy of "zoned homogeneous structure design + splicing between regions" is mainly adopted to achieve the intra-layer gradient. For example, in Reference 4 (Fabrication of bioinspired grid-crimp micropatterns by melt electrospinning writing for bone-ligament interface study[J].Biofabrication, 2022, 14(2). DOI:10.1088 / 1758-5090 / ac4ac8.), a grid-crimp pattern was designed, with a 0 / 90° grid at the bone end and a wavy pattern at the ligament end, and the interface region between the two parts was formed by the overlap of the two patterns;

[0007] Reference 5 (Spatially Heterogeneous Tubular Scaffolds for In Situ Heart Valve Tissue Engineering Using Melt Electrowriting[J].Advanced Functional Materials, 2022, 32(21).) designed an additional enhanced suture structure in the interface region based on Reference 4 using a dedicated algorithm;

[0008] Different from the heterogeneous patterns formed by zoning, Reference 6 (Melt electrowriting of high-precision diamond-square bi-phasic scaffolds and influence on mechanical characteristics through path planning[J].Materials Letters, 2025, 385(000). DOI:10.1016 / j.matlet.2025.138175.) prepared a diamond-square biphasic scaffold, and used a clever path design to make the square grid pattern transition to the diamond in a continuous manner, forming a seamless printing path.

[0009] However, the above-mentioned in-layer gradient design strategy still has key limitations: First, the internal structure of each region is homogeneous. When joining or connecting at the interface, the continuity and smoothness of the structures of each region do not match, resulting in structural mutations and significant inter-regional interfaces, deviating from the continuous gradient characteristics of the natural tissue extracellular matrix in terms of both structure and mechanical properties. Under cyclic tensile loads, such discontinuous transition structures will cause stress concentration and premature failure at the interface due to the mismatch in the deformation behaviors of adjacent regions. Second, as the microstructural domains and their transition interfaces need to be independently parameterized, the complexity of path generation increases exponentially, restricting the large-scale preparation of bionic gradient scaffolds.

[0010] Therefore, it is of great significance to study a melt electrospinning direct writing preparation method for a structurally continuously gradient polymer fiber scaffold to solve the above problems. Summary of the Invention

[0011] The object of the present invention is to solve the problems existing in the prior art and provide a melt electrospinning direct writing preparation method for a structurally continuously gradient polymer fiber scaffold.

[0012] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0013] A melt electrospinning direct writing preparation method for a structurally continuously gradient polymer fiber scaffold includes the following steps:

[0014] Step 1: Design a basic homogeneous pattern according to the transition interface characteristics of the tissue to be repaired and discretize it into a dense and ordered point sequence: ;

[0015] Step 2: Design non-linear transformation functions f and g according to the structural change characteristics at the transition interface. Use the non-linear transformation functions f and g to map the points of R one by one to, where, i is the point serial number, thereby obtaining the point sequence; one by one into where ,, i is the point serial number, so as to obtain the point sequence ;

[0016] Step 3: The point sequence is equally sampled (the purpose is to reduce the point density) to obtain the expected printing path ;

[0017] Step 4: Based on the expected printing path, perform melt electrospinning direct writing to prepare a structurally continuously gradient polymer fiber scaffold.

[0018] As a preferred technical solution:

[0019] In the melt electrostatic direct writing preparation method of a structurally continuous gradient polymer fiber scaffold as described above, the basic homogeneous pattern in step 1 is a continuous closed line that can be completed in one stroke; and the adjacent point distance of the dense and orderly point array is less than 0.1 μm.

[0020] In the melt electrostatic direct writing preparation method of a structural continuous gradient polymer fiber scaffold as described above, in step 1, if the transition interface of the tissue to be repaired is a ligament-bone interface or a tendon-bone interface, the basic homogeneous pattern is a 0 / 90° grid, and the grid side length of the basic homogeneous pattern is 0.02~2 mm; if the transition interface of the tissue to be repaired is a heart valve, the basic homogeneous pattern is a honeycomb grid or a diamond grid, and the grid side length of the basic homogeneous pattern is 0.05~2 mm.

[0021] In the above-mentioned method for preparing a continuously gradient polymer fiber support by melt electrostatic direct writing, the nonlinear transformation functions f and g in step 2 satisfy the Jacobian formula This holds true for any point sequence in the basic homogeneous pattern R.

[0022] The choice of nonlinear transformation function is determined by the deformation effect that the user expects to produce. If a wave effect is expected, a univariate trigonometric transformation can be selected. , where and is the wave number, and is the phase shift, , Indicates the amplitude of wave deformation. The larger its value, the more obvious the wave fluctuations. If you expect to produce a periodic density effect, you can choose the two-variable trigonometric transformation or , where , Indicates the intensity of periodic oscillation deformation. The larger the value, the more severe the deformation. , To fine-tune the parameters of the deformation feature, Adjust the linear displacement in the X direction, Adjust the linear displacement in the Y direction; if you want to produce a ripple effect, you can first list the origin coordinates Convert to polar coordinates ,Right now , , and then complete the ripple transformation in polar coordinate form, that is, , where represents the reference coefficient in the radial equation, , Determines the intensity of the ripples and affects the contrast intensity of the pattern. represents the frequency, which determines how many waves appear within a given radial distance. denotes the exponential decay factor, by adjusting which the amplitude of the ripple can be made to decrease with the increase of the radial distance, and finally is converted back to the Cartesian coordinate form where the parameters can take = 1, = 0.025, = 0, = 10 or = 1, = 0.025, = 0.5, = 20, etc.; if a flower-shaped effect is expected, then with the help of the flower-shaped transformation in polar coordinate form in which the cosine term determines the angular periodicity, where n being an integer directly determines the number of petals (for example, n = 5 generates five-fold rotational symmetry), and the exponential decay factor adjusts the petal size along the radial direction, controls the size gradient from the center to the edge, is the reference coefficient, controls the intensity of the flower effect, where the parameters can take = 2, = 1, = 1, n = 8 or = 2, = 5, = 5, n = 4, etc.; if a vortex effect is expected, then with the help of the vortex transformation in polar coordinate form in which represents the reference coefficient, E represents the radial decay rate of the angular displacement, and this formula produces a spiral effect through two coupling mechanisms: radial expansion adjustment, introduces radial expansion ( > 0) or contraction ( < 0), and decays exponentially with the increase of the radius R; angular accumulation: creates a progressive distortion, where the parameter controls the maximum distortion intensity at the origin (R = 0), where the parameters can take = 1, = 2, = 0.1, = 3, etc. As a special case of the vortex transformation, if = 0, then a local circular expansion (B4 > 0) or contraction (B4 < 0) effect is produced; in the above various non-linear transformation functions, A1~A5, B1~B4, C1~C5, D1~D2, E, ~ , etc. are all user-adjustable parameters.

[0023] One or several of the non - linear transformations in Step 2 can be flexibly combined and applied sequentially to achieve a composite transformation. That is, the initial point sequence R is deformed once to obtain r1, r1 is deformed twice to obtain r2, and so on until the expected pattern point sequence r is obtained. n 。

[0024] The composite transformation can also be obtained by combining non - linear transformation and linear transformation; the types of linear transformation include translation, rotation or general regular transformation; the translation transformation function is , ,the rotation transformation function is , ,and the regular transformation function is , ,where 。

[0025] The combination method of non - linear transformation and linear transformation generally takes the following method as a unit: "the first linear transformation + non - linear transformation + the second linear transformation", where the second linear transformation is the inverse transformation of the first linear transformation; an arbitrary number of units can be included in a combination.

[0026] When it is necessary to limit the deformation area, the coefficients (such as A1, A2, C1, C1, etc.) in the single - variable or bivariate trigonometric transformation function or the exponential decay term in other non - linear transformations ( 、 、 and )can be replaced by a confinement factor , corresponding to a specific confinement area (the confinement area is customized by the user). Inside the confinement area ( ), full deformation is applied, and no deformation occurs outside ( ). In the boundary transition area, it linearly decays from 1 to 0 from the inner boundary to the outer boundary of the transition area.

[0027] For the melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold as described above, the sampling distance in Step 3 is 10 - 200 μm. The sampling distance refers to selecting a point at a certain distance (such as 10 μm), and the points with a distance less than this value are deleted.

[0028] For the melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold as described above, the specific process of Step 4 is as follows: Select an appropriate jet lag length value and jet deposition rate, generate the actual motion trajectory and motion rate of the X - Y moving platform based on the expected printing path and curve printing theory, and execute the printing process, including the following steps:

[0029] Step a: Calculate the jet deposition rate according to the expected fiber diameter and monitor the current jet lag length value l in real time, where is the melt flow rate, which can be adjusted by the feeding air pressure; use the online monitoring device for melt electro-writing jet lag in Patent CN202510392215.0 to monitor the jet lag length during the curve printing process in real time; the online monitoring device for melt electro-writing jet lag includes a servo motor, an industrial camera, an annular guide rail and a load-bearing bracket. The servo motor and the industrial camera are both fixed on the slider of the annular guide rail. The servo motor drives the industrial camera to move along the annular guide rail. The annular guide rail is fixed on the gantry of the melt electro-writing device through the load-bearing bracket, and the annular guide rail is coaxial with the center line of the melt electro-writing nozzle; the servo motor drives the industrial camera to move on the annular guide rail at a certain speed, and takes pictures in real time during the movement and obtains the jet lag length during the curve printing process from them; the speed at which the servo motor drives the industrial camera to move on the annular guide rail is ; where R is the radius of the annular guide rail, in mm; ; , and are respectively the local curvature of the deposition trajectory, the unit tangent vector and the deposition rate at the real-time deposition point of the fiber. The unit of the local curvature of the deposition trajectory is mm -1 , the unit of the unit tangent vector is 1, and the unit of the deposition rate is mm / s;

[0030] Step b: Adjust process parameters such as voltage and electrode spacing, etc., so that the electrostatic direct writing system controls the jet lag length within the range of 1 - 3 mm in the stable printing state to ensure the stability of the printing process, and continuously adjust the printing path according to the monitored jet lag length l;

[0031] Step c: Generate the actual motion trajectory and motion rate of the X-Y moving platform according to the curve printing theory under steady state and input them into the motion platform controller of the electrostatic direct writing system to perform the printing process.

[0032] For the melt electrospinning preparation method of a structurally continuously gradient polymer fiber scaffold as described above, the fiber diameter in Step a is 5 - 50 μm.

[0033] For the melt electrospinning preparation method of a structurally continuously gradient polymer fiber scaffold as described above, the actual motion trajectory and motion rate of the X-Y moving platform in Step c are calculated by Formulas (1) - (4);

[0034] (1);

[0035] (2);

[0036] (3);

[0037] (4);

[0038] wherein, represents the difference operation, and i is the point number.

[0039] A method for preparing a melt electrospinning direct writing of a structurally continuously gradient polymer fiber scaffold as described above, wherein the material of the polymer fiber scaffold is polycaprolactone (PCL), polylactic acid (PLA) or poly(lactic-co-glycolic acid) (PLGA).

[0040] Beneficial effects:

[0041] (1) The present invention improves the flexibility of the melt electrospinning direct writing path design through matrix or function transformation, while increasing the degree of freedom of personalized design and the interactivity of the design process, reducing the threshold of the print path design, and improving the customizability of the path design to a greater extent.

[0042] (2) The present invention utilizes the non-linear transformation functions f and g to prepare a structurally continuously gradient polymer fiber scaffold to mimic the smooth transition interface between tissues, ensure the smooth connection and transition at the interface of different tissues, improve the structural and mechanical bionics of the polymer fiber scaffold, make the stress distribution more uniform when the designed scaffold bears force, improve the stress concentration phenomenon, and also greatly improve the diversity and richness of the micro patterns; in addition, the present invention can meet the situation where the structural gradient feature and the fiber direction are coplanar, that is, the structure is gradually changed within the same layer, which is of great significance to the melt electrospinning direct writing technology and the tissue engineering and biomedical fields it faces. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] Figure 1 is a schematic diagram of the 0 / 90° type grid of the basic homogeneous pattern of the present invention;

[0044] Figure 2 is a schematic diagram of the basic homogeneous pattern after function heterogenization of the present invention;

[0045] Figure 3 is a schematic diagram of the interface of the tissue transition interface in the present invention;

[0046] Figure 4 is a schematic diagram of the interface of the tissue transition interface in the prior art;

[0047] Figure 5Schematic diagram of the same transition interface selected during the simulated tensile test of the continuously gradient-structured polymer fiber scaffold of the present invention and the scaffold directly stacked in the prior art; in the figure, a is the schematic diagram of the transition interface selected for the continuously gradient-structured polymer fiber scaffold of the present invention, and b is the schematic diagram of the transition interface selected for the scaffold directly stacked in the prior art;

[0048] Figure 6 For Figure 5 Graph of the results of the simulated tensile test for the same transition interface selected in; in the figure, a is the simulation result of the continuously gradient-structured polymer fiber scaffold of the present invention, b is the simulation result of the scaffold directly stacked in the prior art, S, Mises represents the Mises stress, which is an equivalent stress index widely used in the engineering field, and its unit is MPa;

[0049] Figure 7 Physical prints of the continuously gradient-structured polymer fiber scaffold of the present invention and the scaffold directly stacked in the prior art; in the figure, a is the physical print of the continuously gradient-structured polymer fiber scaffold of the present invention, and b is the physical print of the scaffold directly stacked in the prior art;

[0050] Figure 8 Stress-strain curve graph of the continuously gradient-structured polymer fiber scaffold of the present invention and the scaffold directly stacked in the prior art. Specific embodiments

[0051] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and not to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of this application.

[0052] The test methods for the relevant performance indicators in the present invention are as follows:

[0053] Elastic modulus, yield stress and tensile strength: The continuously gradient-structured polymer fiber scaffold and the directly stacked scaffold are used as specimens respectively. Then, a high-strength and high-modulus fiber tensile tester is used. Under the conditions of a temperature of 20 °C and a relative humidity of 65%, specimens with a size of 5 mm × 12 mm are fixed by pneumatic clamps to reduce slippage. Then, a tensile speed of 40 mm / min is used for tensile testing, and the force-displacement data is continuously recorded until the specimen breaks. Finally, the elastic modulus, yield strength and tensile strength are calculated based on the obtained stress-strain curve.

[0054] A method for preparing a continuously gradient-structured polymer fiber scaffold by melt electrospinning writing, the steps are as follows:

[0055] Step 1: Design a basic homogeneous pattern based on the transitional interface characteristics of the tissue to be repaired and discretize it into a dense and ordered point sequence: ; Among them, if the transitional interface of the tissue to be repaired is a ligament-bone interface or a tendon-bone interface, the basic homogeneous pattern is a 0 / 90° grid composed of continuous closed lines that can be completed in one stroke, and the grid side length of the basic homogeneous pattern is 0.02 - 2 mm; if the transitional interface of the tissue to be repaired is a heart valve, the basic homogeneous pattern is a honeycomb grid or a rhombic grid composed of continuous closed lines that can be completed in one stroke, and the grid side length of the basic homogeneous pattern is 0.05 - 2 mm; the adjacent point distance of the dense and ordered point sequence is less than 0.1 μm;

[0056] Step 2: Design non-linear transformation functions f and g according to the structural change characteristics at the transitional interface. Using the non-linear transformation functions f and g, map the points of R one by one to , where , , i is the point serial number, thus obtaining the point sequence ; The non-linear transformation functions f and g satisfy the Jacobian which holds for any point sequence in the basic homogeneous pattern R;

[0057] Step 3: The point sequence obtains the expected printing path after equidistant sampling; among them, the sampling distance is 10 - 200 μm;

[0058] Step 4: Select appropriate jet lag length values and jet deposition rates, and generate the actual motion trajectory and motion rate of the X-Y moving platform based on the expected printing path and the curve printing theory, and execute the printing process, including the following steps:

[0059] Step a: Calculate the jet deposition rate according to the expected fiber diameter , and monitor the current jet lag length value l in real time, where is the melt flow rate; among them, the material of the fiber is polycaprolactone (PCL), polylactic acid (PLA) or poly(lactic-co-glycolic acid) (PLGA), and the fiber diameter is 5 - 50 μm;

[0060] Step b: Adjust the process parameters to control the jet lag length within the range of 1 - 3 mm in the stable printing state of the electrohydrodynamic direct writing system and continuously adjust the printing path according to the monitored jet lag length l;

[0061] Step c: Generate the actual motion trajectory and motion rate And input the motion platform controller of the electrostatic direct writing system to perform the printing process; among them, the actual motion trajectory of the X-Y moving platform and the motion speed are calculated through formulas (1) to (4);

[0062] (1);

[0063] (2);

[0064] (3);

[0065] (4);

[0066] Among them, represents the difference operation, and i is the point serial number;

[0067] Based on the expected printing path, melt electrospinning direct writing is carried out to prepare a polymer fiber scaffold with a continuously gradually changing structure.

[0068] Now, taking the preparation of a bone-ligament tissue bionic scaffold as an example, the above preparation method is adopted, where:

[0069] In step 1, the transition interface of the tissue to be repaired is the ligament-bone interface, and the basic homogeneous pattern is a 0 / 90° type grid composed of continuous closed lines that can be completed in one stroke, such as Figure 1 shown. The grid side length of the basic homogeneous pattern is 500 μm, and the adjacent point distance of the dense and ordered point series is 0.09 μm;

[0070] In step 2, according to the structure of the bone-ligament tissue bionic scaffold to be prepared, a wavy effect is expected to be generated. Therefore, a single-variable trigonometric transformation is selected, and the wavy effect is restricted to the left side of the bone-ligament tissue bionic scaffold and smoothly transitions into a straight line effect (that is, in area linearly decays from 1 to 0, realizing the transition from a curve to a straight line, and the amplitude changes smoothly to prevent discontinuous jumps at the deformation boundary and prevent stress concentration phenomena from occurring when the scaffold is stressed. The pattern of its ligament-bone interface is as Figure 3 shown, to imitate the structural gradual change from ligament to bone, so as to obtain a point series (the deformed basic homogeneous pattern obtained according to the point series is as Figure 2 shown); among them, the single-variable trigonometric transformation: , in the formula, is 1, and are both 1, and are respectively and , from which a point sequence is obtained The specific operations are as follows:

[0071] Take the points included in the basic pattern (0, 0), (0.1, 0), (0.2, 0) as an example. After the point (0, 0) passes through the deformation equation , , the coordinates are (0, 0.5). Similarly, (0.1, 0.5), (0.2, 0.49) can be obtained. The remaining point sequences can be calculated by the same method to obtain the deformed coordinates;

[0072] The sampling distance in step 3 is 100 μm;

[0073] In step 4, the printing temperature is 23 °C, the printing humidity is 35%, the fiber material is polycaprolactone (manufacturer: Perstorp Company, Sweden, model: CAPA6500), and the fiber diameter is 30 μm, and the melt flow rate Q is 7.63 μL / h;

[0074] First, calculate the fiber deposition rate to be 3 mm / s, and then calculate the local curvature and the unit tangent vector of each ordered point sequence according to formulas (1) to (4). Taking (0, 0.5), (0.1, 0.5), (0.2, 0.49) as an example, calculate the local curvature at this ordered point sequence 0.996 mm -1 , and the unit tangent vector (1.1, −0.05);

[0075] Then, generate the actual motion trajectory and the motion speed of the X-Y moving platform according to the curve printing theory under steady state, and input them into the motion platform controller of the electrostatic direct writing system to perform the printing process to obtain the bone-ligament tissue bionic scaffold. Among them, the number of printing layers is 8 layers. During the printing process, the printing path is continuously adjusted according to the observed real-time jet lag length l. If the jet lag length l is 1 mm, then the real-time trajectory of the point , and the speed 4.23 mm / s.

[0076] The finally obtained continuously gradient-structured polymer fiber scaffold (such as Figure 7 a in Figure 8 ) has an elastic modulus of 134.2 MPa, a yield stress of 17.9 MPa, and a tensile strength of 22.5 MPa;

[0077] Referring to the scaffold directly stacked with 8 printing layers in Reference 4 (Fabrication of bioinspired grid-crimp micropatterns by melt electrospinning writing for bone-ligament interface study[J].Biofabrication,2022, 14(2).DOI:10.1088 / 1758-5090 / ac4ac8.) (that is, first printing the tissue pattern on one side and then printing the tissue pattern on the other side, ensuring that there is a certain overlapping area between the two parts to form a whole), where the transition interface is as Figure 4 shown; the elastic modulus of the directly stacked scaffold (such as Figure 7 b in Figure 8 ) is 66.9 MPa, the yield strength is 13.2 MPa, and the tensile strength is 17.8 MPa;

[0078] The Abaqus software was used to conduct tensile tests on the same transition interface of the models of the continuously gradient-structured polymer fiber scaffold and the directly stacked scaffold to observe whether the stress distribution was uniform. The results are as Figure 5 shown. It can be seen from the figure that, compared with the directly stacked structure, the stress distribution in the tensile direction of the continuous gradient transition method is more uniform, and the stress concentration phenomenon is improved;

[0079] The above-prepared continuously gradient-structured polymer fiber scaffold and the directly stacked scaffold were directly subjected to tensile tests. The results are as Figure 6 shown. It can be seen from the figure that at the same strain, the continuously gradient-structured polymer fiber scaffold has a higher tensile strength (UTS) or yield strength and a larger elastic modulus, which is beneficial to bearing greater loads.

Claims

1. A method for preparing a polymer fiber scaffold with continuously gradient structure by melt electrospinning writing, characterized in that It includes the following steps: Step 1: Design a basic homogeneous pattern based on the transitional interface characteristics of the tissue to be repaired and discretize it into a dense and ordered point sequence: ; Step 2: Design the non-linear transformation functions f and g according to the structural change characteristics at the transition interface. Use the non-linear transformation functions f and g to map the points of R one by one into one by one as , where , , i is the point serial number, so as to obtain the point sequence ; Step 3: Point sequence After equidistant sampling, the expected printing path is obtained ; Step 4: Based on the expected printing path, perform melt electrospinning direct writing to obtain a polymer fiber scaffold with continuously varying structure.

2. The melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold according to claim 1, characterized in that, In Step 1, the basic homogeneous pattern is a continuous closed line that can be completed in one stroke; the distance between adjacent points in the densely ordered point array is less than 0.1 μm.

3. The melt electrospinning direct writing preparation method of a polymer fiber scaffold with continuously gradually changing structure according to claim 1, characterized in that, In Step 1, if the transition interface of the tissue to be repaired is a ligament-bone interface or a tendon-bone interface, the basic homogeneous pattern is a 0 / 90° type grid with a grid side length of 0.02 - 2 mm; if the transition interface of the tissue to be repaired is a heart valve, the basic homogeneous pattern is a honeycomb type grid or a rhombic grid with a grid side length of 0.05 - 2 mm.

4. The melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold according to claim 1, characterized in that, In step 2, the nonlinear transformation functions f and g satisfy the Jacobian which holds for any point sequence in the basic homogeneous pattern R.

5. The melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold according to claim 1, characterized in that, In Step 3, the sampling distance is 10 - 200 μm.

6. The melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold according to claim 1, characterized in that The specific process of Step 4 is as follows: Select appropriate jet lag length values and jet deposition rates, generate the actual movement trajectory and movement rate of the X-Y moving platform based on the expected printing path and curve printing theory, and execute the printing process, including the following steps: Step a: Calculate the jet deposition rate according to the expected fiber diameter and monitor the current jet lag length value l in real time, where is the melt flow rate; is the melt flow rate Step b: Adjust the process parameters to control the jet lag length within the range of 1 - 3 mm in the stable printing state of the electrospinning direct writing system, and continuously adjust the printing path according to the monitored jet lag length l; Step c: Generate the actual motion trajectory of the X-Y moving platform according to the curve printing theory under steady state and the motion speed and input it into the motion platform controller of the electrostatic direct writing system to perform the printing process.

7. The melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold according to claim 6, characterized in that, The fiber diameter in step a is 5 to 50 μm.

8. The melt electrospinning direct writing preparation method of a structurally continuously gradient polymer fiber scaffold according to claim 6, characterized in that, The actual movement trajectory of the X-Y moving platform in step c and the movement speed are calculated through formulas (1) to (4); （1）； （2）； （3）； （4）； Among them, represents a differential operation, and i is the point number.

9. The melt electrospinning direct writing preparation method of a polymer fiber scaffold with continuously gradually changing structure according to claim 1, characterized in that The material of the polymer fiber scaffold is polycaprolactone, polylactic acid or poly(lactic-co-glycolic acid).

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