Anti-infective core-sheath drug-loaded biomimetic artificial ligament patch

Abstract

The present application relates to a kind of anti-infection skin-core drug-loaded biomimetic artificial ligament patch, adopt multi-layer space dense weaving framework;The multi-layer space dense weaving framework includes: a plurality of mutually parallel outer main warp, a plurality of mutually parallel inner drug-loaded warp;The outer main warp, inner drug-loaded warp are interwoven by weft system and form an integral whole;The inner drug-loaded warp adopts skin-core penetration controlled-release structure, the skin-core penetration controlled-release structure has drug-loaded matrix core layer and drug release skin layer, the drug release skin layer is covered by a plurality of high molecular fine filaments and is woven, and utilize the physical gap between filament as release channel.The present application realizes accurate release: abandon the traditional surface coating of extremely easy to fall off, through inner drug-loaded warp adopts skin-core penetration controlled-release structure, completely solve the " drug burst release " problem of drug-loaded patch in dynamic mechanical environment.

Description

Technical Field

[0001] This invention relates to a ligament patch, and more particularly to an anti-infective, drug-loaded, biomimetic artificial ligament patch, belonging to the field of medical supplies technology. Background Technology

[0002] Currently, in bone tumor resection (such as giant cell tumor of bone, osteosarcoma, etc.) and reconstruction of large-segment bone defects, artificial ligaments or meshes (tumor strips) are often used to reconstruct the biomechanical connections of joint capsules, tendons, or ligaments. Clinically, woven meshes similar to the French LARS (Ligament Advanced Reinforcement System) are widely used. These meshes are typically made of polyethylene terephthalate (PET) fibers, and their core mechanical structure employs a special spatial weaving method: straight warp threads are interwoven to lock the curved weft threads. This structure effectively resists lateral shear forces during joint movement, prevents mesh slippage and unraveling, and provides excellent biomechanical support.

[0003] However, this type of ligament woven mesh has the following drawbacks:

[0004] Lacking active anti-infection capabilities, patients are highly susceptible to biofilm formation: After bone tumor resection and prosthesis replacement, the surgical wound is large and often accompanied by the implantation of large pieces of bone cement and metal prostheses. Patients with low local immunity are at extremely high risk of deep infections. Existing pure PET woven materials such as LARS mesh are bioinert and lack any antibacterial function, making them highly susceptible to becoming a breeding ground for bacterial colonization, thus forming a biofilm that is difficult for the immune system or systemic antibiotics to clear.

[0005] Traditional drug-loaded coatings are highly susceptible to failure (burst release) under dynamic stress: In existing technologies, if a simple drug coating is applied to the surface of a mesh (such as Vijoo sutures), the coating is easily "physically scraped off" and detaches over a large area within a short period after surgery due to the friction and shearing action between the internal fibers caused by high-frequency flexion, extension, and rotation of the joint. This not only leads to a "burst release" of the drug in a very short time, causing local tissue toxicity, but also fails to effectively cover the high-risk period for infection 4-6 weeks after surgery. Summary of the Invention

[0006] This invention aims to address the technical shortcomings of existing pure PET mesh, such as the lack of anti-infection capabilities and the inability of conventional drug-loaded coatings to resist mechanical wear at joints. It provides a novel patch that achieves a balance between mechanical fatigue resistance and stable localized anti-infection for 4-6 weeks by precisely defining the parameters of the underlying textile yarn bundles and integrating drug-loaded warp threads into a specific weaving matrix using a "core-skin structure."

[0007] To solve this technical problem, the present invention adopts the following technical solution: an anti-infective core-loaded drug-inspired biomimetic artificial ligament patch, employing a multi-layered spatially dense woven structure; the multi-layered spatially dense woven structure includes: multiple parallel outer main warp threads 1 and multiple parallel inner drug-loaded warp threads 3; the outer main warp threads 1 and the inner drug-loaded warp threads 3 are interwoven into one piece by a weft system; the inner drug-loaded warp threads 3 adopt a core-loaded permeation controlled-release structure, the core-loaded permeation controlled-release structure having a drug-loaded matrix core layer and a drug sustained-release skin layer; the drug sustained-release skin layer is woven from multiple strands of polymer filaments, and utilizes the physical gaps between the filaments as drug release channels.

[0008] Preferably, the weft system is a wavy weft system, and the outer main warp 1 and the inner medicine-carrying warp 3 are formed by the vertical interweaving of the wavy weft. The multi-layered spatial dense weaving structure also includes at least one set of straight third warp 4 that are parallel to each other. The at least one set of straight third warp 4 is longitudinally inserted into the multi-layered spatial dense weaving structure and interwoven and locked with the wavy weft for reinforcement.

[0009] Preferably, the drug-loaded matrix core layer is made of polylactic acid-glycolic acid copolymer, and the drug sustained-release skin layer is made of medical-grade PET polymer layer; the polylactic acid-glycolic acid copolymer is a blend matrix of LA lactic acid:GA glycolic acid in a molar ratio of 50:50 and triclosan.

[0010] Preferably, the ratio of the cross-sectional area of ​​the drug-releasing outer layer to the drug-loaded matrix core layer is 4:1 to 1:2, preferably 1:1 or 1:2; structurally, the drug-releasing outer layer completely encapsulates the drug-loaded matrix core layer, isolating it from direct mechanical friction; mechanistically, the physical gaps naturally existing during the weaving of the outer multi-strand PET filaments are used as drug release channels to limit the rate of water penetration and drug dissolution, eliminating burst release, while the high-strength PET outer layer withstands external mechanical friction, preventing the internal drug core from being physically scraped off.

[0011] Furthermore, the wavy weft yarn adopts a knotted weft yarn 2 with elasticity and stretching. The outer main warp yarn 1 and the inner medicine-carrying warp yarn 3 each form a weaving node with the knotted weft yarn 2 at the wavy bend of the knotted weft yarn 2, forming a planar matrix alternating arrangement structure.

[0012] Furthermore, the planar matrix alternating arrangement structure: on the unfolded plane, the outer main warp 1 and the inner drug-carrying warp 3 are periodically arranged in parallel alternation at a ratio of 1:1, 2:1, 3:1 or 4:1, and the outer diameters of both are consistent, both being 0.4-1.2mm; through this dense interweaving of high-strength pure PET fibers, the ultimate tensile load of the overall patch is structurally shared.

[0013] Preferably, the weft system uses independent oblique weft 6 without elasticity. The independent oblique weft 6 forms a weaving node with the inner drug-carrying warp 3 on the inner side and is fixedly connected to the selected outer main warp 1 on the outer side. At least one of the selected outer main warp 1 is not connected to the independent oblique weft 6. Adjacent outer main warp 1 are also connected by a wavy outer knotted weft 5 to form a weaving structure. The whole structure forms a three-dimensional spatial decoupled weaving structure.

[0014] Furthermore, in the spatial topology of the ligament patch thickness direction, the three-dimensional spatial decoupled weft structure introduces independent inelastic PET weft yarns as independent oblique weft yarns 6. These independent oblique weft yarns 6 do not participate in the outer wavy knots, but instead interweave in a Z-shape along the Z-axis, specifically used to physically connect and anchor the inner drug-loaded warp yarns to the nodes of the outer main skeleton. Through the independent oblique weft yarns 6, the relative slippage of the inner and outer fibers during severe deformation is restricted, thus avoiding direct friction between the drug-loaded fibers and the outer skeleton from a physical structural perspective.

[0015] Preferably, the aperture of the three-dimensional mesh of the multi-layered spatial dense woven structure is maintained between 100 and 300 μm to facilitate intraoperative bone cement anchoring and postoperative fibroblast ingrowth.

[0016] Furthermore, the outer main warp 1, serving as the load-bearing skeleton, adopts a multi-strand multifilament twisted structure, consisting of 3-5 strands of PET multifilament twisted together, with each strand having a denier of 200D-400D. The total diameter of the outer main warp 1 is controlled between 0.4-1.2mm. The wavy weft yarn adopts a fine multifilament structure, consisting of 1-2 strands of PET multifilament, with a denier of 100D-150D and a total diameter controlled between 0.2-1.0mm. To avoid the fine yarn causing a "cutting effect" on the outer main warp 1, the ratio of the diameter of the wavy weft yarn to that of the outer main warp 1 is 1:2 to 1:1, in order to increase the contact area and disperse the lateral shear force during high-frequency joint movements. The straight third warp 4 achieves the straight insertion and locking of the wavy weft yarn knots, also adopting a PET multifilament structure, with each strand of 100D-200D multifilament twisted together, and a diameter controlled between 0.2-0.6mm.

[0017] Furthermore, to achieve spatial connection between the inner and outer layers, the independent oblique weft 6 is made of inelastic medical-grade PET fiber with a multifilament structure and a wire diameter controlled at 0.1-0.2mm. The independent oblique weft 6 is obliquely interwoven in a Z-shape or cross shape in three-dimensional space, and is specifically used to physically connect the inner drug-carrying warp 3 with the outer main warp 1.

[0018] The beneficial effects of this invention are as follows:

[0019] 1) Achieve precise sustained release: Abandoning the traditional surface coating that is extremely easy to fall off, the inner drug-carrying meridian adopts a core-skin permeation controlled release structure, which completely solves the problem of "drug burst release" of drug-carrying patches under dynamic mechanical environment.

[0020] 2) Revolutionary local anti-infection ability: As PLGA degrades, triclosan can form a long-lasting antibacterial zone around the patch during the high-risk period after bone tumor resection, fundamentally reducing the rate of deep infection.

[0021] 3) As an optional solution, precise matching of the bottom layer yarn parameters: the number of strands and diameter parameters of the main warp (coarse multifilament, high tensile strength), weft (fine multifilament, dense knot), and third warp (flexible multifilament, interlaced locking). This bottom layer textile engineering design, with its combination of coarse and fine yarns and all-multifilament structure, maximizes the optimization of the patch's shear resistance and dynamic fatigue life.

[0022] 4) As an optional solution, an independent oblique latitude line is introduced: the drug-loaded layer and the stress-bearing skeleton are perfectly spatially isolated and mechanically decoupled, ensuring that triclosan is released stably in strict accordance with a 4-6 week cycle. Attached Figure Description

[0023] Figure 1 This is a schematic diagram of the co-weft integral braided structure of the anti-infection core-loaded drug-inspired biomimetic artificial ligament patch from a "side-standing" perspective in the first embodiment of the present invention. Mechanical basis: The inner and outer layers share the same knotted weft yarns (1:1 ratio), forming a unified whole resistant to shear stress.

[0024] Figure 2 This is a schematic diagram of the overall co-weft braided structure of the anti-infection core-loaded drug-inspired biomimetic artificial ligament patch from a "top-down" perspective, as shown in the first embodiment of the present invention. It illustrates the locking structure of the straight third warp. Mechanical mechanism: The third warp intersects vertically, firmly locking the knotted weft threads and preventing lateral slippage.

[0025] Figure 3 This is a schematic cross-sectional view of the inner drug-loaded warp. It shows the core-sheath structure and covering yarn process of the inner drug-loaded warp.

[0026] Figure 4 This is a three-dimensional perspective overview of the anti-infection core-loaded drug-inspired biomimetic artificial ligament patch in the first embodiment of the present invention. It shows the highly dense biomimetic ligament spatial weave structure.

[0027] Figure 5 This is a schematic diagram of the independent oblique latitude suspension anchorage of the anti-infection core-loaded drug-inspired biomimetic artificial ligament patch from a "side-standing" perspective, as shown in the second embodiment of the present invention. It illustrates the independent oblique latitude suspension anchorage structure.

[0028] In the diagram, 1. Outer main meridian, 2. (Shared) knotted weft, 3. Inner medicine-carrying meridian, 4. Straight third meridian, 5. Outer knotted weft, 6. Independent oblique weft. Detailed Implementation

[0029] The present invention will be further described below with reference to the accompanying drawings and specific embodiments.

[0030] This invention provides an anti-infective core-loaded drug-inspired bionic artificial ligament patch (hereinafter referred to as "patch"), which adopts a multi-layered, densely woven structure. Through precise definition of the specifications of the bottom yarn bundle and multiple protective structures for the drug-loaded warp, it achieves a balance between mechanics and long-lasting sustained release.

[0031] Example 1:

[0032] See Figure 1 , Figure 1 The display shows the co-weave integral weave structure of the patch from a "side-standing" perspective.

[0033] See Figure 2 , Figure 2 The display shows a portion of the patch from a top-down view of the overall weft knitting structure.

[0034] See Figure 4 , Figure 4 The image shown is a 3D perspective view of the patch.

[0035] The three figures above are corresponding to each other and can be used together to understand the structure of the patch:

[0036] The multi-layered, densely woven structure includes: multiple parallel outer main warp threads 1, multiple parallel inner medicine-carrying warp threads 3, and at least one set of parallel straight third warp threads 4; the outer main warp threads 1 and the inner medicine-carrying warp threads 3 are connected by wavy weft threads vertically to form a whole; the at least one set of straight third warp threads 4 are inserted between the inner and outer sides and are fixedly connected to the wavy weft threads for reinforcement;

[0037] It should be emphasized that the inner drug-carrying warp 3 adopts a core-skin permeation controlled-release structure, which has a drug-carrying matrix core layer and a drug sustained-release skin layer.

[0038] The mechanical support layer of this patch is made of medical-grade polyethylene terephthalate (PET) fibers of different specifications, twisted and woven with a specific number of strands. The specific parameters are as follows:

[0039] Outer main warp 1 (load-bearing skeleton): adopts a multi-strand twisted structure. Preferably, it is made of 3-5 strands of PET multifilament twisted together, with each multifilament having a specification of 200D-400D (denier), and the main warp diameter controlled at 0.4-1.2mm (preferably 0.5mm or 1.0mm). The multi-strand twisting ensures extremely high tensile strength and fatigue resistance in the longitudinal direction of the patch.

[0040] Knotted Weft 2 (Interlaced Knotting Layer): Employs a finer multifilament structure to ensure both dense weaving and flexible knotting. Preferably composed of 1-2 strands of PET multifilament, with a specification of 100D-150D and a main diameter controlled between 0.2-1.0mm. To avoid a "cutting effect" (stress concentration) on the main warp yarns from the finer yarns, the ratio of weft yarn diameter to main warp yarn diameter is preferably 1:2 to 1:1 (e.g., when the main warp yarn is 1.0mm, the weft yarn is preferably 0.5-1.0mm) to increase the contact area and disperse the lateral shear force during high-frequency joint movements.

[0041] Straight Warp 4 (Flexible Locking Thread): To achieve absolutely straight insertion and locking of the weft knots, this warp abandons easily broken monofilaments and also adopts a PET multifilament structure. The preferred specification is 1-3 strands of multifilament twisted (100D-200D), with a wire diameter controlled at 0.2-0.6 mm (preferably 0.5 mm). The multifilament structure can not only pass straight through and firmly lock the knots of the weft threads (preventing longitudinal filament pulling), but also maintain the flexibility matching the overall mesh, providing sufficient longitudinal tensile fatigue life.

[0042] See Figure 3 The inner drug-carrying warp 3 employs a dual structure of microscopic controlled release and macroscopic weaving. This invention abandons the traditional surface coating process, achieving a unity of mechanics and sustained release through the "core-skin cross-section" at the microscopic level and the "three-dimensional spatial decoupled weaving" at the macroscopic level. Specific structural features are as follows:

[0043] Microscopic level: The "physical core-skin structure" of the drug-carrying warp (formed by the covering yarn process):

[0044] The inner core layer (core): a flexible polymer monofilament or multi-strand filament made by blending lactic acid-glycolic acid copolymer (PLGA), preferably with a LA (lactic acid):GA (glycolic acid) molar ratio of 50:50, with triclosan. The mass percentage (wt%) of triclosan in the blend matrix is ​​strictly limited to 1%-20%, preferably 5%-10%. It possesses excellent bending flexibility.

[0045] The outer skin (armor) and its molding process: Employs a mature tubular weaving or spiral winding process from traditional textile science. Specifically, 8 to 32 strands (preferably 12, 16, or 24 strands) of medical-grade PET filaments (such as single 10D-50D ultrafine multifilaments) are tightly wrapped around the PLGA core layer in a cross-mesh or spiral pattern using a conventional covering yarn machine or multi-spindle weaving machine, forming a tubular physical protective sheath.

[0046] Physical channel drug release mechanism: Directly utilizes the natural physical gaps between the multiple strands of PET filaments in the outer layer. Body fluids seep in through the gaps between the filaments and trigger the degradation of the PLGA core layer, allowing drug molecules to be released smoothly along the gaps; at the same time, the high-strength PET outer layer withstands external mechanical friction, preventing the internal drug core from being physically scraped away.

[0047] Cross-sectional ratio parameters: The ratio of the cross-sectional area (or volume) of the PET outer skin layer to the inner slow-release core layer is 4:1 to 1:2 (preferably 1:1 or 1:2).

[0048] Scientific Explanation of the PLGA (LA:GA=50:50) Ratio: Clinical Needs: After bone tumor resection and large-segment prosthesis replacement, the high-risk period for deep infection (SSI) is typically concentrated in the 4-6 weeks postoperatively. Therefore, we need to maintain a stable drug release above the minimum inhibitory concentration (MIC) during this period. Perfect Match between Ratio and Drug Release Kinetics: The degradation rate of polylactic-co-glycolic acid copolymer (PLGA) is highly dependent on the monomer ratio of LA to GA. Classic literature (Ramchandani, M., et al. Journal of Controlled Release 43 (1997): 161-173) confirms that when the LA:GA ratio is 50:50, the complete degradation period of the polymer in the body fluid environment is 6-8 weeks. Non-Obviousness of Parameters: In pharmacokinetic design, to ensure continued drug dissolution 4-6 weeks postoperatively, the degradation period of the polymer carrier matrix must be slightly longer than the target drug release period. The PLGA 50:50 ratio, with its 6-8 week bulk erosion period, provides a stable 4-6 week release window for triclosan, preventing premature drug release due to carrier disintegration. Increasing the LA ratio (e.g., 85:15, with a degradation period as long as 26 weeks) results in excessively low early release concentrations; increasing the GA ratio leads to excessively rapid degradation. Therefore, 50:50 is the optimal ratio for achieving the optimal anti-infective time window for patch therapy.

[0049] The selection of the core layer drug loading (1%-20%) parameter is based on the following: This invention precisely limits the mass percentage of triclosan in the PLGA core layer to 1%-20% (preferably 5%-10%), which is based on both biomechanical and pharmacokinetic considerations.

[0050] Lower limit requirement (≥1%): After surgery for bone tumors, the wound area is large. If the drug loading is less than 1%, during the slow degradation process of 4-6 weeks, the concentration of triclosan released locally will not be able to reach the minimum inhibitory concentration (MIC) against common orthopedic pathogens (such as Staphylococcus aureus and MRSA), resulting in the failure of anti-infection.

[0051] Upper limit requirement (≤20%): As a small molecule compound, if triclosan's doping ratio in the PLGA polymer matrix exceeds 20%, it will severely disrupt the intermolecular forces of the PLGA chain segments, causing the core fiber to lose its original "flexibility and toughness" and become extremely brittle. At the same time, excessive drug aggregation will destroy the polymer's density, allowing body fluids to penetrate instantly, triggering severe drug "burst release" and local toxicity. Therefore, 5% to 10% is the optimal balance point that balances "core layer flexibility without breakage" and "long-lasting and stable antibacterial effect".

[0052] A perfect balance between spatial drug loading capacity and low-toxicity sustained release (safety demonstration in large-segment reconstruction scenarios): Traditional surface coating processes are limited by surface area, resulting in extremely low drug loading capacity. If the coating thickness is forcibly increased, large-area detachment (burst release) is likely to occur under dynamic stress, instantly causing severe local tissue toxicity. This invention, however, employs a "solid core-skin structure." Taking a bus diameter of 1mm, a core-skin cross-section ratio of 1:1, and a core layer drug loading of 10% as an example, the absolute total triclosan content per centimeter of drug-loaded meridian can reach approximately 480μg (tens of times that of traditional coatings). Taking a clinically extreme case of 10cm femoral tumor resection and reconstruction (patch area approximately 100 square centimeters) as an example, if this embodiment (structural scheme one) (1:1 alternating meridians) is adopted, and the optimal parameters of 5% drug loading and a core-skin ratio of 1:2 are selected, the total triclosan drug loading of the entire patch is approximately 25-30mg. Under the dual controlled release of PLGA and PET skin, the release is forcibly extended to a stable dissolution period of 4-6 weeks, with a daily release of approximately 700 μg. Considering the daily turnover of 50-100 mL of tissue fluid in the large dead space after bone tumor surgery, and the protein binding rate of triclosan in protein-rich exudate exceeding 95%, its local "effective free concentration" is naturally limited to around 0.3-0.5 μg / mL. According to literature reports, the concentration threshold at which triclosan exhibits significant toxicity to human fibroblasts is typically above 1.0-3.0 μg / mL, while its minimum inhibitory concentration (MIC) against Staphylococcus aureus is only 0.01-0.1 μg / mL. The sustained-release mechanism of this invention, combined with the dynamic dilution effect of local body fluids, precisely falls within the safe therapeutic window of "above the pathogenic bacteria MIC and below the human cytotoxicity threshold." It completely solves the technical contradiction in traditional technology that "high drug loading inevitably leads to high local burst toxicity", and achieves a perfect balance between long-term anti-infection effect of large implants and tissue biosafety.

[0053] Macro level: The patch as a whole has a "three-dimensional decoupled braided structure" in which the above-mentioned "core-carrying drug-loaded warp" and "pure PET main warp" are three-dimensionally composite braided.

[0054] 1. Load-bearing frame (outer main warp): made of multiple strands of pure PET filaments twisted together, without drugs, providing high-strength tensile support.

[0055] 2. Macroscopic Coordination and Displacement Decoupling: The pure PET main warp and the drug-loaded warp are arranged in parallel and alternately in a specific ratio (e.g., 1:1, 2:1, 3:1, or 4:1) periodically, and their outer diameters can remain consistent (0.4-1.2mm). In Example 2, suspension anchoring is achieved through independent Z-axis weft lines, realizing the physical decoupling of the inner and outer layers under stress (Structural Scheme 2).

[0056] It should be noted that drug-loaded sustained-release technology is already used in current commercial medical devices. For example, Johnson & Johnson's Vicryl Plus antibacterial sutures (core patents such as US20040185250A1 and US8156718B2) use a copolymer of glycolide and lactide (Polyglactin 910) combined with triclosan. However, such existing technologies mostly employ a "surface coating process" or a "bare suture structure without a protective layer," which is only suitable for soft tissue suturing with low stress. Therefore, the inner drug-loaded warp suture 3 in this embodiment can be considered, macroscopically, as an existing "bare suture structure without a protective layer" with an added drug-loaded skin layer.

[0057] Therefore, the core layer of the inner drug-carrying warp 3 used in this invention is existing technology in principle.

[0058] Spatial arrangement and tissue engineering parameters:

[0059] The ratio of alternating main warp and inner warp: In the overall warp arrangement of the patch, the outer main warp (pure mechanical PET) and the inner drug-loaded warp (skin-core structure) are woven alternately in a ratio of 1:1, 2:1, 3:1, or 4:1. This ensures that the patch has a pure mechanical fiber content of over 75% to 80% and that the drug-loaded fibers are evenly distributed on the side of the wound adhering to the bone.

[0060] Optimal pore size limitation: The overall weaving density of the patch is precisely controlled, so that the pore size of the three-dimensional mesh is strictly maintained between 100 and 300 μm, which is conducive to bone cement anchoring during surgery and fibroblast ingrowth after surgery.

[0061] Inner and outer space connection and arrangement mechanism:

[0062] Corresponding to the co-weft integral knitting structure in this embodiment, Figure 1Connection Mechanism: The inner drug-loaded warp and the outer main warp share an interlocking knotted weft thread for overall weaving. The inner and outer layers are tightly interwoven, forming a stress-resistant whole that resists shear and deformation. Parameter Limitations: Because the inner and outer warp threads must share the same set of weft knots, the ratio of the outer main warp to the inner drug-loaded warp is strictly limited to 1:1. Advantageous Scenarios: When the drug loading reaches its maximum limit, it is suitable for the reconstruction of large wounds with severe contamination or extremely high risk of infection.

[0063] In summary, this embodiment is suitable for reconstruction patches for large wounds after bone tumor resection with a very high risk of local infection (or where mild infection already exists). A "co-weft integral braided structure" is employed. The outer main warp (0.5mm PET multifilament) and the inner drug-loaded warp (0.5mm core-skin structure) are strictly alternated in a 1:1 ratio. Both share a set of knotted weft threads (0.15mm) for integral braiding, and the knots are locked by a third warp thread (0.2mm). Simultaneously, the cross-sectional area ratio of the PET skin layer to the inner core layer of the inner drug-loaded warp is strictly controlled at 1:2.

[0064] Clinical advantages: This embodiment maximizes the density of drug-loaded warp lines (up to 50%), and the release concentrations of PLGA (LA:GA=50:50) and triclosan reach their peak within 4-6 weeks post-surgery, providing the most potent local antibacterial zone. It sacrifices some of the ultimate mechanical properties in exchange for absolute anti-infection safety.

[0065] Example 2:

[0066] This embodiment is no different from Embodiment 1 at the microscopic level, but there are differences in the macroscopic structure. See Appendix for details. Figure 5 and attached Figure 1 Compare the differences.

[0067] Appendix Figure 5 This diagram illustrates the independent oblique latitude suspension anchorage of an anti-infective core-loaded drug-inspired biomimetic artificial ligament patch from a "lateral" perspective. It shows the independent oblique latitude suspension anchorage structure.

[0068] In this embodiment, the weft yarn is an independent oblique weft yarn 6 without elasticity. The independent oblique weft yarn 6 forms a weaving node with the inner drug-carrying warp yarn 3 on the inner side and is fixedly connected to the selected outer main warp yarn 1 on the outer side. At least one of the selected outer main warp yarns 1 is not connected to the independent oblique weft yarn 6. Adjacent outer main warp yarns 1 are also connected by a wavy outer knotted weft yarn 5 to form a weaving structure. The whole structure forms a three-dimensional spatial decoupled weaving structure.

[0069] Independent oblique weft threads 6 serve as anchoring bridges between the inner and outer layers: To achieve spatial connection between the inner and outer layers, inelastic medical-grade PET fibers (preferably multifilament structure, with a diameter controlled between 0.1-0.2 mm) are used. The independent oblique weft threads 6 intersect obliquely (such as in a Z-shape or cross shape) in three-dimensional space, specifically for physically connecting the inner drug-loaded warp threads of the bottom layer with the outer main warp threads.

[0070] In this embodiment, unlike Embodiment 1, an independent inelastic PET weft thread is introduced along the Z-axis (thickness direction) spatial topology. This weft thread does not participate in the wavy knotting of the outer skeleton, but instead interweaves obliquely (or in a Z-shape) along the Z-axis, specifically for physically connecting and anchoring the inner drug-loaded warp threads to the nodes of the outer main skeleton. This independent Z-axis connection structure restricts the relative slippage of the inner and outer fibers during severe deformation, further preventing direct friction between the drug-loaded fibers and the outer skeleton from a physical structural perspective.

[0071] Inner and outer space connection and arrangement mechanism:

[0072] Corresponding to the co-weft integral knitting structure in this embodiment, Figure 5 Connection Mechanism: The outer principal warp lines are fixed by continuously knotted weft threads (providing the overall patch with shear and deformation buffering capabilities); while the inner drug-loaded warp lines are unidirectionally suspended and anchored to the outer principal warp lines via independent oblique weft threads. These oblique weft threads only act as bridges for fixed spatial distances and do not participate in the knotting, thus achieving physical decoupling (decoupling) of the forces on the inner and outer layers. Parameter Limitations: Thanks to the independent oblique weft suspension design, the arrangement of the inner drug-loaded warp lines is no longer subject to the forced constraints of the outer knotted nodes. Therefore, the ratio of the outer principal warp lines to the inner drug-loaded warp lines can be flexibly set to various ratios such as 2:1, 3:1, or 4:1. Advantageous Scenarios: It perfectly protects the drug-loaded layer from mechanical friction, and the proportion of pure mechanical fibers can be significantly increased by adjusting the ratio (e.g., 3:1), making it suitable for conventional large-segment defect reconstruction with extremely high requirements for joint high-frequency activity and force.

[0073] This embodiment is applicable to artificial ligament patches used after conventional bone tumor prosthesis replacement in situations requiring high-frequency joint stress. It employs an "independent oblique latitude suspension anchoring structure." The lateral principal meridian and the medial drug-loaded meridian are arranged in a 3:1 ratio. The lateral structure consists of a high-strength, purely mechanical framework formed by the principal meridian, knotted latitude lines, and a third meridian; the medial drug-loaded meridian is unidirectionally suspended and anchored below the lateral framework using "independent, inelastic oblique latitude lines." Simultaneously, the cross-sectional area ratio of the PET skin layer to the inner core layer of the medial drug-loaded meridian is controlled at 1:1. Clinical advantages: The pure mechanical fiber content is over 75%, sufficient to withstand the high-frequency flexion and extension shear forces of the knee / hip joint. Furthermore, the suspension anchoring design decouples the stress on the inner and outer layers, perfectly protecting the underlying drug-loaded meridian from mechanical tension and ensuring stable and sustained drug release. The pore size is strictly controlled between 100-300μm, perfectly adapting to the intraoperative infiltration and anchoring of bone cement.

[0074] The above two embodiments are optional embodiments of the present invention. Those skilled in the art can make various changes or improvements on this basis. Without departing from the general concept of the present invention, these changes or improvements should fall within the scope of protection claimed by the present invention.

Claims

1. A drug-eluting, biomimetic artificial ligament patch with an anti-infective core, characterized in that: Employs a multi-layered, spatially dense woven structure; The multi-layered spatial dense braided structure includes: Multiple parallel outer main meridians (1) and multiple parallel inner drug-carrying meridians (3); The outer main meridian (1) and the inner drug-carrying meridian (3) are interwoven through a weft system to form a whole; The inner drug-carrying warp (3) adopts a core-skin permeation controlled release structure, which has a drug-carrying matrix core layer and a drug sustained-release skin layer; the drug sustained-release skin layer is woven from multiple strands of polymer filaments and uses the physical gaps between the filaments as drug release channels.

2. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 1, characterized in that: The latitude system is a wavy latitude system, and the outer main meridian (1) and the inner drug-carrying meridian (3) are connected by wavy latitude systems that intersect vertically to form a whole. The multi-layered spatial dense weave structure also includes at least one set of straight third warp threads (4) that are parallel to each other. The at least one set of straight third warp threads (4) are longitudinally inserted into the multi-layered spatial dense weave structure and interwoven and locked with the wavy weft threads for reinforcement.

3. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 1, characterized in that: The drug-loaded matrix core layer is made of polylactic acid-glycolic acid copolymer, and the drug sustained-release skin layer is made of medical-grade PET polymer layer; the polylactic acid-glycolic acid copolymer is a blend matrix of LA (lactic acid):GA (glycolic acid) in a molar ratio of 50:50 and triclosan.

4. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 1, characterized in that: The ratio of the cross-sectional area of ​​the drug-releasing outer layer to the drug-loaded matrix core layer is 4:1 to 1:2, preferably 1:1 or 1:

2. Structurally, the drug-releasing outer layer completely encapsulates the drug-loaded matrix core layer, isolating it from direct mechanical friction. Mechanistically, the physical gaps naturally existing during the weaving of the outer multi-strand PET filaments serve as drug release channels, limiting the rate of water penetration and drug dissolution, eliminating burst release, while the high-strength PET outer layer withstands external mechanical friction, preventing the internal drug core from being physically scraped away.

5. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 2, characterized in that: The wavy weft is made of knotted weft (2) with elasticity. The outer main warp (1) and the inner medicine-carrying warp (3) form weaving nodes with the knotted weft (2) at the wavy bend of the knotted weft (2) to form a planar matrix alternating arrangement structure.

6. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 5, characterized in that: The planar matrix alternating arrangement structure: On the unfolded plane, the outer main warp (1) and the inner drug-carrying warp (3) are periodically arranged in parallel alternation at a ratio of 1:1, 2:1, 3:1 or 4:1, and the outer diameters of both are consistent, both being 0.4-1.2mm; Through this dense interweaving of high-strength pure PET fibers, the ultimate tensile load of the overall patch is shared in the structure.

7. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 1, characterized in that: The weft system uses independent oblique wefts (6) without elasticity. The independent oblique wefts (6) form a weaving node with the inner drug-carrying warp (3) on the inside and are fixedly connected to the selected outer main warp (1) on the outside. At least one of the selected outer main warp (1) is not connected to the independent oblique weft (6). The adjacent outer main warp (1) are also woven together by wavy outer knotted weft (5); The whole structure forms a three-dimensional spatially decoupled woven structure.

8. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 7, characterized in that: The three-dimensional spatial decoupled braiding structure introduces independent inelastic PET weft yarns as independent oblique weft yarns (6) in the spatial topology of the ligament patch thickness direction. These independent oblique weft yarns (6) do not participate in the outer wavy knot, but instead interweave in a Z-shape along the Z-axis, specifically used to physically connect and anchor the inner drug-loaded warp yarns to the nodes of the outer main skeleton. Through the independent oblique weft yarns (6), the relative slippage of the inner and outer fibers during severe deformation is restricted, thus avoiding direct friction between the drug-loaded fibers and the outer skeleton from a physical structure perspective.

9. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 1, characterized in that: The pore size of the three-dimensional mesh of the multi-layered spatial dense woven structure is maintained between 100 and 300 μm to facilitate intraoperative bone cement anchoring and postoperative fibroblast ingrowth.

10. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 2, characterized in that: The outer main warp (1) serves as the load-bearing skeleton and adopts a multi-strand twisted structure, consisting of 3-5 strands of PET multifilament twisted together. Each multifilament has a specification of 200D-400D (denier), and the diameter of the outer main warp (1) is controlled at 0.4-1.2mm. The wavy weft yarn adopts a fine multifilament structure, consisting of 1-2 strands of PET multifilament, with specifications of 100D-150D and a main diameter controlled at 0.2-1.0mm; in order to avoid the fine yarn from producing a "cutting effect" on the outer main warp (1), the ratio of the diameter of the wavy weft yarn to the diameter of the outer main warp (1) is 1:2 to 1:1, so as to increase the contact area and disperse the lateral shear force during high-frequency joint movement; The straight third meridian (4) realizes the straight insertion and locking of the wavy weft knot. It also adopts PET multifilament structure, with 1-3 strands of multifilament with specifications of 100D-200D twisted per strand, and the wire diameter is controlled at 0.2-0.6mm.

11. The anti-infective core-loaded drug-eluting biomimetic artificial ligament patch as described in claim 7, characterized in that: To achieve spatial connection between the inner and outer layers, the independent oblique weft (6) is made of inelastic medical-grade PET fiber with a multifilament structure and a wire diameter controlled at 0.1-0.2 mm. The independent oblique weft (6) is obliquely interwoven in a Z-shape or cross shape in three-dimensional space, and is specifically used to physically connect the inner drug-carrying warp (3) with the outer main warp (1).

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