Degradable absorbable suture, its preparation method and matching blood vessel suture device

Abstract

The disclosure belongs to the technical field of biomedical materials, and particularly relates to a degradable absorbable suture, a preparation method thereof and a matching blood vessel suture device. The degradable absorbable suture provided by the disclosure comprises a core layer, a drug-loaded sheath layer and a biological functional surface layer which are sequentially coated from inside to outside. The core layer comprises at least one wire, and is used for providing overall mechanical support force of the suture. The drug-loaded sheath layer is wrapped on the outer surface of the core layer, and is a drug-loaded matrix used for loading and controllably releasing functional drugs. The biological functional surface layer is wrapped on the outer surface of the drug-loaded sheath layer, and is provided with a plurality of through micro-holes used for defining drug release channels and regulating drug release rates. The in-vivo degradation period of the biological functional surface layer is greater than the in-vivo degradation period of the drug-loaded sheath layer, so as to match the time sequence repair process of the blood vessel tissue and realize long-acting and stable drug release.

Description

Technical Field

[0001] This disclosure belongs to the field of biomedical materials technology, and specifically relates to a biodegradable absorbable suture, its preparation method and matching vascular suture device. Background Technology

[0002] Vascular anastomosis is a core procedure in microsurgery, cardiovascular surgery, and transplantation. Clinically, biodegradable and absorbable sutures are commonly used to fix and connect severed vascular ends. Currently, commercially available biodegradable sutures only provide initial mechanical support during the suturing process, offering limited functionality. Once implanted, the suture acts as a foreign body, continuously stimulating local tissues and activating the body's coagulation pathways. Endothelial damage caused by surgical puncture at the anastomosis site means that newly generated endothelial cells cannot completely cover the wound in a short time, leaving exposed vascular matrix highly susceptible to platelet aggregation and thrombus deposition, leading to anastomotic occlusion and surgical failure. Simultaneously, vascular smooth muscle cells proliferate and migrate abnormally under the influence of injury signals, gradually causing excessive intimal hyperplasia at the anastomosis site, eventually leading to restenosis and significantly reducing the long-term patency rate of vascular anastomosis.

[0003] To avoid chronic inflammatory reactions caused by long-term foreign body retention, existing biodegradable sutures rely on the hydrolysis of polymers to achieve degradation and absorption. However, the degradation process of conventional homogeneous sutures is difficult to match with the vascular tissue repair cycle: premature degradation of sutures will result in loss of mechanical support and anastomotic tearing; excessively long degradation cycles will continuously induce inflammatory infiltration of foreign bodies, crowding out tissue regeneration space and hindering the remodeling and repair of vascular wall structure.

[0004] For the two major postoperative complications of thrombosis and intimal hyperplasia, systemic drug administration is often used in clinical practice. However, systemic administration has significant drawbacks: after drug dilution in the systemic circulation, the drug concentration at the local lesion of the vascular anastomosis is low, resulting in limited preventive and therapeutic effects; increasing the dosage will increase the metabolic burden on the liver and kidneys, increase systemic toxicity, and narrow the drug safety window. Currently, most publicly available drug-loaded sutures adopt a double-layer core-skin structure design, with the core bearing mechanical strength and the skin layer loading the drug for sustained release. Some studies have disclosed three-layer composite suture structures, but the outer layer of existing three-layer sutures is mostly set as a rapidly degradable layer, relying on the outer layer to dissolve and unblock the drug layer in advance to achieve drug release, lacking a physical barrier structure that can stably regulate the drug release flux; furthermore, existing layered sutures do not reverse-match the degradation cycle of each functional layer, and cannot rely on the temporal relationship of "slow degradation of the surface layer and medium degradation of the drug-loaded sheath layer" to couple the surface microporous structure to achieve long-term, stable, and targeted drug release, making it difficult to accurately adapt to the full-cycle repair needs of vascular anastomosis wounds from coagulation protection and inhibition of hyperplasia to endothelial integrity.

[0005] Therefore, the industry urgently needs a biodegradable suture that is suitable for vascular anastomosis scenarios, has graded degradation characteristics, and allows for precise controlled drug release through micropores, along with corresponding manufacturing processes and specialized vascular suturing instruments. Summary of the Invention

[0006] The purpose of this disclosure is to provide a biodegradable and absorbable suture and its preparation method, as well as a vascular suture device, which can precisely regulate the drug release rate while protecting the human body.

[0007] The objective of this disclosure is achieved through the following technical solution: In a first aspect, this disclosure provides a biodegradable absorbable suture, comprising a core layer, a drug-loaded sheath layer, and a biofunctional surface layer sequentially disposed from the inside out; the core layer includes at least one filament, which provides overall mechanical support for the suture; the drug-loaded sheath layer is wrapped around the outer surface of the core layer, and serves as a drug-loading matrix for loading and controllably releasing a functional drug; the biofunctional surface layer is wrapped around the outer surface of the drug-loaded sheath layer, and has a plurality of through-holes for defining drug release channels and regulating drug release rates; wherein the in vivo degradation period of the biofunctional surface layer is longer than that of the drug-loaded sheath layer, in order to match the temporal repair process of vascular tissue and achieve long-term stable drug release.

[0008] In some specific embodiments of this disclosure, the biofunctional surface layer maintains structural integrity in the early stages of vascular healing, continuously exerting a controlled-release effect as a physical barrier; the drug-loaded sheath layer preferentially degrades upon infiltration by body fluids, achieving dynamic attenuation of the drug release rate and adapting to the vascular endothelial regeneration cycle; the degradation cycle of the drug-loaded sheath layer matches the treatment cycle of vascular inflammation resolution and smooth muscle proliferation inhibition; and the degradation cycle of the biofunctional surface layer matches the repair cycle of complete vascular endothelial regeneration and vascular wall structural remodeling.

[0009] In some specific embodiments of this disclosure, the core layer is made of a biodegradable medical polymer material, and the tensile strength of the core layer meets the mechanical requirements of vascular anastomosis surgery; preferably, the material of the filament includes at least one of polydioxanone and polyhydroxyacetic acid.

[0010] In some specific embodiments of this disclosure, the drug-loaded sheath is a porous biodegradable polymer matrix, which includes a polylactic acid-glycolic acid copolymer. The copolymer has lactic acid structural units and glycolic acid structural units. By changing the molar ratio of the lactic acid structural units to the glycolic acid structural units, the degradation cycle of the drug-loaded sheath can be adjusted.

[0011] In some specific embodiments of this disclosure, the functional drug includes at least one of antithrombotic drugs and antiproliferative drugs.

[0012] In some specific embodiments of this disclosure, the micropores in the biofunctional surface layer are uniformly distributed on the surface of the biofunctional surface layer, and the micropores are the only external release channels for the drug; preferably, the pore diameter of the micropores in the biofunctional surface layer is larger than the pore diameter of the micropores in the drug-loaded sheath layer.

[0013] In some specific embodiments of this disclosure, the material of the biofunctional surface layer is a composite system formed by polycaprolactone and gelatin; the anticoagulant drug is loaded into the composite system of polycaprolactone and gelatin through physical blending; the gelatin can regulate the release rate of the anticoagulant drug.

[0014] In some specific embodiments of this disclosure, the surface of the biofunctional surface is covalently grafted with polypeptides, which can bind to integrin receptors on the cell surface with high specificity, thereby significantly enhancing the adhesion ability of endothelial cells, promoting cell spreading, and guiding cell directional migration.

[0015] In a second aspect, this disclosure provides a method for preparing a biodegradable absorbable suture, comprising the following steps: S1: A mechanically stable yarn is prepared by using the bulk material of the yarn through melt spinning process; S2: Mix the bulk material of the drug-loaded sheath with a pre-set functional drug and dissolve it in hexafluoroisopropanol to prepare a spinning solution; S3: Employs a coaxial spinning device, equipped with a specially designed coaxial needle structure to achieve the synchronous spinning process of two different fluids: the inner tube outputs biodegradable yarn and the outer tube outputs spinning solution; during the jet flight process, the spinning solution is solidified by solvent evaporation to form a core-sheath composite structure with an outer coating of drug-loaded sheath layer; S4: Formulate an emulsion containing anticoagulant drugs and biofunctional surface materials; S5: The emulsion is coated on the outer surface of the core-sheath composite structure and cured to form the biofunctional surface layer.

[0016] In some embodiments of this disclosure, step S4 includes: dissolving the anticoagulant drug and gelatin together in deionized water, while dissolving polycaprolactone in dichloromethane, and blending them to form a water-oil emulsion.

[0017] In some embodiments of this disclosure, step S5 includes: applying the emulsion to the outer surface of the drug-loaded sheath layer using an immersion-lifting method, and curing it to obtain a biofunctional surface layer.

[0018] In some embodiments of this disclosure, after step S5, the method further includes: S6: The gelatin component in the biofunctional surface layer is cross-linked using genipin cross-linking agent to adjust the gelatin to a preset target degree of cross-linking, thereby achieving controllable adjustment of the structure and performance of the biofunctional surface layer.

[0019] In some embodiments of this disclosure, after step S6, the method further includes: S7: Covalently grafting polypeptides onto the outer surface of the biofunctional surface layer composed of polycaprolactone and gelatin to impart specific biofunctionality to the suture surface layer.

[0020] In a third aspect of this disclosure, a vascular suture device is provided, adapted for use with the aforementioned biodegradable absorbable suture, the vascular suture device comprising a suture device body, a clamping assembly, and a threading assembly; The clamping assembly is used to fix the vascular anastomosis port, and the suture assembly is adapted to the diameter and hardness characteristics of the aforementioned biodegradable absorbable suture, in order to assist in completing the vascular anastomosis puncture and suturing operation.

[0021] The technical solution provided in this disclosure has the following technical contributions: (1) This disclosure provides a biodegradable absorbable suture, which consists of a core layer, a drug-loaded sheath layer, and a biofunctional outer layer from the inside out. The core layer is composed of multiple strands of silk, which provides stable tensile and tear-resistant mechanical anchoring force throughout the suturing process, ensuring the structural stability of the vascular anastomosis in the early stage of healing. The drug-loaded sheath layer serves as the main storage carrier for drugs and can load large quantities of antithrombotic and smooth muscle proliferation-inhibiting active drugs. The outer biofunctional outer layer wraps around the drug-loaded sheath layer to form a physical protective barrier, preventing the initial burst release of drugs under the flushing of body fluids. The three layers each perform mechanical bearing, drug storage, and drug release regulation functions. The structure is well-organized, with strong overall weaving / covering integration, smooth suturing and puncture, and less secondary damage to the vascular wall.

[0022] (2) This disclosure specifies that the degradation cycle of the biofunctional surface layer of the biodegradable absorbable suture is longer than that of the drug-loaded sheath. In the early stage of vascular healing, the slowly degrading biofunctional surface layer remains intact, continuously playing a drug flow-limiting barrier role; as the vascular endothelium gradually crawls to cover the wound, the drug-loaded sheath preferentially and gradually dissolves and degrades, the drug carrier is consumed simultaneously, and the drug delivery intensity naturally decreases; after the vascular wall completes structural remodeling, the surface layer slowly degrades and disappears, and the suture is completely absorbed by the body. This ensures sufficient mechanical strength of the suture during the critical healing period, while preventing it from remaining in the body as a foreign body for a long time, significantly reducing local aseptic inflammatory response, and reserving sufficient space for the regeneration of vascular extracellular matrix.

[0023] (3) The biofunctional surface layer of this disclosure is provided with interconnected micropores as fixed channels for drug diffusion. The drug release rate is physically limited by the micropore diameter and porosity. The difference in degradation rate between the two layers of materials forms a dynamic sustained-release system, which can steadily release the effective drug concentration according to the rhythm of vascular healing. The drug takes effect directly at the anastomotic lesion, with sufficient local drug concentration and low overall blood drug concentration. Under the premise of effectively preventing anastomotic thrombosis and inhibiting abnormal intimal hyperplasia, the systemic toxic side effects of systemic administration are greatly avoided, resulting in higher drug safety.

[0024] (4) This disclosure provides a method for preparing a composite suture with a structure that is compatible with the three-layer composite suture, as well as a matching vascular suture applicator. The preparation process can stably prepare composite sutures with uniform layers and controllable micropore parameters, and the batch stability of the products is high. The special suture applicator is adapted to the hardness and diameter characteristics of the suture, which reduces the difficulty of intraoperative suturing, shortens the duration of vascular anastomosis surgery, further reduces the probability of intraoperative vascular endothelial injury, and comprehensively improves the short-term patency rate and long-term prognosis of microvascular anastomosis surgery.

[0025] (5) This invention has a wide range of applications. It can adjust the ratio of polymer materials, micropore size and drug loading of each layer according to different diameter blood vessels and different surgical healing cycle requirements. It can be used for arteriovenous end-to-end anastomosis, free flap vascular anastomosis, and can also be adapted to cardiovascular bypass surgery and other scenarios. Attached Figure Description

[0026] Figure 1 This is a schematic diagram of the structure of a vascular suture device in the prior art; Figure 2 yes Figure 1 A top-view structural diagram; Figure 3 yes Figure 1 An enlarged structural schematic diagram of a local region M in the middle; Figure 4 for Figure 2 A schematic diagram of the cross-section of the conduit along its axial direction; Figure 5 This is a cross-sectional structural schematic diagram of one embodiment of the suture of this application; Figure 6 This is a schematic flowchart of the method for preparing the biodegradable and absorbable suture of this application. Detailed Implementation

[0027] The technical solutions of this disclosure will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of this disclosure, not all embodiments. Based on the embodiments of this disclosure, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this disclosure.

[0028] It should be noted that the terms "first" and "second" in this application are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of that feature. In the description of this application, "multiple" means at least two, such as two, three, etc., unless otherwise explicitly specified. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion. For example, a process, method, system, product, or apparatus that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products, or apparatuses.

[0029] Medical sutures are medical devices that physically connect tissues, close wounds, and assist in tissue repair. Medical sutures have a wide range of applications in modern medical surgery. However, current technology cannot reliably deliver medications, and sutures suffer from poor biocompatibility and inadequate biodegradability design.

[0030] See Figures 1 to 4 , Figure 1 This is a schematic diagram of the structure of a vascular suture device in the prior art. Figure 2 yes Figure 1 A top-view structural diagram. Figure 3 yes Figure 1 An enlarged structural diagram of a local region M in the middle. Figure 4 for Figure 2 A schematic cross-sectional view of the catheter along its axial direction. The vascular suture device includes a push rod 1, a drive handle 2, a lever 3, a suture blade 4, a suture tube 5, a return vessel 6, a suture 7, a foot wing 8, a catheter 9, a detachable needle tube 10, a detachable needle 11, a non-detachable needle 12, a suture channel 13, a sleeve 14, a connecting suture 15, and a hemostatic valve 16. The main function of the vascular suture device is to suture the puncture site of the blood vessel. The proximal part contains a pre-tied fisherman's knot, which can effectively avoid knot failure during surgery and save surgical time; the handle-like design at the handle helps to stabilize the entire device when removing the needle and withdrawing the instrument; the return vessel 6 provides a channel to ensure that the device enters the artery during use; the lever 3 is designed to facilitate opening and closing the suture feet. The catheter 9 consists of an inner tube 91 and an outer tube 92, and a hemostatic valve 16 is provided between the inner tube 91 and the outer tube 92. For the specific structure of the vascular suture device, please refer to the published application document (CN202411189680.6).

[0031] See Figure 5 , Figure 5This is a cross-sectional structural schematic diagram of one embodiment of the suture of this application. The first aspect of this application provides a biodegradable absorbable suture for vascular anastomosis. The suture includes a core layer 100, a drug-loaded sheath layer 200, and a biofunctional surface layer 300, sequentially arranged from the inside out. The core layer 100 includes at least one filament and provides overall mechanical support for the suture. The drug-loaded sheath layer 200 wraps around the outer surface of the core layer 100 and serves as a drug-loading matrix for loading and controllably releasing functional drugs. The biofunctional surface layer 300 wraps around the outer surface of the drug-loaded sheath layer 200 and has several through-holes. These micropores define drug release channels and regulate drug release rates. The in vivo degradation period of the biofunctional surface layer 300 is longer than that of the drug-loaded sheath layer 200 to match the temporal repair process of vascular tissue and achieve long-term, stable drug release.

[0032] In some specific embodiments of this disclosure, the core layer 100 is the innermost layer of the suture. It can be a single thread (also called a monofilament) or multiple threads arranged side by side or woven together. The core layer 100 has a certain strength, providing support for the outer material of the suture. At the same time, when the suture is sutured, the breaking strength of the core layer 100 meets the mechanical requirements of vascular anastomosis surgery, making it less prone to breakage and ensuring the quality of the suture. The material of the core layer 100 is a biodegradable medical polymer material that can be directly degraded after a period of time following suturing.

[0033] In some specific embodiments of this disclosure, the drug-loaded sheath 200 is a porous, biodegradable polymer matrix that can be directly degraded after a period of time following suturing. The drug-loaded sheath 200 is mainly used to load and release drugs, so that after suturing, the loaded drugs can be released through the drug-loaded sheath 200 to assist in drug therapy for vascular anastomosis. Since the suture is used to close the anastomosis, the drug release from the drug-loaded sheath 200 can be more precise and timely, avoiding direct systemic administration. At the same time, the drug release rate of the drug-loaded sheath 200 is matched with the degradation rate of the drug-loaded sheath 200 itself. By adjusting the degradation cycle of the drug-loaded sheath 200, the drug release cycle can be controlled, thereby controlling the drug therapy cycle.

[0034] In some specific embodiments of this disclosure, the biofunctional surface layer 300 is wrapped around the surface of the drug-loaded sheath layer 200. The biofunctional surface layer 300 is made of a biocompatible material with good affinity to human tissues, providing long-term protection. The biofunctional surface layer 300 forms a microporous barrier layer between the drug-loaded sheath layer 200 and the human tissue, preventing direct contact between the drug-loaded sheath layer 200 and the human tissue, thus affecting the drug release rate of the drug-loaded sheath layer 200. The drug released by the drug-loaded sheath layer 200 passes through the micropores in the biofunctional surface layer 300. It can be seen that the biofunctional surface layer 300 can more precisely control the drug release rate. Furthermore, the degradation cycle of the biofunctional surface layer 300 is longer than that of the drug-loaded sheath layer 200. In other words, even after the drug-loaded sheath layer 200 has completely degraded and released the drug, the biofunctional surface layer 300 still needs some time to degrade. The purpose of this design is that, generally speaking, the drug treatment cycle is shorter than the recovery cycle of human tissues. When the drug treatment is completed and the drug-loaded sheath layer 200 has completely degraded, the biofunctional surface layer 300 is still needed to protect human tissues for a period of time. At the same time, the micropores in the biofunctional surface layer 300 can help the human body excrete tissue fluid for the excretion of metabolic products.

[0035] In one embodiment, the core layer 100 includes a plurality of filaments, the filaments being made of at least one of poly(p-dioxanone) (PGA) and polyhydroxyacetic acid (PDO).

[0036] Specifically, a composite structure composed of multiple independent filaments is employed. This design allows the filaments to slide against each other under stress, effectively dispersing localized stress concentration and improving overall knot strength and structural toughness. Compared to a single thick filament, multiple thin filaments significantly increase the specific surface area, accelerating the material's degradation rate in vivo while maintaining the same dimensions as the core layer. Polyglycolic acid (PEG), as an excellent biodegradable material, is almost completely degraded after approximately four months of implantation. It exhibits high mechanical strength in the early stages of degradation, serving as a reliable temporary mechanical framework and providing necessary mechanical support during the critical stages of anastomotic healing. Poly(p-dioxanone) not only possesses sufficient tensile strength but is also softer than PEG, maintaining a high strength retention rate after knotting operations, improving surgical handling and reducing mechanical damage to fragile blood vessel walls. This material is completely absorbed by the body within approximately six months, and its degradation timeline closely matches the critical support period for vascular tissue healing (typically several months).

[0037] In one embodiment, the drug-loaded sheath 200 is a porous biodegradable polymer matrix, which includes polylactic acid-glycolic acid copolymer (PLGA). The copolymer has lactic acid structural units and glycolic acid structural units. By changing the molar ratio of lactic acid structural units to glycolic acid structural units, the degradation cycle of the drug-loaded sheath 200 can be adjusted.

[0038] Specifically, the porous fiber membrane has a microporous structure, which can be a porous fiber network structure constructed by electrospinning technology. This structure allows tissue fluid to permeate, which can promote drug release and metabolite excretion. The polylactic acid-glycolic acid copolymer is a copolymer obtained by polymerizing two monomers, lactic acid (LA) and glycolic acid (GA). By adjusting the ratio of the two monomers, lactic acid and glycolic acid, the degradation rate of the drug-loaded sheath 200 can be adjusted, thereby enabling the regulation of the drug release rate.

[0039] Porous fiber membranes possess unique microporous structures, typically fabricated using electrospinning techniques to create porous fiber networks with high specific surface areas and interconnected pores. This microporous structure not only exhibits excellent permeability, allowing tissue fluid to pass through freely, but also effectively promotes sustained drug release and timely removal of metabolic waste. Polylactic acid-glycolic acid copolymer (PLA-GA) is a biodegradable polymer material prepared by copolymerizing lactic acid (LA) and glycolic acid (GA) monomers. By adjusting the ratio of lactic acid and glycolic acid monomers, the degradation behavior of PLA-GA materials can be precisely controlled, thereby influencing the drug degradation rate. This characteristic allows PLA-GA to flexibly adjust the drug release rate, meeting the needs of different therapeutic scenarios.

[0040] Preferably, lactic acid (LA) and glycolic acid (GA) are used as the two monomers in the copolymer, with a ratio of 85:15. This optimized ratio effectively controls the degradation behavior of the material. Experimental and theoretical studies have shown that at this ratio, the complete degradation cycle of the material is approximately 3 to 6 months. This time window closely matches the critical cycle required for vascular anastomosis healing and drug therapy in common clinical vascular surgeries. Therefore, when used as a drug carrier or absorbable implantable device, this copolymer can provide stable mechanical support and drug release during the treatment period, and degrade and absorb in a timely manner after completing its repair function, avoiding the need for secondary surgical removal. It exhibits good biocompatibility and promising clinical application prospects.

[0041] Of course, in some other embodiments, the material of the drug-loaded sheath 200 can also be other materials with multiple monomers to regulate the degradation rate.

[0042] In one embodiment, the functional drug encapsulated in the drug-loaded sheath 200 includes at least one of an antithrombotic drug and an antiproliferative drug.

[0043] Specifically, antiproliferative drugs mainly include sirolimus and its analogues. These drugs effectively prevent abnormal proliferation of the vascular intima by inhibiting specific cell signaling pathways. In particular, antiproliferative drugs can significantly inhibit the excessive proliferation and migration of vascular smooth muscle cells, a mechanism of action that is particularly important for preventing stenosis at vascular anastomoses. Furthermore, by reducing excessive cell proliferation, these drugs can also reduce the risk of local thrombosis.

[0044] In one embodiment, the micropores in the biofunctional surface layer 300 are uniformly distributed on the surface of the biofunctional surface layer 300, and the micropores are the only external release channels for the drug; preferably, the pore size of the micropores in the biofunctional surface layer 300 is larger than the pore size of the micropores in the drug-loaded sheath layer 200.

[0045] Specifically, the micropore size of the biofunctional surface layer 300 is significantly larger than that designed in the drug-loaded sheath layer 200. This structural difference not only helps to increase drug loading but also optimizes the drug release kinetics model, resulting in smoother drug release. Specifically, the larger pore size of the biofunctional surface layer 300 provides more diffusion channels and attachment sites for drug molecules; while the smaller pore size of the drug-loaded sheath layer 200 helps to load more drug and more precisely control the drug release rate, ensuring continuous and stable drug release in the target region. This multi-layered pore size design makes the entire system exhibit better controllability and biocompatibility during drug delivery.

[0046] In one embodiment, the biofunctional surface layer 300 is a composite system formed by polycaprolactone (PCL) and gelatin; the anticoagulant drug is loaded into the composite system of PCL and gelatin through physical blending; the gelatin can regulate the release rate of the anticoagulant drug.

[0047] Specifically, the biofunctional surface layer 300 employs a material system prepared by blending polycaprolactone (PCL) and gelatin. PCL, as a biodegradable material, has a relatively long degradation cycle, typically requiring 1 to 2 years. It possesses excellent drug penetration properties and superior biocompatibility, providing stable and durable physical protection for the suture site. Furthermore, the long-term sustained release of drugs is achieved through the regulation of the material's degradation behavior. Gelatin, as a naturally derived biopolymer, not only exhibits good biocompatibility and degradability but also forms a gel in aqueous solution, making it easily degraded and absorbed by enzymes in the human body, and demonstrating high affinity for human tissues. By physically blending anticoagulants such as heparin into this composite system, the hydrophilic properties of gelatin and its rapid swelling in body fluids can be fully utilized. Combined with the microporous structure formed by PCL in the early stages of degradation, this promotes rapid drug release in the early postoperative period (within hours to days), thereby effectively preventing and treating acute thrombosis.

[0048] Of course, the material of the biofunctional surface layer 300 can also be other biodegradable and biocompatible materials.

[0049] In one embodiment, polypeptides are covalently grafted onto the surfaces of polycaprolactone and gelatin.

[0050] Specifically, polycaprolactone (PCL) and gelatin were introduced with specific polypeptide sequences via surface covalent grafting, primarily including RGD (arginylglycyl aspartate) polypeptide. Collagen, as an important natural biomaterial, has been widely proven to significantly promote the repair and regeneration of tissue defects, effectively supporting cell proliferation and tissue reconstruction. RGD polypeptide, as the most critical active recognition sequence in collagen molecules, can bind highly specifically to integrin receptors on the cell surface, thereby significantly enhancing endothelial cell adhesion, promoting cell spreading, and guiding directional cell migration. This series of biological responses helps to actively regulate the healing process of the vascular endothelium, accelerate the functional repair of damaged sites, and ultimately achieve more efficient and stable tissue regeneration results.

[0051] Combination Figure 5 and Figure 6 , Figure 6 This is a flowchart illustrating the method for preparing the biodegradable absorbable suture of this application. A second aspect of this application provides a method for preparing a biodegradable absorbable suture, the method comprising: S1: A yarn with stable mechanical properties is prepared by using the bulk material of the yarn through melt spinning process.

[0052] Specifically, at least one complete, continuous, unbranched filament is prepared through melt spinning. When preparing multiple filaments, they form a fibrous structure with a smooth surface and uniform diameter ranging from 0.1 mm to 0.04 mm. These filaments are not only structurally stable but also possess high strength, providing excellent support for the drug-loaded sheath layer 200 and the biofunctional surface layer 300. The filament material is at least one of poly(p-dioxanone) and polyglycolic acid.

[0053] S2: The bulk material of the drug-loaded sheath 200 is mixed with a preset functional drug and dissolved in hexafluoroisopropanol to prepare a spinning solution.

[0054] Specifically, the drug-loaded sheath 200 bulk material and the pre-set functional drug are dissolved together in hexafluoroisopropanol solvent. After thorough stirring and mixing, the mixture is completely and uniformly dispersed, ultimately forming a spinning solution with a certain viscosity and stability. The bulk material of the drug-loaded sheath 200 is a polylactic acid-glycolic acid copolymer.

[0055] S3: It adopts a coaxial spinning equipment and is equipped with a specially designed coaxial needle structure to realize the synchronous spinning process of two different fluids: the inner tube outputs biodegradable yarn and the outer tube outputs spinning solution; during the jet flight, the spinning solution is solidified by solvent evaporation to form a core-sheath composite structure with an outer coating of drug-loaded sheath layer.

[0056] Specifically, a coaxial electrospinning device is used, equipped with a specially designed coaxial needle structure, to achieve the synchronous spinning process of two different fluids: the inner tube delivers one fluid as the receiving core for the filament, while the outer tube delivers another spinning solution carrying the drug. By applying a high-voltage electrostatic field, the surface tension of the polymer solution or melt is overcome, causing it to be ejected from the needle, forming an extremely fine jet. During the jet's flight, the solvent gradually evaporates or the melt rapidly cools and solidifies, eventually depositing and accumulating on the receiving device to form a core-sheath composite structure with a nonwoven fabric-like structure. This process not only achieves efficient fiber preparation but also ensures that the final product has a uniform fiber distribution and excellent physical properties. This technology can directly and uniformly coat the surface of the core fiber (core layer 100) with a porous fiber sheath (drug-loaded sheath 200) composed of ultrafine fibers. This porous fiber sheath not only carries the drug, but also has a fine porous structure. This porous structure is conducive to the penetration and exchange of tissue fluid, which can promote the continuous release of drugs and the effective excretion of metabolites, and provide a more suitable microenvironment for the subsequent cell adhesion and growth.

[0057] S4: Formulate an emulsion containing at least 300 units of biofunctional surface material.

[0058] Specifically, at least the bulk material of the biofunctional surface layer 300 is dissolved in dichloromethane and thoroughly stirred or otherwise physically dispersed to form a stable and homogeneous emulsion.

[0059] In one embodiment, step S4 includes: S410: Anticoagulant material and gelatin are dissolved together in deionized water, while polycaprolactone is dissolved in dichloromethane, and then blended to form a water-oil emulsion.

[0060] Specifically, anticoagulant materials such as sodium heparin and gelatin are dissolved together in an appropriate amount of deionized water and stirred thoroughly to form a homogeneous aqueous solution. Simultaneously, polycaprolactone is dissolved in dichloromethane to prepare an oil phase solution. These two solutions are then blended to form a stable water-oil emulsion system. Because heparin is highly hydrophilic and difficult to mix directly and uniformly with oily polycaprolactone, heparin is encapsulated in aqueous droplets, thereby achieving uniform dispersion of heparin in the polycaprolactone oil phase.

[0061] S5: The emulsion is coated on the outer surface of the core-sheath composite structure and cured to form the biofunctional surface layer 300.

[0062] Specifically, an appropriate amount of emulsion is brought into full contact with the outer surface of the prepared drug-loaded sheath 200. By controlling the contact time and rate, the emulsion forms a continuous covering layer on the outer surface of the drug-loaded sheath 200, thereby obtaining a complete and functional bio-functional surface layer 300, and finally completing the preparation of the suture.

[0063] In one embodiment, step S5 includes: S510: The emulsion is coated onto the outer surface of the drug-loaded sheath layer 200 using the dip-coating method, and then cured to obtain the biofunctional surface layer 300.

[0064] Specifically, the heparin-containing polycaprolactone and gelatin blend emulsion is uniformly coated onto the outer surface of a pre-prepared and cooled drug-loaded sheath layer 200 using an impregnation-lift method, forming a composite coating with gradient release characteristics. When this composite coating comes into contact with postoperative body fluids, the outer polycaprolactone layer acts as a preliminary barrier due to its hydrophobic and slow-degrading properties, while the internal water droplets rapidly absorb water and dissolve, releasing the loaded heparin. This mechanism creates a highly efficient and rapid release channel for heparin, enabling it to quickly exert its anticoagulant function during the postoperative acute phase and effectively prevent thrombosis.

[0065] In one embodiment, after step S5, the method further includes: S6: The gelatin in the biofunctional surface layer 300 is cross-linked and treated by genipin cross-linking agent, and the gelatin is adjusted to the preset target degree of cross-linking, so as to achieve controllable adjustment of the structure and performance of the biofunctional surface layer 300.

[0066] Specifically, by using genipin as a crosslinking agent to crosslink gelatin materials, the desired degree of crosslinking can be effectively controlled. This is because gelatin itself dissolves too quickly in the body, failing to meet the stability requirements of certain applications. After crosslinking treatment, the mechanical properties of gelatin are significantly improved, and its resistance to degradation is also significantly enhanced, allowing the material surface to maintain structural integrity and functionality for a longer period in vivo. The degree of crosslinking can be precisely controlled by adjusting the reaction conditions: when the degree of crosslinking is low, the gelatin pore size is large, which is conducive to the rapid diffusion and release of heparin molecules; while when the degree of crosslinking is high, the gelatin pore size is small, thereby slowing down the release rate of heparin. Therefore, by precisely controlling the various parameters of the crosslinking reaction, the heparin release rate can be precisely managed to meet the needs of different clinical application scenarios.

[0067] In one embodiment, after step S6, the method further includes: S7: Covalently grafting polypeptides onto the outer surface of the biofunctional surface layer 300, which is composed of polycaprolactone and gelatin, endows the suture surface layer with specific biofunctionality.

[0068] Specifically, peptides are covalently grafted onto the outer surfaces of polycaprolactone and gelatin, specifically using chemical cross-linking agents such as carbodiimide to covalently link RGD-containing peptides to the already cross-linked gelatin and polycaprolactone materials. Compared to RGD peptides introduced solely through physical adsorption, which are prone to desorption and detachment in bodily fluids, covalently grafted RGD peptides exhibit higher stability and persistence. This stable interface modification continuously and stably provides cellular biological signals throughout the tissue healing process, effectively guiding cellular behavior. RGD peptides specifically promote the adhesion, spread, and migration of vascular endothelial cells. From a functional perspective, this modification is equivalent to reconstructing a molecular interface on the surface of the biofunctional surface layer 300. This interface not only covers the exposed suture base, preventing direct contact with human tissue, but also actively guides and accelerates the healing of the vascular endothelial wall, thereby accelerating the healing process. Furthermore, this strategy significantly inhibits late thrombosis and excessive intimal hyperplasia, effectively reducing the risk of restenosis and significantly improving the biocompatibility and overall functionality of the suture material.

[0069] A third aspect of this application provides a vascular suture device adapted for use with the aforementioned biodegradable absorbable suture. The vascular suture device includes a suture device body, a clamping assembly, and a threading assembly. The clamping assembly is used to fix the vascular anastomosis port, and the threading assembly is adapted to the diameter and hardness characteristics of the aforementioned biodegradable absorbable suture to assist in completing the vascular anastomosis puncture and suturing operation.

[0070] Specifically, a vascular suture device is a commonly used medical device in vascular surgery, primarily used for the repair and anastomosis of vascular injuries. Its application in cardiovascular interventional surgery is becoming increasingly widespread, achieving good clinical results. Vascular suture devices are mainly used for suturing puncture sites of the femoral artery and femoral vein, especially during large-diameter sheath interventional procedures. The suturing principle of the vascular suture device is similar to surgical vascular suturing. A guidewire is percutaneously inserted into the puncture site of the common femoral artery and common femoral vein during or after the procedure. Pulling the lever opens the foot wings of the vascular suture device, pressing the push rod causes two steel needles to penetrate the vessel wall and align with the sleeve inside the foot wings. After pulling the push rod to complete the suture threading, the vascular suture device is withdrawn. A suture trimmer is used to push the knot to the wound position, tighten the knot, and trim excess suture ends to complete the suturing. The suture will be permanently implanted in the body. With the application of this solution, the suture will degrade and be absorbed by the body within the expected timeframe, eliminating the need for secondary surgery and minimizing harm to the body. For details regarding the vascular suture system, please refer to the application document (CN202411189680.6).

[0071] The above specific embodiments are merely illustrative of the content of this disclosure and do not represent a limitation thereof. For those skilled in the art, various modifications and improvements can be made without departing from the spirit and substance of this disclosure, and these modifications and improvements are also considered to be within the scope of protection of this disclosure.

Claims

1. A biodegradable absorbable suture, characterized in that: It includes a core layer, a drug-loaded sheath layer, and a biological functional surface layer, which are arranged sequentially from the inside out; The core layer includes at least one thread, and the core layer is used to provide overall mechanical support for the suture. The drug-loaded sheath layer is wrapped around the outer surface of the core layer. The drug-loaded sheath layer is a drug loading matrix used to load and controllably release functional drugs. The biofunctional surface layer is wrapped around the outer surface of the drug-loaded sheath layer. The biofunctional surface layer is provided with a plurality of through micropores, which are used to define drug release channels and regulate drug release rate. The in vivo degradation cycle of the biofunctional surface layer is longer than that of the drug-loaded sheath layer, so as to match the time-series repair process of vascular tissue and achieve long-term stable drug release.

2. The biodegradable absorbable suture according to claim 1, characterized in that: The core layer is made of a biodegradable medical polymer material, and the tensile strength of the core layer meets the mechanical requirements of vascular anastomosis surgery; preferably, the material of the filament includes at least one of polydioxanone and polyhydroxyacetic acid.

3. The biodegradable absorbable suture according to claim 1, characterized in that: The drug-loaded sheath is a porous biodegradable polymer matrix, which includes a polylactic acid-glycolic acid copolymer. The copolymer has lactic acid structural units and glycolic acid structural units. By changing the molar ratio of the lactic acid structural units to the glycolic acid structural units, the degradation cycle of the drug-loaded sheath can be adjusted.

4. The biodegradable absorbable suture according to claim 1, characterized in that: The functional drugs include at least one of antithrombotic drugs and antiproliferative drugs.

5. The biodegradable absorbable suture according to claim 1, characterized in that: The micropores in the biofunctional surface layer are uniformly distributed on the surface of the biofunctional surface layer, and the micropores are the only external release channels for the drug; preferably, the pore diameter of the micropores in the biofunctional surface layer is larger than the pore diameter of the micropores in the drug-loaded sheath layer.

6. The biodegradable absorbable suture according to claim 1, characterized in that: The material of the biofunctional surface layer is a biodegradable biocompatible material, which is a composite system formed by polycaprolactone and gelatin; preferably, the anticoagulant drug is physically loaded into the composite system of polycaprolactone and gelatin; the gelatin can regulate the release rate of the anticoagulant drug.

7. The biodegradable absorbable suture according to claim 1, characterized in that: The surface of the biofunctional layer is covalently grafted with polypeptides, which can bind to integrin receptors on the cell surface with high specificity, thereby significantly enhancing the adhesion ability of endothelial cells, promoting cell spread, and guiding cell migration.

8. A method for preparing a biodegradable absorbable suture, characterized in that, The method for preparing the biodegradable absorbable suture according to any one of claims 1-7 comprises the following steps: S1: A mechanically stable yarn is prepared by using the bulk material of the yarn through melt spinning process; S2: Mix the bulk material of the drug-loaded sheath with a pre-set functional drug and dissolve it in hexafluoroisopropanol to prepare a spinning solution; S3: Employs a coaxial spinning device, equipped with a specially designed coaxial needle structure to achieve the synchronous spinning process of two different fluids: the inner tube outputs biodegradable yarn and the outer tube outputs spinning solution; during the jet flight process, the spinning solution is solidified by solvent evaporation to form a core-sheath composite structure with an outer coating of drug-loaded sheath layer; S4: Formulate an emulsion containing at least a biofunctional surface layer of bulk material; S5: The emulsion is coated on the outer surface of the core-sheath composite structure and cured to form the biofunctional surface layer.

9. The preparation method according to claim 8, characterized in that: Step S4 includes: Anticoagulant drugs and gelatin are dissolved together in deionized water, while polycaprolactone is dissolved in dichloromethane, and the mixture is blended to form a water-oil emulsion.

10. The preparation method according to claim 8, characterized in that: Step S5 includes: The emulsion was coated onto the outer surface of the drug-loaded sheath using an impregnation-lift method, and then cured to obtain a biofunctional surface layer.

11. The preparation method according to claim 8, characterized in that: Following step S5, the method further includes: S6: The gelatin component in the biofunctional surface layer is cross-linked using genipin cross-linking agent to adjust the gelatin to a preset target degree of cross-linking, thereby achieving controllable adjustment of the structure and performance of the biofunctional surface layer.

12. The preparation method according to claim 11, characterized in that: Following step S6, the method further includes: S7: Covalently grafting polypeptides onto the outer surface of the biofunctional surface layer composed of polycaprolactone and gelatin to impart specific biofunctionality to the suture surface layer.

13. A vascular suture device, characterized in that: The vascular suture device is adapted for use with the biodegradable absorbable suture as described in any one of claims 1-7, and includes a suture device body, a clamping assembly, and a threading assembly. The clamping assembly is used to fix the vascular anastomosis port, and the suture assembly is adapted to the diameter and hardness characteristics of the biodegradable absorbable suture as described in any one of claims 1-7, to assist in completing the vascular anastomosis puncture and suturing operation.

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