Shape memory polymer fiber membrane and preparation method thereof, shape memory polymer stent and preparation method and application thereof

Abstract

The present application relates to the field of biological tissue engineering, and discloses a shape memory polymer fiber membrane, a preparation method thereof, a shape memory polymer stent, a preparation method and application thereof. The polymer fiber membrane is composed of core-shell structure fibers, the fiber shell layer is selected from any one or more of thermoplastic polyurethane, hydrogenated styrene-butadiene block copolymer, ethylene-vinyl acetate copolymer and polyolefin elastomer, serving as a shape memory fixed phase, and the fiber core layer is a polymer with a glass transition temperature of 25-37 DEG C, serving as a shape memory reversible phase. The shape memory polymer fiber membrane is prepared by coaxial electrospinning, the shape memory polymer stent is formed by rolling and adhering the fiber membrane and loaded with basic fibroblast growth factor. The stent can be implanted minimally invasively, and the shape recovery is triggered by body temperature, and the stent is used for urethral defect treatment.

Description

Technical Field

[0001] This invention relates to the field of biological tissue engineering, specifically to a shape memory polymer fiber membrane and its preparation method, a shape memory polymer scaffold and its preparation method, and its applications. Background Technology

[0002] Urethral defects are a common clinical condition in urology. This condition can directly lead to urethral stenosis or interruption, causing complications such as difficulty urinating, urinary retention, and recurrent urinary tract infections, which seriously affect the patient's quality of life and may even lead to kidney damage. Clinically, repair methods are needed to restore the normal anatomical structure of the urethra and urinary function.

[0003] Currently, clinical treatments for urethral defects mainly include surgical repair and stent implantation. Traditional treatments primarily involve surgical repair methods such as urethral anastomosis and autologous flap transplantation. These surgeries require large incisions to expose the urethral defect, resulting in significant trauma to the patient and a long postoperative recovery period. Furthermore, for long urethral defects, autologous tissue transplantation is prone to problems such as donor site damage and transplanted tissue necrosis, with a postoperative anastomotic stenosis rate as high as 30%-50%, making it difficult to guarantee the repair outcome. To reduce surgical trauma, stent implantation is gradually being used clinically to replace some surgical treatments.

[0004] Existing stents are mainly divided into metal stents and ordinary polymer stents: Metal stents, such as nickel-titanium alloy stents, have good mechanical support and shape memory properties, but poor biocompatibility. Long-term implantation can easily cause urethral mucosal irritation and stent surface stone formation, and requires a second surgery for removal, increasing patient pain and infection risk. Ordinary polymer stents, such as polylactic acid and polycaprolactone stents, are absorbable materials, avoiding a second surgery, but lack precise shape memory function. They require a large-diameter delivery device for implantation, making minimally invasive implantation impossible. Moreover, the stent shape is fixed and cannot adapt to the different urethral anatomy dimensions of different patients, making it prone to displacement and slippage, leading to repair failure.

[0005] In recent years, a small number of shape memory scaffolds for urethral repair have emerged. However, the synergy between the fixed phase and the reversible phase of existing shape memory polymer scaffolds is poor, making it difficult to meet the extremely high shape memory performance requirements of shape memory materials for urethral repair.

[0006] Therefore, there is an urgent need to develop a novel shape memory polymer fiber with excellent shape memory properties and the polymer repair scaffold prepared therefrom. Summary of the Invention

[0007] The primary objective of this invention is to provide a shape memory polymer fiber membrane and its preparation method, a shape memory polymer scaffold and its preparation method, and its application. The polymer fiber membrane has a continuous core-shell structure, which enables full-domain synergy between the fixed phase and the reversible phase, greatly improving the shape memory performance of the material, and is particularly suitable for urethral defect treatment scenarios.

[0008] To achieve the above objectives, the present invention provides the following technical solution: A shape memory polymer fiber membrane, the fiber membrane being formed of core-shell structured fibers, the core-shell structured fibers comprising a continuous fiber shell layer and a continuous fiber core layer enclosing the interior of the fiber shell layer; The fiber shell is made of a polymeric elastomer, which serves as a shape memory stationary phase. The polymeric elastomer of the fiber shell is selected from any one or more of thermoplastic polyurethane, hydrogenated styrene-butadiene block copolymer, ethylene-vinyl acetate copolymer, and polyolefin elastomer. The fiber core layer is made of a glass transition polymer, serving as a reversible shape memory phase. The glass transition temperature of the polymer in the fiber core layer is 25°C to 37°C. The fiber core layer is used to achieve temporary shape fixation and body temperature-triggered recovery. The temperature range of 25°C to 37°C covers room temperature to human body temperature, ensuring that the fiber membrane can be molded into a temporary small-diameter shape at room temperature for convenient minimally invasive delivery. After implantation, it can automatically recover to the target shape at body temperature.

[0009] For shape memory materials, their shape memory performance is highly dependent on the synergistic effect of the stationary polymer and the reversible polymer. For example, discontinuous reversible phases are difficult to activate shape recovery synchronously under the stimulation of the target temperature, and are prone to local recovery lag or incomplete recovery; discontinuous stationary phases cannot uniformly store deformation elastic energy, causing the material's recovered shape to easily collapse locally, making it difficult to maintain a stable structure. Therefore, this invention uses polymer materials as both the stationary and reversible phases, and combines them with the preparation method described below to construct a continuously distributed reversible and stationary phase, thereby ensuring shape memory performance.

[0010] Preferably, the polymer of the fiber core layer is polypropylene carbonate, or a blend of polylactic acid and polyethylene glycol.

[0011] Polypropylene carbonate (PPC) possesses excellent biodegradability and a suitable glass transition temperature (approximately 30°C), allowing it to naturally adapt to a temperature range of 25°C to 37°C. Furthermore, its degradation products are non-toxic, preventing foreign body reactions after implantation. Blends of polylactic acid (PLA) and polyethylene glycol (PEG) utilize the plasticizing effect of PEG on PLA to adjust PLA's originally high glass transition temperature (approximately 60°C) to the 25°C to 37°C range, while retaining PLA's biocompatibility and mechanical properties.

[0012] Preferably, the thickness ratio of the fiber shell layer to the fiber core layer satisfies 85:15 to 15:85.

[0013] When the proportion of the fibrous shell layer is higher, the scaffold recovers its shape faster and more effectively, shortening the time it takes to return to the target shape after implantation. When the proportion of the fibrous core layer is higher, the scaffold has stronger shape fixation capabilities and greater stability in maintaining temporary deformations. Through an adjustable proportion design, the performance of the fibrous membrane can be flexibly adjusted according to actual needs.

[0014] Preferably, the Shore hardness of the material of the fiber shell is in the range of 58A to 85A.

[0015] The hardness range of 58A to 85A ensures that the fiber shell has a certain degree of flexibility and sufficient structural strength, so that it will not cause mechanical irritation when it adheres to the mucous membrane of biological tissues, and can maintain its original shape after the scaffold recovers.

[0016] Preferably, the number-average molecular weight of the polypropylene carbonate is in the range of 50,000 to 400,000; and the number-average molecular weight of the polylactic acid is in the range of 80,000 to 180,000.

[0017] The molecular weight range of polypropylene carbonate ensures it possesses basic mechanical strength, preventing breakage during stent deformation. This range also effectively controls its degradation rate, preventing slow degradation due to excessively high molecular weight and the resulting long-term foreign body reaction. The lower molecular weight limit of polylactic acid ensures it maintains certain mechanical properties after blending with polyethylene glycol, preventing the blended material from becoming too soft. The upper molecular weight limit prevents excessively long degradation cycles, ensuring the stent degrades promptly after urethral repair, eliminating the need for a second surgery.

[0018] Preferably, the thickness of the fiber membrane is 10~100μm.

[0019] This thickness range ensures that the fibrous membrane has sufficient strength to prevent rupture during the rolling process; at the same time, it prevents the fibrous membrane from being too thick, which could affect subsequent biological tissue therapy applications.

[0020] The present invention also provides a method for preparing the shape memory polymer fiber membrane, which includes the following steps: S1: Preparation of electrospinning solution Preparation of fiber shell solution: The polymer of the fiber shell is dissolved in the fiber shell solvent to prepare a fiber shell solution; preferably, when the fiber shell material is thermoplastic polyurethane, the fiber shell solvent is tetrahydrofuran; Preparation of fiber core layer solution: The polymer of the fiber core layer is dissolved in the fiber core layer solvent to prepare a fiber core layer solution; preferably, when the fiber core layer material is polypropylene carbonate, the fiber core layer solvent is acetone; when the fiber core layer material is a blend of polylactic acid and polyethylene glycol, the fiber core layer solvent is tetrahydrofuran.

[0021] S2: Coaxial electrospinning to prepare fiber membranes Under conditions of room temperature and humidity of 45%-50%, the fiber shell solution and fiber core solution are injected into the outer and inner injectors of the coaxial electrospinning device, respectively, to perform coaxial electrospinning and obtain a fiber membrane composed of core-shell structured fibers.

[0022] Preferably, the concentrations of both the fiber shell solution and the fiber core solution are 0.06-0.10 g / mL.

[0023] When the spinning solution concentration is too low, the polymer chains are insufficiently entangled, and the solution viscosity is too low, leading to beaded fibers, discontinuous droplets, and other issues. The resulting fibers are discontinuous and have uneven diameters. Conversely, when the spinning solution concentration is too high, the polymer chains are excessively entangled, resulting in poor fluidity. The solution viscosity is too high, leading to needle blockage, difficulty in stretching, and difficulty in solvent evaporation. The resulting fibers are continuous but have excessively large diameters and rough surfaces. The ideal concentration range allows the polymer chains to have sufficient entanglement to form continuous fibers while maintaining sufficient fluidity to be fully stretched by the electric field, thereby obtaining ideal nanofibers with uniform diameters and smooth surfaces.

[0024] Preferably, the spinning voltage is 10-20 kV and the distance from the nozzle to the receiving device is 12-18 cm.

[0025] The present invention also provides a shape memory polymer scaffold made using the above-mentioned shape memory polymer fiber membrane.

[0026] The shape memory polymer scaffold is formed by curling and bonding the shape memory polymer fiber membrane; the diameter of the scaffold is 5-8 mm, which covers the common size of the adult urethral lumen, and can be adapted to the urethral diameter of different patients by selecting fiber membranes of different thicknesses or adjusting the number of curling layers; and the scaffold is also loaded with basic fibroblast growth factor, which can significantly promote the proliferation of urethral mucosal epithelial cells and the formation of new blood vessels.

[0027] The present invention also provides a method for preparing the shape memory polymer scaffold, which includes the following steps: Step 1: Curl The fiber membrane is rolled on a polytetrafluoroethylene (PTFE) core rod. The PTFE material has a smooth surface, which can prevent the fiber membrane from sticking to the core rod. The number of rolled layers is determined according to the diameter of the target scaffold and the thickness of the fiber membrane. Step 2: Heating and bonding After fixing the ends of the fiber membrane with high-temperature adhesive tape, the rolled fiber membrane and the core rod are placed together in an oven and isothermally treated at 180°C for 5 minutes to melt the thermoplastic polyurethane of the fiber shell and achieve inter-fiber adhesion. 180°C is the melting temperature of the thermoplastic polyurethane of the fiber shell, which can achieve tight adhesion between fibers and ensure the stability of the scaffold shape. After cooling, the high-temperature adhesive tape is removed and taken off from the core rod to obtain the tubular shape memory polymer scaffold body. Step 3: Loading with basic fibroblast growth factor The scaffold obtained in step two was incubated in an alkaline fibroblast growth factor solution with a concentration of 2 mg / L at 37°C for 24 h with shaking to allow the solution to fully wet the scaffold, thus obtaining the shape memory polymer fiber scaffold.

[0028] Based on the characteristics of the shape memory polymer scaffold described above, the present invention provides an application of the scaffold, namely, as a scaffold for the treatment of urethral defects.

[0029] The stent can be shaped into a small-diameter temporary form at room temperature and delivered to the defect site via a urethroscope through a minimally invasive procedure. After implantation, it automatically returns to the target diameter under body temperature stimulation, closely fitting the urethral lumen. At the same time, the loaded basic fibroblast growth factor is slowly released, accelerating mucosal repair. The material can be gradually degraded, eliminating the need for a second surgery to remove it.

[0030] Compared with the prior art, the present invention has the following advantages: (1) By constructing a core-shell structure with a continuous fiber shell and fiber core, the present invention avoids the problem of the failure of the fixed phase and the reversible phase due to the discontinuity of the core-shell structure of existing stents. The core-shell structure can effectively prevent local collapse after stent recovery and ensure the maintenance of the urethral lumen morphology.

[0031] (2) The transition temperature of the fiber core polymer provided by the present invention is controlled in the range of 25°C to 37°C. No external heating device is required. After the stent is implanted, the shape recovery can be triggered by the body temperature, which simplifies the clinical operation process and avoids thermal damage to the urethral mucosa caused by external heating.

[0032] (3) The shape memory polymer scaffold provided by the present invention is suitable for urethral repair scenarios. The scaffold size is adapted to the anatomical size of the adult urethra. At the same time, it is loaded with basic fibroblast growth factor, which can promote the proliferation of mucosal epithelial cells and the formation of new blood vessels, and shorten the repair cycle. Attached Figure Description

[0033] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0034] Figure 1 This is a schematic diagram of the preparation process of the coaxial electrospinning core-shell structure shape memory polymer fiber membrane provided in Embodiment 1 of the present invention; Figure 2 This is a flowchart illustrating the fabrication process of the shape memory polymer scaffold provided in Embodiment 3 of the present invention. Figure 3 The dynamic thermodynamic cycle performance test curve of Experimental Example 1 of this invention; Figure 4 These are confocal laser scanning microscope images of human umbilical vein endothelial cells cultured for 1 day and 3 days in the control group and the scaffold group of Example 3 of the present invention, showing staining. Detailed Implementation

[0035] To further understand the present invention, preferred embodiments of the present invention will be described below in conjunction with the accompanying drawings and examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, and are not intended to limit the scope of the claims of the present invention.

[0036] Example 1 This embodiment provides a shape memory polymer fiber membrane and its preparation method.

[0037] The method for preparing the shape memory polymer fiber membrane in this embodiment is as follows: Figure 1 As shown, the specific steps include: S1: Preparation of electrospinning solution Preparation of fiber shell solution: Weigh 2.0g of biocompatible thermoplastic polyurethane powder and add it to 25mL of tetrahydrofuran. Stir magnetically in a water bath at 35℃ for 3h until completely dissolved to form a uniform and transparent solution with a concentration of 0.08g / mL. Let stand for 30min to remove bubbles to avoid spinning bubbles.

[0038] Preparation of fiber core layer solution: Weigh 1.75g ​​of polypropylene carbonate particles and add them to 25mL of acetone. Stir magnetically at room temperature for 4h until completely dissolved to form a homogeneous solution with a concentration of 0.07g / mL. Let it stand for 30min to remove bubbles and ensure that the solution is free of impurities that may affect the spinning quality. The glass transition temperature of biocompatible thermal polypropylene carbonate was determined to be 32℃ by differential scanning calorimetry.

[0039] S2: Coaxial electrospinning to prepare fiber membranes The spinning environment was set to room temperature and 48% relative humidity. The shell solution was injected into the outer tube injector of the coaxial spinning device, and the core solution was injected into the inner tube injector. The ratio of the two injector feed rates was adjusted to 3:1, so that the thickness ratio of the fiber shell to the core layer was 70:30. The high-voltage power supply was turned on and the spinning voltage was set to 16kV, the receiving roller speed to 80r / min, and the distance between the nozzle and the receiving roller to 15cm. Spinning was continued for 4 hours. A shape memory polymer fiber membrane with continuous distribution of both the fiber shell and the fiber core layer was obtained in this embodiment.

[0040] After spinning, the fiber membrane prepared in this embodiment was transferred to a vacuum drying oven at 25°C and dried for 24 hours to remove residual solvent.

[0041] Example 2 This embodiment also provides a shape memory polymer fiber membrane and its preparation method.

[0042] The difference between the preparation method in this embodiment and that in Example 1 is that the solvent for the fiber core layer is replaced with a blend of polylactic acid and polyethylene glycol instead of polypropylene carbonate. Specifically, when preparing the fiber core layer solution, a blend of polylactic acid and polyethylene glycol is selected, wherein the polylactic acid has a number-average molecular weight of 120,000, and the polyethylene glycol has a molecular weight of 4,000, and the two are mixed at a mass ratio of 8:2. The glass transition temperature of this blend is 28°C, as determined by differential scanning calorimetry.

[0043] Example 3 This embodiment provides a shape memory polymer scaffold and its preparation method. The shape memory polymer scaffold is formed by rolling and bonding the shape memory polymer fiber membrane of Example 1, and basic fibroblast growth factor is also attached to it.

[0044] like Figure 2 As shown, the method for preparing the shape memory polymer scaffold in this embodiment includes the following steps: Step 1: Curl The shape memory polymer fiber membrane prepared in Example 1 was laid flat on the surface of a polytetrafluoroethylene mandrel (4 mm in diameter), and then rolled gently on the mandrel. A total of 20 layers were rolled, and the total thickness obtained by rolling was 6 mm.

[0045] Step 2: Heating and bonding After fixing the ends of the fiber membrane with high-temperature adhesive tape, the rolled fiber membrane and the core rod are placed in an oven and isothermally treated at 180°C for 5 minutes to melt the thermoplastic polyurethane in the fiber shell, achieving adhesion between the fibers and connecting the rolled fiber membrane into a whole structure. Then, the oven is closed, and after the temperature cools naturally to room temperature, the high-temperature adhesive tape is carefully removed, and the support body is removed from the polytetrafluoroethylene core rod.

[0046] Step 3: Loading with basic fibroblast growth factor First, weigh 0.02 mg of basic fibroblast growth factor powder and dissolve it in 10 mL of phosphate buffer. Use a pipette to repeatedly pipette until completely dissolved, ensuring a uniform concentration, to obtain a 2 mg / L basic fibroblast growth factor solution. Then, immerse the scaffold obtained in step two in this solution and place it in a constant-temperature shaker at 37°C and 110 rpm for 24 hours to allow the solution to fully wet the pores inside the scaffold and allow the basic fibroblast growth factor to be uniformly adsorbed onto the fiber surface. After incubation, remove the scaffold and allow it to air dry naturally in a sterile laminar flow hood to obtain a shape memory polymer scaffold.

[0047] Example 4 This embodiment is based on the preparation method of Example 3 and provides another shape memory polymer scaffold, the difference being that the shape memory polymer fiber membrane in Example 3 is replaced with the shape memory polymer fiber membrane in Example 2.

[0048] Furthermore, since the fiber core materials used in Examples 1 and 2 are different, the thickness of the shape memory polymer fiber membranes prepared by them is different. Therefore, in step one, the number of curled layers is changed to 19 layers, and the remaining steps and conditions are the same as in Example 3, resulting in another shape memory polymer scaffold that is different from that in Example 3, with a thickness of 5.94 mm.

[0049] Experimental Example 1: Shape Memory Performance This experimental example is based on the shape memory polymer scaffold prepared in Example 3. Its shape memory performance is verified through a specific testing procedure, and its shape memory performance is evaluated through dynamic thermodynamic cycling test. The scaffold's "deformation-fixation-recovery" ability under body temperature stimulation is verified.

[0050] The testing method is as follows: A TA Instruments Q800 dynamic thermomechanical analyzer was used, employing tensile mode. Fiber membranes were cut from the same batch of stents prepared in Example 3 and processed into standard samples with dimensions of 40 mm in length, 5 mm in width, and 0.5 mm in thickness. Three parallel samples were set up for each group. Before testing, the samples were sterilized with 75% ethanol for 2 hours, washed three times with PBS, and equilibrated at 25°C and 45% humidity for 24 hours. The testing procedure simulated a clinical application scenario for the stent, with a cycle of "high-temperature deformation - cooling and fixation - low-temperature unloading - high-temperature recovery." In the initial stage (0~5min), the temperature is raised to 37℃ as quickly as possible and held for 5min to allow the fiber core layer to enter a highly elastic state; During the high-temperature deformation stage (5~6.5 min), the specimen is stretched under a constant stress of 0.8 MPa at a constant temperature of 37℃ to cause the specimen to deform and elongate. During the cooling and fixing stage (6.5~18min), while keeping the load constant, the temperature is reduced to 25℃ as quickly as possible and held for 5min to fix the temporary shape. During the unloading and shaping stage (18-20 min), the load was removed, and the shape was stabilized at room temperature for 2 min. The residual strain of the temporary shape was recorded. During the second heating recovery stage (20~45min), the temperature was raised to 37℃ as quickly as possible, followed by isothermal treatment, and the shape recovery process was monitored.

[0051] Test results are as follows Figure 3 As shown, the red curve represents strain (unit: %, corresponding to the left vertical axis), reflecting the change in the degree of deformation of the stent; the blue curve represents temperature (unit: °C, corresponding to the right upper vertical axis), reflecting the temperature control process of the test environment; and the black curve represents stress (unit: MPa, corresponding to the right lower vertical axis), reflecting the stress response of the stent during deformation.

[0052] The specific results are as follows: In the initial stage, the blue temperature curve stabilized after rising to 37℃, the red strain curve maintained the baseline (≈0%), and the black stress curve was 0, indicating that the stent was in a stable, highly elastic state in its initial shape. In the high-temperature deformation stage, the black stress curve rose to 0.8MPa, the red strain curve gradually rose to 42.5% under stress, and the blue temperature curve remained at 37℃, showing that the fiber shell and core layer underwent elastic deformation, generating elastic energy. In the cooling and fixing stage, the black stress curve remained stable at 0.8MPa, the blue temperature curve dropped to 25℃, the fiber core layer returned to the glassy state, and the red strain curve stabilized at 42.5%. After low-temperature unloading, the red strain curve only slightly decreased to 39.5%, and the calculated shape fixation rate was 93%, indicating that the stent had excellent temporary shape retention capability and stored most of the elastic energy. During the high-temperature recovery phase, when the blue temperature curve rises to 37°C, the fiber core layer re-enters a highly elastic state, and the stored elastic energy is released to drive shape recovery. The red strain curve gradually decreases to 2.1%, and the calculated shape recovery rate is 95%, verifying that the stent can efficiently recover to its initial shape under body temperature stimulation.

[0053] In summary, the stent demonstrated a 93% shape fixation rate and a 95% shape recovery rate through dynamic thermodynamic cycle testing, proving that it can meet the clinical requirement of "room temperature compression fixation - in vivo temperature recovery expansion," providing direct performance evidence for minimally invasive implantation and reliable support in the treatment of urethral defects.

[0054] Experimental Example 2: Cell Compatibility This experiment focuses on the shape memory polymer scaffold prepared in Example 3. In vitro cell compatibility testing was conducted using human umbilical vein endothelial cells (HUVECs) as a model to verify the scaffold's biocompatibility. The experimental procedure is as follows: Cells were cultured in a 37°C, 5% CO2 incubator on modified Eagle Medium (Gibco) containing 10% fetal bovine serum (Gibco) and 1% penicillin-streptomycin solution. Cell proliferation was then assessed by dispersing HUVECs onto the surface of the samples. Prior to the experiment, all samples were sterilized overnight with 75% ethanol and then washed with phosphate-buffered saline (PBS). The sterilized specimens were placed in 96-well plates and then cultured at 1 × 10⁻⁶ wells. 5 1 mL of HUVECs were seeded at a density of cells / mL. Cells were incubated at 37°C for 1 day and 3 days, respectively. Then, the culture medium was removed, and 500 μL of fresh culture medium containing 100 μL / mL (5 mg) of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazole bromide (MTT) solution was added, and the cells were incubated at 37°C for an additional 4 hours. After carefully removing the culture medium, 400 μL of dimethyl sulfoxide (DMSO) was added to form a purple solution. After shaking for 5 minutes, 200 μL of the purple solution was filled into 96-well plates, and the absorbance at 570 nm was measured using a Varioscan Flash microplate reader (Thermo Fisher Scientific). To study the morphology of cell proliferation on the samples, HUVECs incubated for 3 days were stained with calcein AM (A017, USA) for 20 minutes, followed by gentle washing twice with PBS. Cell attachment and diffusion on the specimen were observed using a confocal laser scanning microscope (CLSMTCSSP5, Leica, Germany).

[0055] Cell morphology observation results as follows Figure 4 As shown, this figure contains the survival / death ratio staining results of the control group (without scaffold) and the test group (scaffold group of Example 3) at 1 day (Day 1) and 3 days (Day 3) of culture. The scale bar of all images is 50 μm. At 1 day of culture, scattered live cells (showing green fluorescence) can be seen in both the control group and the test group. The cell morphology is mainly round or short spindle-shaped. There is no significant difference in the number of cells in the test group compared with the control group, indicating that the initial contact of the scaffold with the cells did not affect cell attachment. At 3 days of culture, the cells in both groups have proliferated significantly and spread sufficiently. The cell morphology has changed to long spindle-shaped or polygonal, and the pseudopodia of the cells have been clearly extended. Among them, the HUVECs in the test group can be uniformly attached to the surface of the scaffold fibers, and even form a continuous cell layer along the scaffold structure. There is no significant difference in cell diffusion status compared with the control group. This directly proves that the scaffold surface has good cell affinity and can support the normal morphological development and diffusion of HUVECs.

[0056] The test results of this experiment show that the shape memory polymer scaffold prepared in Example 3 supports the normal proliferation, attachment and diffusion of vascular endothelial cells and has excellent cell compatibility, providing key biocompatibility evidence for its possible subsequent in vivo implantation application.

[0057] Therefore, combining the structural fabrication and functional loading processes of the preceding embodiments, and the key performance verification results of each experimental example, the shape memory polymer scaffold provided by this invention can be used as a tool for the treatment of urethral defects, as detailed below: First, the core-shell structure of the stent is achieved through coaxial electrospinning, ensuring a continuous distribution of both the fiber shell (the stationary phase) and the fiber core (the reversible phase). The glass transition temperature of the fiber core material is in the range of 25–37°C, allowing for shape recovery triggered by body temperature without the need for external heating. Dynamic thermodynamic cycling tests in Example 1 show that the stent achieves a shape fixation rate of 93% and a shape recovery rate of 95%. It can stably maintain a small-diameter shape suitable for minimally invasive delivery channels at room temperature, accurately recovering to the target diameter after implantation, effectively avoiding mechanical damage to the urethral mucosa. Its structural and performance characteristics are highly compatible with the technical requirements of urethral implantation scenarios. Secondly, the stents prepared in Examples 3-4 all have a diameter of about 6 mm, which covers the common size range of 5-8 mm for adult urethral lumen. Furthermore, the number of layers of the fibrous membrane can be adjusted to accommodate the anatomical differences of different patients' urethras. At the same time, basic fibroblast growth factor is loaded during the stent preparation process using a constant temperature shaker incubation process. This bioactive factor can be slowly released after the stent is implanted in the body, which can promote angiogenesis and proliferation of mucosal epithelial cells in the urethral defect area. This overcomes the technical deficiency of traditional urethral stents, which can only provide mechanical support and cannot actively promote tissue repair. Its size design and functional load are specifically designed to meet the clinical needs of urethral defect treatment. Finally, the cell compatibility test results of Experiment 2 showed that the scaffold surface can support the normal attachment, proliferation and morphological differentiation of human umbilical vein endothelial cells. After 3 days of culture, the cells can form a continuous cell layer without toxic reaction, proving that the scaffold has excellent biocompatibility. In addition, the fibrous membrane material used in the scaffold is polypropylene carbonate or polylactic acid-polyethylene glycol blend, both of which have good biodegradability and can degrade naturally after urethral repair, without the need for a second surgery to remove it, which meets the biosafety requirements of implantable devices.

[0058] Based on this, the shape memory polymer scaffold of the present invention matches the clinical needs of urethral defect treatment in terms of structural design, performance parameters, functional configuration and biosafety, and can be used as a dedicated scaffold for the treatment of urethral defects.

[0059] In practical applications, the stent can be placed in 37°C saline solution for 5 minutes to allow the fibrous core to reversibly enter a highly elastic state, enhancing its flexibility. It is then compressed to 3mm to fit the minimally invasive channel and cooled to room temperature for 5 minutes to fix its temporary shape. After pretreatment, the stent is implanted into the defect site via the urethra. Body temperature triggers the fibrous core to revert to its highly elastic state, and the fibrous shell releases elastic energy, driving the stent to spontaneously expand to its initial diameter and conform to the urethral wall. This provides mechanical support for the urethral defect, preventing luminal stenosis or collapse and providing a stable three-dimensional environment for repair. Simultaneously, the basic fibroblast growth factor loaded on the stent is slowly released over time, promoting angiogenesis in the urethral defect area, improving local blood supply, providing nutrition to damaged tissue, and accelerating epithelial cell proliferation and stromal regeneration. In summary, the shape memory polymer scaffold of this invention activates the endogenous repair mechanism of tissues through the synergistic effect of mechanical support and active repair promotion, which can significantly improve the effectiveness and functionality of urethral defect treatment. Its structural design, performance parameters, functional configuration and biosafety are highly matched with the clinical needs of urethral defect treatment, and it can be used as a dedicated scaffold for urethral defect treatment.

[0060] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of a shape memory polymer fiber membrane in the preparation of a shape memory polymer urethral stent, characterized in that, The fiber membrane is formed of core-shell structured fibers, which include a continuous fiber shell and a continuous fiber core enclosing the inside of the fiber shell. The method for preparing the fiber membrane includes the following steps: S1: Preparation of electrospinning solution Preparation of fiber shell solution: The polymer of the fiber shell is dissolved in a fiber shell solvent to prepare a fiber shell solution; the polymer of the fiber shell is polyurethane, and the fiber shell solvent is tetrahydrofuran; Preparation of fiber core layer solution: The polymer of the fiber core layer is dissolved in a fiber core layer solvent to prepare a fiber core layer solution; the polymer of the fiber core layer is polypropylene carbonate, or a blend of polylactic acid and polyethylene glycol; The polypropylene carbonate has a number average molecular weight of 50,000 to 400,000; in the blend of polylactic acid and polyethylene glycol, the number average molecular weight of polylactic acid is 120,000 and the number average molecular weight of polyethylene glycol is 4,000, and the two are mixed at a mass ratio of 8:

2. S2: Coaxial electrospinning to prepare fiber membranes Under room temperature and humidity of 45-50%, the fiber shell solution and the fiber core solution are injected into the outer and inner injectors of the coaxial electrospinning device, respectively. The ratio of the feed rate of the outer and inner injectors is adjusted to 3:1, so that the thickness ratio of the fiber shell to the core layer is 70:

30. The spinning voltage is set to 16kV, the receiving roller speed is 80r / min, and the distance between the nozzle and the receiving roller is 15cm. Coaxial electrospinning is performed to obtain the fiber membrane. The method for preparing the shape memory polymer urethral stent includes the following steps: Step 1: Curl The fiber membrane is rolled up on a polytetrafluoroethylene core rod, and the number of rolled layers is determined according to the diameter of the target scaffold and the thickness of the fiber membrane. Step 2: Heating and bonding After fixing the fiber membrane ends with high-temperature adhesive tape, the rolled fiber membrane and the core rod are placed in an oven and isothermally treated at 180°C for 5 minutes to melt the fiber shell and achieve inter-fiber adhesion. After cooling, the high-temperature adhesive tape is removed and the core rod is taken off to obtain a tubular shape memory polymer urethral stent body. Step 3: Loading with basic fibroblast growth factor Basic fibroblast growth factor powder is dissolved in phosphate buffer to obtain basic fibroblast growth factor solution; then the scaffold body obtained in step two is immersed in basic fibroblast growth factor solution to obtain the shape memory polymer urethral stent.

2. The application of the shape memory polymer fiber membrane according to claim 1 in the preparation of a shape memory polymer urethral stent, characterized in that, The thickness of the fiber membrane is 10~100μm.

3. The application of the shape memory polymer fiber membrane according to claim 1 in the preparation of a shape memory polymer urethral stent, characterized in that, The diameter of the bracket is 5~8mm.

4. The application of the shape memory polymer urethral stent according to claim 1, characterized in that, Shape memory polymer urethral stents used to treat urethral defects.

Images