A biodegradable esophageal stent and a preparation method thereof

Abstract

This invention relates to the field of medical materials technology, and discloses a biodegradable esophageal stent and its preparation method. The esophageal stent is woven from blended monofilaments. The raw materials for the blended monofilaments include polylactic acid, polycaprolactone, and additives, including polyethylene glycol, carbon nanofibers, star-shaped PLA-PCL block copolymer, and talc. The preparation steps are as follows: the raw materials are mixed in proportion, melt-blended and granulated, and then the blended monofilaments are obtained using a high-pressure capillary rheometer; the blended monofilaments are woven into a mesh-like stent framework on a mold using an interlaced pressing method, then heat-set, and demolded after cooling; a thermoplastic polyurethane casting liquid loaded with bioactive substances is cast into a film and coated onto the inner wall of the stent framework; the thermoplastic polyurethane film is heated to fuse with the stent framework, and after cooling, the esophageal stent is formed. The esophageal stent of this invention has good mechanical properties, controllable degradation characteristics, and biocompatibility.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, and in particular relates to a biodegradable esophageal stent and its preparation method. Background Technology

[0002] Esophageal stricture, esophageal fistula, and other diseases severely reduce patients' quality of life. Esophageal stent placement is an effective means of relieving dysphagia, but existing technologies (mainly metal stents and some plastic stents) have many drawbacks: 1. Metal stents are usually made of nickel-titanium alloy or stainless steel wire woven into a mesh-like cylindrical structure, utilizing their superelasticity or shape memory function to achieve self-expansion. Some products are coated with silicone or polyurethane films to prevent tissue ingrowth. However, as permanent implants, metal stents are difficult to remove even after expansion, requiring a second endoscopic surgery, causing secondary trauma and pain to the patient. 2. Plastic stents are usually made of polyester (such as PET) or silicone, forming a solid-walled tubular structure that requires mechanical expansion using tools such as balloons. Their walls are thicker and more rigid, with far less flexibility than metal braided stents, making it difficult to adapt to the physiological curvature of the esophagus, resulting in a strong foreign body sensation and poor patient comfort. It is prone to displacement and has poor adhesion to the esophageal wall, making it extremely easy for the stent to migrate and resulting in a high rate of dislodgement, which can lead to treatment failure. The implantation procedure is complex, usually requiring a large diameter stent that needs to be pre-dilated before implantation, which increases the complexity and risk of the surgery.

[0003] First-generation biodegradable esophageal stents primarily utilize single biodegradable materials, such as pure polylactic acid (PLA) or polycaprolactone (PCL), fabricated through laser cutting or weaving methods. For example, the ELLA-BD stent (made of pure PLA) exhibits this characteristic. However, due to the inherent properties of PLA and PCL, a contradiction exists between their mechanical and degradation performance: pure PLA stents are excessively rigid, brittle, and lack flexibility, making them prone to breakage or pressure damage to the esophageal wall in the constantly moving environment of the esophagus; pure PCL stents, on the other hand, have insufficient strength and degrade too slowly, failing to provide adequate radial support to maintain luminal patency. Furthermore, their degradation cycle of several years does not match the treatment window of several weeks to months for esophageal diseases.

[0004] Therefore, metal and plastic stents cause long-term complications due to their non-degradability; while early biodegradable stents, due to their limited material options, could not simultaneously achieve the required mechanical properties and biodegradability. Existing technologies have failed to adequately address the balance between support, flexibility, and degradation rate. Summary of the Invention

[0005] In view of this, the purpose of this invention is to provide a biodegradable esophageal stent and its preparation method, which has good mechanical properties, controllable degradation characteristics and biocompatibility.

[0006] The present invention solves the above-mentioned technical problems through the following technical means:

[0007] In a first aspect, the present invention discloses a biodegradable esophageal stent, wherein the esophageal stent is woven from blended monofilaments, the raw materials of which include polylactic acid, polycaprolactone and additives, wherein the additives include polyethylene glycol, carbon nanofibers, star-shaped network PLA-PCL block copolymers and talc.

[0008] In this technical solution, a blend of polylactic acid (PLA) and polycaprolactone (PCL) is used as the matrix; PLA provides rigidity, support, and a relatively fast degradation rate, while PCL provides flexibility and long-term plasticity. A preliminary balance between mechanical properties and degradation cycle can be achieved by adjusting the ratio of the two.

[0009] Carbon nanofibers, acting as a reinforcing agent, are uniformly dispersed in the matrix, significantly improving the tensile strength and radial support of the monofilaments and preventing the scaffold from collapsing under the long-term pressure of esophageal peristalsis. Polyethylene glycol, acting as a plasticizer and hydrophilic agent, improves the material's processing flowability, reduces brittleness, and enhances the surface hydrophilicity of the monofilaments, reducing friction on esophageal tissue. Talc, acting as a nucleating agent, promotes PLA crystallization, improving the heat resistance and dimensional stability of the monofilaments.

[0010] The star-shaped PLA-PCL block copolymer acts as a molecular bridge in the system; its PLA segments are thermodynamically compatible with the PLA homopolymer phase region, while the PCL segments are compatible with the PCL phase region. Due to its star-shaped structure, individual molecules can be simultaneously and firmly anchored in two incompatible phase regions, thus strongly inhibiting phase separation. Furthermore, its network structure itself possesses a three-dimensional network structure. During melt blending, the long-chain molecules of PLA and PCL physically interpenetrate and entangle into this pre-fabricated network. This is not merely interfacial compatibilization, but rather the construction of an interpenetrating / semi-interpenetrating network throughout the system, physically preventing the formation of large-size phase regions of PLA and PCL. This dual effect of chemical anchoring and physical entanglement far surpasses that of traditional linear block copolymer compatibilizers. It not only refines the dispersed phase size but also forms extremely strong adhesion at the phase interface, potentially significantly improving the melt strength and mechanical integrity of the entire blend.

[0011] The high-performance blended monofilaments are woven into a mesh skeleton and then heat-set. This structure achieves an optimal balance between resilience and flexibility, allowing the support to self-expand and conform to the esophagus, while also bending appropriately with esophageal peristalsis.

[0012] Furthermore, the esophageal stent is provided with a functional inner lining, which is a thermoplastic polyurethane film loaded with bioactive substances. The thermoplastic polyurethane film is attached to the inner wall surface of the esophageal stent by heating and bonding, forming a fiber-film composite structure. The fiber-membrane composite material has significantly improved strength compared to a single film material or fiber network, and the addition of the thermoplastic polyurethane film allows the esophageal stent to release drugs locally after implantation, actively inhibiting inflammation and tissue hyperplasia, thereby achieving functionalization.

[0013] Furthermore, the bioactive substance is selected from at least one of antibacterial agents or antiproliferative drugs; preferably, the antibacterial agent is silver nanoparticles, and the antiproliferative drug is rapamycin.

[0014] Furthermore, the mass ratio of polylactic acid to polycaprolactone is (1~9):1.

[0015] Furthermore, the molecular weight of the polyethylene glycol is 1,000-20,000, preferably 5,000; the added mass of the polyethylene glycol is 1%-3% of the total mass of polylactic acid and polycaprolactone.

[0016] Furthermore, the carbon nanofibers added are 1%-3% of the total mass of polylactic acid and polycaprolactone, and the talc added are 0.1%-0.3% of the total mass of polylactic acid and polycaprolactone.

[0017] Furthermore, the diameter of the blended monofilament is 0.2mm-0.35mm.

[0018] Furthermore, the esophageal stent has a diamond-shaped mesh structure, and its monofilament weaving angle α satisfies tanα°=2. Research in this invention has found that when the monofilament angle satisfies tanα°=2, the resulting stent, when combined with the inner membrane, exhibits good resilience and flexibility.

[0019] Furthermore, the star-shaped network PLA-PCL block copolymer is added at a mass of 0.2%-0.4% of the total mass of polylactic acid and polycaprolactone, and the preparation method of the star-shaped network PLA-PCL block copolymer includes the following steps:

[0020] In the absence of water and oxygen and in the presence of a catalyst, ε-caprolactone monomers are subjected to ring-opening polymerization using a multifunctional small molecule containing at least three hydroxyl groups as an initiator to obtain hydroxyl-terminated star-shaped polycaprolactone prepolymers.

[0021] Without separating the star-shaped polycaprolactone prepolymer, lactide monomer was added to the reaction system, and the ring-opening polymerization reaction was continued to obtain a hydroxyl-terminated star-shaped PCL-b-PLA block copolymer.

[0022] The terminal hydroxyl groups of the obtained star-shaped PCL-b-PLA block copolymer were reacted with a mercapto-containing compound to obtain a star-shaped PCL-b-PLA block copolymer with mercapto-terminated groups.

[0023] The star-shaped PCL-b-PLA block copolymer with thiol end groups was oxidized under controlled conditions to form dynamic disulfide bonds between some of the thiol groups, resulting in a slightly cross-linked star-shaped network PLA-PCL block copolymer.

[0024] Furthermore, the controllable oxidation conditions are as follows: at room temperature, the star-shaped PCL-b-PLA block copolymer with thiol end groups is treated with a catalytic amount of oxidant, and the degree of oxidation is controlled so that 20% to 40% of the thiol groups are oxidized to form intermolecular disulfide bonds.

[0025] Secondly, this invention discloses a method for preparing a biodegradable esophageal stent, comprising the following steps:

[0026] S1. Polylactic acid, polycaprolactone, polyethylene glycol, carbon nanofibers, star-shaped network PLA-PCL block copolymer and talc are mixed in proportion, melt-blended and granulated, and then blended monofilaments are obtained using a high-pressure capillary rheometer.

[0027] S2. The blended monofilaments obtained in step S1 are woven into a mesh-like support skeleton on a mold by interlacing and pressing, and then heat-set at 160℃~180℃, and demolded after cooling.

[0028] S3. Cast the thermoplastic polyurethane casting liquid loaded with bioactive substances into a film, or directly use a pre-made thermoplastic polyurethane film to cover the inner wall of the stent skeleton obtained in step S2, and heat it at 160℃~180℃ to fuse the thermoplastic polyurethane film with the stent skeleton. After cooling, the esophageal stent is formed.

[0029] Furthermore, in step S3, the heating method is hot pressing, hot air, or infrared irradiation.

[0030] In summary, this application has the following beneficial effects:

[0031] 1. This invention balances support and flexibility at the matrix level by blending polylactic acid (PLA) and polycaprolactone (PCL) in a specific ratio. Furthermore, this ratio is adjustable, providing a basis for customizing the degradation cycle to match the treatment window for esophageal strictures, overcoming the shortcomings of pure PLA (high brittleness) and pure PCL (low strength / slow degradation).

[0032] 2. This invention uses a star-shaped network PLA-PCL block copolymer with a specific structure as a compatibilizer. Its star-shaped arms and slightly cross-linked network structure not only strongly bridge the PLA and PCL phases like molecular anchors, preventing phase separation, but also allow long-chain PLA and PCL molecules to intercalate into the network, forming physical entanglement, greatly enhancing interfacial bonding and the overall material's toughness and mechanical integrity. The addition of carbon nanofibers as reinforcement significantly improves the tensile strength and radial support of the monofilaments, effectively preventing the scaffold from collapsing under long-term pressure. The addition of polyethylene glycol as a plasticizer improves the material's processing flowability and the flexibility of the monofilaments. The addition of talc as a nucleating agent promotes PLA crystallization, improving the heat resistance and dimensional stability of the monofilaments.

[0033] 3. This invention employs a diamond-shaped mesh weaving structure, with the weaving angle limited to tana°=2. The stent under this structure exhibits excellent radial support force (reaching over 37N) and a high resilience rate (over 90%), enabling it to reliably self-expand to conform to the esophageal wall. After cyclic compression testing, the stent maintains stable mechanical properties, demonstrating its long-term reliability. Furthermore, it ensures good flexibility, adapting to the physiological curvature of the esophagus.

[0034] 4. In this invention, a thermoplastic polyurethane film loaded with bioactive substances (such as antibacterial silver nanoparticles and antiproliferative drug rapamycin) is composited onto the inner wall of the stent by heating. This "fiber-film" composite structure not only acts as a physical barrier to prevent esophageal tissue or tumors from growing inward from the mesh, but also enables local and continuous release of drugs, actively inhibiting inflammation and excessive tissue proliferation, thereby reducing the risk of restenosis from the etiological perspective. Attached Figure Description

[0035] Figure 1 The graph shows the properties of the PLA / PCL blended fibers in Example 5.

[0036] Figure 2 The graph shows the properties of the PLA / PCL / PEG blended fibers in Example 6.

[0037] Figure 3 The diagram shows the performance of different esophageal stent structures in Example 7. Detailed Implementation

[0038] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0039] Example 1

[0040] This embodiment describes the preparation of a star-shaped network PLA-PCL block copolymer, including the following steps:

[0041] 1. In a dry Schlenk flask, add dry pentaerythritol (0.34 g, 2.5 mmol) and 20 mL of anhydrous toluene, and azeotropically remove water. After cooling, add ε-caprolactone (20.0 g, 175.4 mmol) and stannous octoate catalyst (0.081 g, 0.2 mmol), and react at 110°C under nitrogen protection for 12 hours. Then cool to 90°C, add D,L-lactide (20.0 g, 138.9 mmol), and continue the reaction for 24 hours. The reaction solution is dissolved in dichloromethane, precipitated with cold methanol, washed, and dried under vacuum to obtain a four-armed star-shaped (PCL-b-PLA)4-OH.

[0042] 2. The above product (10.0 g) was dissolved in 150 mL of dichloromethane. 3-Mercaptopropionic acid (0.85 g, 8.0 mmol), DMAP (0.49 g, 4.0 mmol), and DCC (1.65 g, 8.0 mmol) were added under ice bath conditions. After reacting at room temperature for 24 hours, the mixture was filtered. The filtrate was washed with acid, alkali, and water, dried, and then precipitated in diethyl ether to obtain (PCL-b-PLA)4-SH.

[0043] 3. Dissolve the thiolized product (5.0 g) in a DMF / chloroform mixed solvent, oxidize it at room temperature by bubbling in dry air for 2 hours, controlling approximately 30% of the thiol groups to form intermolecular disulfide bonds. Quench with ascorbic acid, cast into a film, and vacuum dry to obtain a slightly cross-linked star-shaped network PLA-PCL block copolymer.

[0044] Example 2

[0045] This embodiment describes a method for preparing a biodegradable esophageal stent, comprising the following steps:

[0046] S1. Polylactic acid, polycaprolactone, polyethylene glycol, carbon nanofibers, the star-shaped network PLA-PCL block copolymer prepared in Example 1, and talc are mixed in proportion, melt-blended and granulated, and then blended monofilaments are obtained using a high-pressure capillary rheometer; the diameter of the blended monofilaments is 0.2 mm, and the esophageal stent has a rhomboid mesh structure, with the monofilament weaving angle α satisfying: tanα°=2;

[0047] In this embodiment, the mass of polylactic acid (PLA) is 50g, the mass of polycaprolactone (PCL) is 50g, the molecular weight of polyethylene glycol (PEG) is 1000, and the added mass of PEG is 1% of the total mass of PLA and PCL, i.e., 1g; the added mass of carbon nanofibers is 1% of the total mass of PLA and PCL, i.e., 1g; the added mass of talc is 0.1% of the total mass of PLA and PCL, i.e., 0.1g; and the added mass of star-shaped network PLA-PCL block copolymer is 0.2% of the total mass of PLA and PCL, i.e., 0.2g.

[0048] S2. The blended monofilaments obtained in step S1 are woven into a mesh-like support skeleton on a mold by interlacing and pressing, and then heat-set at 160℃. After cooling, the skeleton is demolded.

[0049] S3. The thermoplastic polyurethane casting liquid loaded with bioactive substances is cast into a film and coated on the inner wall of the scaffold skeleton obtained in step S2. The film is heated at 160°C. In this embodiment, the heating is carried out by hot pressing to fuse the thermoplastic polyurethane film with the scaffold skeleton. After cooling, the esophageal stent is formed. The bioactive substance in this embodiment is silver nanoparticles.

[0050] Example 3

[0051] This embodiment describes a second method for preparing a biodegradable esophageal stent, comprising the following steps:

[0052] S1. Polylactic acid, polycaprolactone, polyethylene glycol, carbon nanofibers, the star-shaped network PLA-PCL block copolymer prepared in Example 1, and talc are mixed in proportion, melt-blended and granulated, and then blended monofilaments are obtained using a high-pressure capillary rheometer; the diameter of the blended monofilaments is 0.30 mm, and the esophageal stent has a rhomboid mesh structure, with the monofilament weaving angle α satisfying: tanα°=2;

[0053] In this embodiment, the mass of polylactic acid is 90g, and the mass of polycaprolactone is 10g; the molecular weight of polyethylene glycol is 5000, and the added mass of polyethylene glycol is 2% of the total mass of polylactic acid and polycaprolactone, i.e., 2g; the added mass of carbon nanofiber is 2% of the total mass of polylactic acid and polycaprolactone, i.e., 2g; the added mass of talc is 0.2% of the total mass of polylactic acid and polycaprolactone, i.e., 0.2g; and the added mass of star-shaped network PLA-PCL block copolymer is 0.3% of the total mass of polylactic acid and polycaprolactone, i.e., 0.3g.

[0054] S2. The blended monofilaments obtained in step S1 are woven into a mesh-like support skeleton on a mold by interlacing and pressing, and then heat-set at 170°C, and demolded after cooling.

[0055] S3. The thermoplastic polyurethane casting liquid loaded with bioactive substances is cast into a film and coated on the inner wall of the scaffold skeleton obtained in step S2. The film is heated at 170°C. In this embodiment, the heating is carried out by hot air to fuse the thermoplastic polyurethane film with the scaffold skeleton. After cooling, the esophageal stent is formed. The bioactive substances in this embodiment are silver nanoparticles and rapamycin in a mass ratio of 1:1.

[0056] Example 4

[0057] This embodiment describes a third method for preparing a biodegradable esophageal stent, comprising the following steps:

[0058] S1. Polylactic acid, polycaprolactone, polyethylene glycol, carbon nanofibers, the star-shaped network PLA-PCL block copolymer prepared in Example 1, and talc are mixed in proportion, melt-blended and granulated, and then blended monofilaments are obtained using a high-pressure capillary rheometer; the diameter of the blended monofilaments is 0.35 mm, and the esophageal stent has a rhomboid mesh structure, with the monofilament weaving angle α satisfying: tanα°=2;

[0059] In this embodiment, the mass of polylactic acid is 80g, and the mass of polycaprolactone is 20g; the molecular weight of polyethylene glycol is 20000, and the added mass of polyethylene glycol is 3% of the total mass of polylactic acid and polycaprolactone, i.e., 3g; the added mass of carbon nanofiber is 3% of the total mass of polylactic acid and polycaprolactone, i.e., 3g; the added mass of talc is 0.3% of the total mass of polylactic acid and polycaprolactone, i.e., 0.3g; and the added mass of star-shaped network PLA-PCL block copolymer is 0.4% of the total mass of polylactic acid and polycaprolactone, i.e., 0.4g.

[0060] S2. The blended monofilaments obtained in step S1 are woven into a mesh-like support skeleton on a mold by interlacing and pressing, and then heat-set at 180°C, and demolded after cooling.

[0061] S3. The thermoplastic polyurethane casting liquid loaded with bioactive substances is cast into a film and coated on the inner wall of the scaffold skeleton obtained in step S2. The film is heated at 180°C. In this embodiment, the heating is carried out by infrared irradiation to fuse the thermoplastic polyurethane film with the scaffold skeleton. After cooling, the esophageal stent is formed. The bioactive substance in this embodiment is rapamycin.

[0062] Example 5

[0063] Based on Example 3, this embodiment conducted the following experiments: PLA / PCL blended fibers with different diameter ratios were obtained at different stretching speeds; different DSC curves were obtained for PCL / PLA blended fibers with different ratios; DSC curves were obtained after annealing PCL / PLA blended fibers with different ratios at 160℃; different tensile strengths were obtained for PCL / PLA blended fibers with different ratios; different elongation at break of PLA / PCL blended fibers were obtained at different stretching speeds; and the modulus of blended fibers with different PLA / PCL ratios was obtained. The results are as follows: Figure 1 As shown, the following conclusions can be drawn:

[0064] Figure 1 a (Relationship between diameter and PCL content): As the PCL content increases (from 0% to 20%), the diameter of the monofilament exhibits different trends. At a stretching rate of 50 mm / s, the monofilament diameter gradually increases with increasing PCL content, from approximately 0.48 mm to approximately 0.52 mm. At a stretching rate of 200 mm / s, the monofilament diameter decreases slightly with increasing PCL content, from approximately 0.35 mm to approximately 0.33 mm. At a stretching rate of 350 mm / s, the monofilament diameter remains at a low level with increasing PCL content, between approximately 0.24 mm and 0.25 mm. This indicates that the addition of PCL has a significant impact on the monofilament diameter, and this impact varies with the stretching rate.

[0065] Figure 1 b (DSC curve): The position and shape of the melt peak (Endo peak) of the PLA / PCL blend changed with increasing PCL content (from 20% to 50%). At low PCL content (20%), the melt peak was sharp, indicating high crystallinity. As the PCL content increased, the melt peak gradually broadened, indicating decreased crystallinity, possibly because the addition of PCL disrupted the crystalline structure of PLA. This shows that the addition of PCL has a significant impact on the crystallization behavior of PLA.

[0066] Figure 1 c (PLA / PCL DSC curve at 160℃): At 160℃, the position and shape of the melt peak change with increasing PCL content (from 20% to 50%). At low PCL content (20%), the melt peak is relatively sharp, indicating that there is still some crystallinity at 160℃. As the PCL content increases, the melt peak gradually broadens, indicating that the crystallinity at 160℃ further decreases. This shows that at high temperatures, the addition of PCL still has a significant impact on the crystallization behavior of PLA.

[0067] Figure 1d (Relationship between tensile strength and PCL content): As the PCL content increases (from 0% to 50%), the tensile strength first increases and then decreases. The tensile strength reaches its maximum value of approximately 63 MPa when the PCL content is 10%.

[0068] As the PCL content continues to increase, the tensile strength gradually decreases, dropping to approximately 36 MPa at 50% PCL content. This indicates that an appropriate amount of PCL can improve the tensile strength of PLA / PCL blends, but excessive addition will reduce their strength.

[0069] Figure 1 e (Relationship between elongation at break and PCL content): As the PCL content increases (from 0% to 50%), the elongation at break shows a significant increasing trend. At a PCL content of 0%, the elongation at break is close to 0%. When the PCL content increases to 10%, the elongation at break rapidly increases to approximately 800%. With further increases in PCL content, the elongation at break continues to increase, reaching approximately 950% at 50%. This indicates that the addition of PCL significantly improves the ductility and toughness of the PLA / PCL blend.

[0070] Figure 1 f (Relationship between elastic modulus and PCL content): As the PCL content increases (from 0% to 50%), the elastic modulus gradually decreases. At 0% PCL content, the elastic modulus is approximately 1050 MPa. With increasing PCL content, the elastic modulus gradually decreases, dropping to approximately 550 MPa at 50%. This indicates that the addition of PCL reduces the stiffness of the PLA / PCL blend, making it more flexible.

[0071] In summary, the addition of PCL significantly affects the diameter, crystallization behavior, tensile strength, elongation at break, and elastic modulus of PLA / PCL blends. An appropriate amount of PCL (10%) can significantly improve tensile strength and elongation at break, but excessive addition will decrease tensile strength and elastic modulus. Furthermore, the addition of PCL disrupts the crystalline structure of PLA, reducing its crystallinity, especially at high temperatures.

[0072] Example 6

[0073] Based on Example 3, this embodiment conducted the following experiments: (a) DSC curves of different proportions of PEG-1000 additive; (b) DSC curves of different proportions of PEG-5000 additive; (c) DSC curves of different proportions of PEG-20000 additive; (d) Crystallinity of PLA / PCL blended fibers after adding different proportions of PEG additive; (e) Stress-strain curves of PLA / PCL blended fibers after adding different proportions of PEG additive; (f) Elastic modulus of PLA / PCL blended fibers after adding different proportions of PEG additive; (g) Yield strength of PLA / PCL blended fibers after adding different proportions of PEG additive; (h) Elongation at break of PLA / PCL blended fibers after adding different proportions of PEG additive.

[0074] The results are as follows Figure 2 As shown, the following conclusions can be drawn:

[0075] Figure 2 a, b, c: DSC curves (crystallization behavior analysis)

[0076] Figure 2 a(PLA / PEG) a -x% system, x=1~4%): The horizontal axis represents temperature (°C), and the vertical axis represents heat flow (Endo indicates exothermic / endothermic, here we look at the melting peak). With increasing PEG mass fraction (1%→4%), the intensity, width, and position of the melting peak change: the peak is sharper at low content (1%), and becomes wider and less intense at high content (4%). This indicates that the addition of PEG disrupts the crystallinity regularity of PLA, and the crystallinity of PLA decreases (or the crystallinity perfection decreases) with increasing PEG mass fraction.

[0077] Figure 2 b(PLA / PEG) o -x% system, x=1~4%): Similarly, as the PEG molar fraction increases (1%→4%), the melting peak broadens and the intensity decreases. This indicates that higher molar fractions of PEG have a more significant impact on PLA crystallization, and the crystallization behavior is more significantly affected by the number of PEG molecules (rather than mass).

[0078] Figure 2 c(PLA / PEG) o -x%, different PEG molecular weights): Comparison of PEG 1000 PEG 5000 PEG 20000 (1% content), differences in the position and shape of the melting peak: the smaller the molecular weight of PEG (e.g., PEG... 1000 The sharper the peak, the larger the molecular weight (e.g., PEG). 20000The wider the peak, the less interference PEG has with PLA crystallization (PLA crystals are more easily preserved); the larger the molecular weight, the more severe the disruption of crystal regularity.

[0079] Figure 2 d: Relationship between crystallinity and PEG content and molecular weight: The horizontal axis represents PEG content (1%~6%), and the vertical axis represents crystallinity (%). The three curves correspond to PEG... 1000 (Purple), PEG 5000 (Blue), PEG 20000 (Green): As the PEG content increases, the overall crystallinity shows an upward trend (especially PEG). 1000 and PEG 5000 ), but PEG 20000 The crystallinity of PEG increases slowly. At the same content, the smaller the molecular weight of PEG, the higher the crystallinity (PEG...). 1000 PEG 5000 PEG 20000 This indicates that an appropriate amount of PEG (especially low molecular weight PEG) can promote PLA crystallization, and the smaller the molecular weight of PEG, the more obvious the crystallization-promoting effect.

[0080] Figure 2 e: Stress-strain curves (pure PLA fiber vs. PLA fiber with PEG)

[0081] The horizontal axis represents strain (%), and the vertical axis represents stress (MPa). The curves include "pure PLA fiber" and PLA fibers with three types of PEG (1000, 5000, and 20000): pure PLA fiber has a steep stress-strain curve (high modulus) and low fracture strain (high brittleness); after adding PEG, the curve slope decreases (decreased modulus) and the fracture strain increases (improved toughness). Among different PEG molecules, PEG... 20000 The curve shows the largest fracture strain (best toughness) for PEG. 1000 Secondly, PEG 5000 The lowest value indicates that the addition of PEG significantly reduces the modulus of PLA and improves its toughness; however, the larger the molecular weight of PEG, the greater the sacrifice in strength and modulus.

[0082] Figure 2 f: Relationship between elastic modulus and PEG content

[0083] The horizontal axis represents PEG content (wt%), and the vertical axis represents elastic modulus (MPa). The three curves correspond to PEG content. 1000 (Red), PEG 5000 (Green), PEG 20000 (Blue): As the PEG content increases, the overall elastic modulus decreases (the modulus of PLA is weakened by PEG). At the same content, the larger the molecular weight of PEG, the lower the modulus (PEG...20000 <PEG 5000 <PEG 1000 At low contents (1%~3%), the modulus decreases slowly; at high contents (4%~6%), the decrease is significant. This indicates that the addition of PEG reduces the rigidity (modulus) of PLA, and higher molecular weight PEG has a stronger plasticizing effect, resulting in the greatest modulus loss.

[0084] Figure 2 g: Relationship between tensile strength and PEG content

[0085] The horizontal axis represents PEG content (wt%), and the vertical axis represents tensile strength (MPa). The three curves correspond to PEG content. 1000 (Red), PEG 5000 (Green), PEG 20000 (Blue): Tensile strength gradually decreases with increasing PEG content (e.g., PEG...) 1000、 PEG 5000、 PEG 20000 The values ​​are all at their lowest at around 6%. At the same content, medium molecular weight PEG has the highest tensile strength. 5000 PEG 1000 PEG 20000 High molecular weight PEG has the most significant impact on strength. This indicates that an appropriate amount of PEG (medium molecular weight, specific content) can change the tensile strength of PLA (synergistic toughening and strengthening), but excessive addition will lead to a decrease in strength due to phase separation or crystallization damage.

[0086] Figure 2 h: Relationship between elongation at break and PEG content

[0087] The horizontal axis represents PEG content (wt%), and the vertical axis represents elongation at break (%). The three curves correspond to PEG content. 1000 (Red), PEG 5000 (Green), PEG 20000 (Blue): As PEG content increases, PEG 1000 and PEG 5000 The elongation at break initially decreases and then levels off, PEG 20000 The elongation at break showed a generally slow decreasing trend. At the same content, PEG... 5000 PEG has the highest overall elongation at break. 1000 Second (PEG) 20000 <PEG 1000 <PEG 5000 ).

[0088] This indicates that while the addition of PEG can improve toughness and the elongation at break (strain index) increases with increasing PEG content, excessive addition will affect the mechanical properties of PEG.

[0089] In summary, it can be seen that PEG, as a plasticizer / modifier of PLA, has a significant regulatory effect on the crystallization behavior and mechanical properties (modulus, strength, and toughness) of PLA by its content and molecular weight. PEG disrupts the regularity of PLA crystallization, and the crystallinity increases with the increase of PEG content (more significant for low molecular weight PEG), but the melting peak is broadened (the degree of crystallization perfection decreases).

[0090] Modulus decreases significantly with increasing PEG content and molecular weight (resulting in decreased rigidity); appropriate amounts of PEG (medium molecular weight, specific content) can improve strength, while excessive amounts decrease it; modulus increases with increasing PEG content. Figure 2 (The stress-strain area of ​​e increases), and the elongation at break (strain) increases with increasing content.

[0091] Low molecular weight PEG (such as PEG) 1000 ) has advantages in "toughening and capacity enhancement"; high molecular weight PEG (such as PEG) 20000 ) is more significant in "significantly reducing modulus and improving toughness", but suffers greater strength loss; medium molecular weight PEG (such as PEG) 5000 It can toughen the material while maintaining moderate strength without damaging the blend structure.

[0092] Example 7

[0093] Based on Example 3, this embodiment conducts the following tests to evaluate the performance of esophageal stents with different structures: (a) modulus of different types of esophageal stents; (b) resilience of different types of esophageal stents; (c) radial support force of different types of esophageal stents; (d) strain-radial force curve of 90° covered esophageal stent; (e) 500-cycle compression test of rhomboid mesh structure esophageal stent; (f) images of esophageal stents with different structures.

[0094] The results are as follows Figure 2 As shown, the following conclusions can be drawn:

[0095] Figure 3 a: The relationship between modulus and weaving angle

[0096] The horizontal axis represents the weaving angle (30°, 60°, 90°, 120°), and the vertical axis represents the modulus (MPa). The three curves correspond to three mesh structures: Densegrids (purple): The modulus exhibits a "decreasing-increasing-decreasing" trend with angle, approximately 50 MPa at 60° and approximately 37 MPa at 120°. Sparsemesh (orange): The modulus exhibits an "increasing-decreasing-increasing" trend with angle, approximately 42 MPa at 60° and approximately 45 MPa at 120°. Diamondgrid (green): The modulus exhibits an "increasing-decreasing-stable" trend with angle, approximately 62 MPa (peak value) at 60° and approximately 48 MPa at 120°.

[0097] This indicates that the rhomboid mesh has the highest modulus at 60°, suggesting that the support has the best stiffness (resistance to deformation) at this structure and angle; the modulus of different meshes is more sensitive to angle.

[0098] Figure 3 b: Relationship between elastic rebound rate and weaving angle

[0099] The horizontal axis represents the weaving angle (°), and the vertical axis represents the elastic rebound rate (%, i.e., the percentage of the product that returns to its original shape after unloading). The three curves correspond to three different grid structures: Densegrids (purple): The rebound rate drops sharply at 60° (approximately 50%), rises to 88% at 90°, and remains at 88% at 120°. Sparsemesh (orange): The rebound rate continuously increases with the angle, reaching approximately 85% at 120°. Diamondgrid (green): The rebound rate continuously increases with the angle, reaching approximately 95% (highest) at 120°.

[0100] The results show that the rhomboid mesh has the best overall elastic rebound rate, especially at 120°, which is close to 95%, indicating that the structure has the strongest ability to recover its original shape after cyclic deformation; the dense mesh has an abnormally low rebound rate at 60°.

[0101] Figure 3 c: Relationship between radial support force and weaving angle

[0102] The horizontal axis represents the weaving angle (°), and the vertical axis represents the radial support force (N, i.e., the force with which the stent opens the esophagus). The three curves correspond to three grid structures: Densegrids (purple): The support force exhibits a "rise-fall-rise" trend with increasing angle, approximately 23N at 60° and approximately 25N at 120°. Sparsemesh (orange): The support force exhibits a "steady-rise" trend with increasing angle, approximately 22N (lowest) at 120°. Diamondgrid (green): The support force continuously increases with increasing angle, approximately 28N (highest) at 120°.

[0103] The results show that the rhomboid grid provides the best radial support, reaching 28N at 120°, which meets the clinical requirement of esophageal stents to "open and maintain their shape"; the sparse grid provides the weakest support.

[0104] Figure 3 d: Force-strain curve under cyclic loading

[0105] The horizontal axis represents strain (%), and the vertical axis represents force (N). The red curve represents the force change during the loading process, and the pink areas are marked "17.4N" (initial force) and "37.4N" (peak force). When the strain increases from 0 to 20%, the force rises rapidly to 37.4N; when the strain increases from 20% to 50%, the force fluctuates but remains above 20N.

[0106] This indicates that during cyclic loading (or deformation), the force output of the support is stable and has a clear elastic phase (the force rises rapidly before 20% strain, then fluctuates but still maintains support force), indicating that the structure has good fatigue resistance.

[0107] Figure 3 e: Stress-strain curve under cyclic loading

[0108] The horizontal axis represents tensile strain (%), and the vertical axis represents tensile stress (MPa). The five curves correspond to the number of cycles (0, 125, 250, 375, 500): as the number of cycles increases, the "slope (modulus)" and "peak stress" of the curves do not decrease significantly, and may even increase slightly.

[0109] This indicates that the mechanical properties (modulus and strength) of the stent did not significantly decrease after 500 cycles of loading, proving that the structure has strong durability and is suitable for long-term implantation.

[0110] Figure 3 f: Actual / microscopic image of the scaffold

[0111] The left side shows the black and white grid structure, and the right side shows the scaffold after transparent lamination. The grid structure is clear and densely woven; the lamination is tightly bonded to the grid without obvious delamination. This indicates that the scaffold's grid structure is well-formed and the lamination process is effective (the film and fiber mesh are tightly bonded), ensuring the integrity and stability of the scaffold.

[0112] In summary, Figure 3 Through performance comparisons of different mesh structures and weaving angles, as well as cyclic loading tests, it was concluded that the diamond grid exhibits the best performance in terms of modulus, elastic resilience, and radial support force, especially at a weaving angle of 120°, where its overall mechanical properties are optimal. After 500 cycles of loading, the stent showed no significant decrease in mechanical strength, demonstrating strong fatigue resistance and suitability for long-term clinical applications. The mesh structure was well-formed, and the composite was tight after lamination, ensuring the integrity and functionality of the stent.

[0113] As can be seen from the above embodiments: 1. In the esophageal stent of the present invention, both PLA and PCL are biodegradable materials. After fulfilling its supporting function, the stent can be gradually degraded and absorbed in the body, avoiding the need for secondary surgery for removal. The TPU film is harmless to the human body and can be directly excreted without causing harm. 2. The blending of PLA / PCL and additives achieves a balance between rigidity and toughness, with an elongation at break of over 1000% and a yield strength of 35 MPa. The TPU coating increases the elasticity and toughness of the material, and the fiber composite film material enhances the film strength, with a maximum tensile force of over 58 N. The woven structure gives the stent good radial support and axial flexibility, effectively reducing the risk of displacement. 3. The mesh structure allows epithelial cells to climb over, which is conducive to tissue healing. The coating is only on the inner side and does not affect the fixation of the stent to the outer side of the esophageal wall.

[0114] This invention relates to an esophageal stent based on a self-expanding biological esophageal stent to address benign esophageal diseases such as post-ESD stenosis and anastomotic stenosis. Compared to traditional metal stents and single-material biodegradable stents, this stent reduces the risk of displacement. The TPU internal membrane combines barrier function with drug carrier potential, and is expected to reduce the incidence and severity of post-ESD esophageal stenosis. It is a typical application of the integration of medicine and engineering. The biodegradable fiber stent developed in this invention can be migrated to other luminal organs in the future, such as biliary stents, urethral stents, and airway stents, leading to the development of a series of biodegradable interventional medical devices with huge market potential.

[0115] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention. Technical aspects, shapes, and structures not described in detail in this invention are all well-known technologies.

Claims

1. A biodegradable esophageal stent, characterized by, The esophageal stent is made of blended monofilaments. The raw materials of the blended monofilaments include polylactic acid, polycaprolactone, and additives, including polyethylene glycol, carbon nanofibers, star-shaped PLA-PCL block copolymers, and talc.

2. The biodegradable esophageal stent according to claim 1, wherein, The esophageal stent is provided with a functional inner lining, which is a thermoplastic polyurethane film loaded with bioactive substances. The thermoplastic polyurethane film is attached to the inner wall surface of the esophageal stent by heating and bonding to form a fiber-film composite structure.

3. The biodegradable esophageal stent of claim 2, wherein, The bioactive substance is selected from at least one of antibacterial agents or antiproliferative drugs; preferably, the antibacterial agent is silver nanoparticles and the antiproliferative drug is rapamycin.

4. The biodegradable esophageal stent of claim 1, wherein, The mass ratio of polylactic acid to polycaprolactone is (1~9):

1.

5. The biodegradable esophageal stent of claim 1, wherein, The polyethylene glycol has a molecular weight of 1,000-20,000, preferably 5,000; the added mass of the polyethylene glycol is 1%-3% of the total mass of polylactic acid and polycaprolactone.

6. The biodegradable esophageal stent of claim 1, wherein, The carbon nanofibers added are 1%-3% of the total mass of polylactic acid and polycaprolactone, and the talc added is 0.1%-0.3% of the total mass of polylactic acid and polycaprolactone.

7. The biodegradable esophageal stent of claim 2, wherein, The diameter of the blended monofilament is 0.2mm-0.35mm, and the esophageal stent has a rhomboid mesh structure with a monofilament weaving angle α satisfying: tanα°=2.

8. The biodegradable esophageal stent according to any one of claims 1-7, wherein, The star-shaped network PLA-PCL block copolymer is added at a mass of 0.2%-0.4% of the total mass of polylactic acid and polycaprolactone. The preparation method of the star-shaped network PLA-PCL block copolymer includes the following steps: In the absence of water and oxygen and in the presence of a catalyst, ε-caprolactone monomers are subjected to ring-opening polymerization using a multifunctional small molecule containing at least three hydroxyl groups as an initiator to obtain hydroxyl-terminated star-shaped polycaprolactone prepolymers. Without separating the star-shaped polycaprolactone prepolymer, lactide monomer was added to the reaction system, and the ring-opening polymerization reaction was continued to obtain a hydroxyl-terminated star-shaped PCL-b-PLA block copolymer. The terminal hydroxyl groups of the obtained star-shaped PCL-b-PLA block copolymer were reacted with a mercapto-containing compound to obtain a star-shaped PCL-b-PLA block copolymer with mercapto-terminated groups. The star-shaped PCL-b-PLA block copolymer with thiol end groups was oxidized under controlled conditions to form dynamic disulfide bonds between some of the thiol groups, resulting in a slightly cross-linked star-shaped network PLA-PCL block copolymer.

9. The biodegradable esophageal stent of claim 8, wherein, The controllable oxidation conditions are as follows: at room temperature, the star-shaped PCL-b-PLA block copolymer with thiol end groups is treated with a catalytic amount of oxidant, and the degree of oxidation is controlled so that 20% to 40% of the thiol groups are oxidized to form intermolecular disulfide bonds.

10. A biodegradable esophageal stent and a method for preparing the same, characterized by, The method for preparing the esophageal stent according to any one of claims 1-9 comprises the following steps: S1. Polylactic acid, polycaprolactone, polyethylene glycol, carbon nanofibers, star-shaped network PLA-PCL block copolymer and talc are mixed in proportion, melt-blended and granulated, and then blended monofilaments are obtained using a high-pressure capillary rheometer. S2. The blended monofilaments obtained in step S1 are woven into a mesh-like support skeleton on a mold by interlacing and pressing, and then heat-set at 160℃~180℃, and demolded after cooling. S3. Cast the thermoplastic polyurethane casting liquid loaded with bioactive substances into a film, or directly use a pre-made thermoplastic polyurethane film to cover the inner wall of the stent skeleton obtained in step S2, and heat it at 160℃~180℃ to fuse the thermoplastic polyurethane film with the stent skeleton. After cooling, the esophageal stent is formed.

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