3D printing tenon-mortise composite drug-loaded femoral head necrosis reconstruction rod and preparation method thereof

Abstract

This invention relates to the field of orthopedic repair technology, and provides a 3D-printed mortise-and-tenon composite drug-loaded femoral head necrosis reconstruction rod and its preparation method. The reconstruction rod includes a skeleton, the inner cavity of which has a three-dimensional, interconnected, micron-scale topological porous structure; both the outer surface of the skeleton and the surface of the micron-scale topological porous structure are covered with a drug composite layer; the outer surface of the skeleton has multiple tenons for forming a mortise-and-tenon lock with the inner wall of the femoral head medullary cavity; the drug composite layer contains a first drug that inhibits osteoclast activity and a second drug that promotes osteoblast differentiation. This invention achieves anti-rotation and anti-settlement mechanical locking with the host bone through a biomimetic mortise-and-tenon structure, and actively regulates the local bone repair microenvironment by loading dual drugs that inhibit osteoclast activity and promote osteoblast differentiation, ultimately achieving bio-integrated fixation mimicking natural bone.

Description

Technical Field

[0001] This invention relates to the field of orthopedic repair technology, and in particular to a 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod and its preparation method. Background Technology

[0002] Osteonecrosis of the femoral head (ONFH) is a common and refractory orthopedic disease, predominantly affecting young and middle-aged adults. Without timely intervention, it often leads to femoral head collapse, loss of joint function, and ultimately, total hip replacement. For early-stage, non-collapsed ONFH, reconstruction therapy that preserves the autologous femoral head is the preferred clinical approach. Among these treatments, intramedullary support rod implantation has received widespread attention due to its ability to provide mechanical support and promote bone repair.

[0003] Existing reconstruction rods are mostly solid or simple porous structures made of titanium alloy, and are prepared by turning or conventional selective laser melting (SLM) technology.

[0004] However, existing technologies have the following shortcomings: First, the interface integration between the reconstruction rod and the host bone mainly relies on bone ingrowth, lacking the synergistic effect of mechanical locking and biological fixation, making it prone to micromovement and loosening; Second, the reconstruction rod cannot be pharmacologically regulated to target the local microenvironment of femoral head necrosis (enhanced osteoclast activity and insufficient osteogenic capacity), making it difficult to effectively reverse the imbalance of bone repair; Third, the implantation position and direction of existing reconstruction rods rely on intraoperative experience judgment, making it difficult to achieve precise matching with the individualized necrotic area of ​​the patient; Fourth, the surface of traditional connection structures is smooth, making it difficult for bone cells to directly attach and form a firm biological fixation. Summary of the Invention

[0005] To overcome or alleviate one or more of the above technical problems, the present invention aims to provide a 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod and its preparation method. The reconstruction rod achieves anti-rotation and anti-settlement mechanical locking with the host bone through a biomimetic tenon-and-mortise structure. At the same time, by loading dual drugs that inhibit osteoclasts and promote osteogenic formation, it actively regulates the local bone repair microenvironment, and finally achieves bio-integrated fixation that mimics natural bone.

[0006] This invention provides the following technical solution:

[0007] On one hand, the present invention provides a 3D printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod, which includes a skeleton, wherein the inner cavity of the skeleton is provided with a three-dimensional through-hole micron-scale topological porous structure; the outer surface of the skeleton and the surface of the micron-scale topological porous structure are both covered with a drug composite layer.

[0008] The outer surface of the skeleton is provided with multiple tenons for forming a tenon-and-mortise lock with the mortise and tenon joints of the inner wall of the femoral head medullary cavity; the drug composite layer contains a first drug that inhibits osteoclast activity and a second drug that promotes osteoblast differentiation.

[0009] According to some possible implementations, the tenon surface is provided with a micron-scale array of micro-protrusions.

[0010] According to some possible implementations, the tenon has a trapezoidal, dovetail, or semi-circular cross-section; the tenons are distributed along the axial direction of the skeleton, the spacing between adjacent tenons is 3-10 mm, the tenon width is 1-3 mm, and the depth is 1-2 mm; the micro-protrusions are hemispherical, conical, or frustum-shaped, with a protrusion height of 50-200 micrometers, and the spacing between adjacent micro-protrusions is 30-100 micrometers, forming a continuous slit into which osteocytes can extend.

[0011] According to some possible implementations, the porosity of the topological porous structure is 60% to 85%, and the pore size is 200 to 600 micrometers.

[0012] According to some possible implementations, the first drug is zoledronic acid or denosumab, and the second drug is bone morphogenetic protein-2 or teriparatide.

[0013] According to some possible implementations, the skeleton is made of Ti-6Al-4V or Ti-6Al-7Nb.

[0014] Secondly, the present invention provides a method for preparing the 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod as described above, which includes the following steps:

[0015] S1. Obtain a three-dimensional model of the patient's femoral head necrosis area: Obtain CT or MRI data of the patient's hip joint through medical imaging equipment, reconstruct a three-dimensional model of the femoral head and necrosis area, and determine the implantation path and tenon-and-mortise mating position of the reconstruction rod.

[0016] S2. Design a customized mortise and tenon structure reconstruction rod model: In the 3D modeling software, based on the implantation path and necrotic area morphology determined in step S1, design the skeleton, design multiple tenons along the axial direction on its outer surface, and design a micron-level array of micro-protrusions on the surface of each tenon. At the same time, in the virtual model of the femoral head medullary cavity, design the mortises at the positions corresponding to the tenons to obtain the reconstruction rod model.

[0017] S3, SLM forming titanium alloy tenon and mortise structure reconstruction rod skeleton: Using selective laser melting technology, titanium alloy powder is used as raw material, and the reconstruction rod model designed in step S2 is 3D printed to obtain a skeleton with tenons, micro-protrusion array on the tenon surface and a topological porous structure inside.

[0018] S4. Composite drug loading: The skeleton obtained in step S3 is subjected to surface activation treatment, and then sequentially immersed in a solution containing a first drug and a solution containing a second drug. After vacuum impregnation and drying, the drug is loaded onto the inner wall of the micropores of the topological porous structure and the outer surface of the skeleton.

[0019] According to some possible implementations, the process parameters of the selective laser melting technology in step S3 are: laser power 80~150W, scanning speed 600~1200 mm / s, slice height 0.02~0.06 mm, and scanning spacing 0.08~0.15 mm.

[0020] According to some possible implementations, in step S4, the first drug solution is an aqueous solution of zoledronic acid with a concentration of 0.1~1.0 mg / mL; the second drug solution is BMP-2 phosphate buffer with a concentration of 50~200 mg / mL.

[0021] According to some possible implementations, the vacuum impregnation time in step S4 is 10 to 30 minutes, and the drying includes room temperature drying or freeze drying.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. This invention achieves mechanical locking between the reconstruction rod and the host bone through a mortise and tenon structure, which significantly improves the anti-rotation and anti-settlement capabilities and avoids the micromotion problem after implantation of traditional cylindrical reconstruction rods.

[0024] 2. The micron-level micro-protrusion array on the tenon surface forms a continuous bone cell invasion gap, allowing bone cells to grow deep inside, transforming the traditional "surface-to-surface" contact into a "three-dimensional interlaced" contact, achieving synergistic enhancement of mechanical fixation and biological fixation.

[0025] 3. The three-dimensional interconnected micropores inside the reconstruction rod provide a scaffold for bone tissue ingrowth and also serve as a drug reservoir to achieve local sustained release, inhibit osteoclast activity and promote osteoblast differentiation, thus synergistically improving the bone repair capacity of the femoral head necrosis area.

[0026] 4. Based on the patient's imaging data, the mortise and tenon positions and reconstruction rod shape are customized and designed. Combined with 3D printed surgical guides, precise implantation can be achieved, shortening the operation time and improving the treatment effect.

[0027] 5. This invention organically combines mechanical fixation (mortise and tenon joints), biological fixation (bone cells invading the gaps of micro-protrusions + bone ingrowth into porous structures) and drug regulation (anti-bone resorption + bone-promoting) to form a "natural bone-integrated fixation" strategy, providing a new solution for hip-preserving treatment of femoral head necrosis. Attached Figure Description

[0028] FIG. 1A This is a schematic diagram of a 3D-printed mortise and tenon composite drug-loaded femoral head necrosis reconstruction rod with tenons distributed in the middle of the skeleton, as provided in an embodiment of the present invention.

[0029] FIG. 1B This is a schematic diagram of a 3D-printed mortise and tenon composite drug-loaded femoral head necrosis reconstruction rod with tenons distributed at one end of the skeleton, as provided in an embodiment of the present invention.

[0030] FIG. 1C This is a schematic diagram of a 3D-printed mortise and tenon composite drug-loaded femoral head necrosis reconstruction rod with tenons distributed in the middle and head of the skeleton, as provided in an embodiment of the present invention.

[0031] FIG. 1D This is a schematic diagram of a 3D-printed mortise and tenon composite drug-loaded femoral head necrosis reconstruction rod with tenons distributed on the entire outer surface of the skeleton, as provided in an embodiment of the present invention.

[0032] FIG. 2 This is a schematic diagram of the structure of a 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod implanted into the femoral head, as provided in an embodiment of the present invention.

[0033] FIG. 3 This is a partially enlarged schematic diagram of the junction between the skeleton and the femoral head, provided in an embodiment of the present invention.

[0034] FIG. 4 The image shows the drug release curve of the reconstruction rod in simulated body fluid, as provided in an embodiment of the present invention.

[0035] In the picture:

[0036] 1. Skeleton; 2. Tenon; 3. Topological porous structure. Detailed Implementation

[0037] This invention provides a reconstruction rod that can achieve mechanical stability and fixation, actively regulate local bone metabolism, closely match the patient's anatomical structure, and induce bone cells to grow directly into the fixation interface. This is of great significance for improving the success rate of hip preservation treatment for avascular necrosis of the femoral head.

[0038] The technical concept of this invention is as follows: Based on the patient's preoperative CT or MRI data, a three-dimensional anatomical model of the femoral head necrosis area is reconstructed; a reconstruction rod with a tenon-and-mortise structure is designed, with multiple wedge-shaped or dovetail-shaped protrusions, i.e., tenons 2, set on the outer surface of the skeleton 1 (including the ends and / or the middle part). The tenons 2 match the pre-set mortises in the medullary cavity of the necrotic area to achieve anti-rotation and axial stability after implantation; micron-level gaps that can be penetrated by osteocytes are formed between adjacent tenons 2, allowing osteocytes to grow deep into them, thereby establishing a true biological locking interface in addition to mechanical locking; a topological porous structure 3 is designed inside the reconstruction rod, which is a micron-level three-dimensional interconnected microporous structure. "Three-dimensional interconnected" means that each micropore is interconnected with each other, rather than penetrating the outer surface of the skeleton 1; and drugs are loaded on the inner surface of the microporous structure and the outer surface of the reconstruction rod skeleton 1. The drugs include a first drug that inhibits osteoclast activity (such as zoledronic acid) and a second drug that promotes osteoblast differentiation (such as BMP-2); the titanium alloy tenon-and-mortise structure skeleton is integrally formed by SLM technology, and then drug loading is completed by solution impregnation or freeze-drying.

[0039] The present invention will now be described in detail with reference to embodiments and accompanying drawings. However, it should be understood that the embodiments and drawings are for illustrative purposes only and do not constitute any limitation on the scope of protection of the present invention. All reasonable modifications and combinations included within the inventive spirit of the present invention fall within the scope of protection of the present invention.

[0040] In the following embodiments, the selective laser melting equipment used is the Concept Laser MLab cusing R metal 3D printer from Germany, with a laser spot diameter of 50 micrometers and titanium alloy powder of Ti-6Al-4V, with a particle size range of 15~45 micrometers. The default process parameters of the equipment are: laser power 95W, scanning speed 900 mm / s, slice height 0.05 mm, and scanning spacing 0.10 mm.

[0041] Example 1

[0042] This embodiment describes the custom fabrication of a 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod, following the steps below:

[0043] (1) Obtain a three-dimensional model of the femoral head necrosis area in the patient.

[0044] Hip CT data (0.625 mm slice thickness) from a patient with early-stage femoral head necrosis were collected and imported into Mimics software to reconstruct a 3D model of the femoral head and necrotic area. The necrotic area was determined to be located on the anterolateral aspect of the femoral head. The planned implantation path was through the femoral neck to the necrotic area. The tenon-and-mortise joint was positioned 5 mm from the subchondral bone of the femoral head on the medullary canal wall. FIG. 2 ;

[0045] (2) Design a custom-made mortise and tenon structure reconstruction rod model

[0046] In Solidworks software, the skeleton 1 is designed as a cylindrical shape with a diameter of 10 mm and a length of 35 mm. A series of dovetail tenons 2 are evenly distributed along the axial direction on its outer surface. The tenons 2 are 2 mm wide, 1.5 mm deep, and 5 mm apart. A hemispherical micro-protrusion array is designed on the surface of each tenon 2, with a protrusion height of 100 micrometers, a bottom diameter of 80 micrometers, and a spacing of 50 micrometers between adjacent protrusions. Mortises are designed at corresponding positions in the virtual model of the femoral head medullary cavity. The interior of the skeleton 1 is designed as a rhombic dodecahedral porous structure with a porosity of 75% and a pore size of 400 micrometers.

[0047] (3) SLM-formed titanium alloy tenon and mortise structure reconstruction rod skeleton

[0048] The reconstruction rod model (without drugs) designed in step (2) was imported into the layer slicing software. The slice height was set to 0.05 mm. SLM was performed using a laser power of 95 W, a scanning speed of 900 mm / s, and a scanning interval of 0.10 mm to obtain the titanium alloy skeleton 1.

[0049] (4) Composite drug delivery

[0050] The skeleton 1 obtained in step (3) was ultrasonically cleaned with anhydrous ethanol and deionized water for 10 minutes each, dried, and then subjected to oxygen plasma surface treatment for 5 minutes. Then it was immersed in an aqueous solution containing 0.5 mg / mL zoledronic acid and vacuum-impregnated for 20 minutes. It was then removed and dried at room temperature. Next, it was immersed in a PBS solution containing 100 µm / mL BMP-2 and vacuum-impregnated for 20 minutes. Finally, it was freeze-dried for 12 hours to obtain the final product.

[0051] The macroscopic structure of the reconstruction rod prepared in this embodiment is as follows: FIG. 1D As shown, tenon 2 completely covers the outer surface of skeleton 1. FIGS. 1A-1D A diagram showing the distribution of different tenon 2 locations. FIG. 1A In the left image, tenon 2 is located in the middle of frame 1. FIG. 1B The middle tenon 2 is located at the head of the skeleton 1. FIG. 1C The middle tenon 2 is located at the head and the middle respectively. FIG. 1D The tenons 2 are distributed on the overall outer surface of the skeleton 1.

[0052] The microstructure of topological porous structure 3 is as follows FIG. 1A The right image and FIG. 3 As shown, FIG. 3 In the diagram, the gray tooth-like structure represents the tenon 2 on the outer surface of the skeleton 1, and the yellow mesh structure represents the grown bone tissue, used to show the state of mechanical locking and bone ingrowth fixation between the reconstruction rod and the bone tissue after implantation.

[0053] Example 2

[0054] This embodiment is basically the same as embodiment 1, except that: in step (2), the micro-protrusion on the surface of the tenon 2 is conical (height 150µm, bottom diameter 100µm, spacing 80µm), the porosity of the topological porous structure 3 is 70%, and the pore size is 350µm; in step (4), the first drug is denosumab (concentration 0.2 mg / mL), and the second drug is teriparatide (concentration 150µg / mL).

[0055] The resulting reconstructed rod has a good tenon-and-mortise fit, the micro-protrusions on the surface of the tenon 2 are clearly visible, and the drug load is uniform.

[0056] Example 3

[0057] This embodiment is basically the same as embodiment 1, except that: in step (2), the micro-protrusion on the surface of the tenon 2 is frustum-shaped (height 80µm, top side length 40µm, bottom side length 60µm, spacing 40µm), the porous structure has a porosity of 80% and a pore diameter of 500µm; in step (4), the first drug concentration is 0.8 mg / mL zoledronic acid, and the second drug concentration is 180µg / mL BMP-2.

[0058] The resulting reconstruction rod has more mechanical locking points, further improving its anti-rotation performance.

[0059] Example 4

[0060] This embodiment is basically the same as embodiment 1, except that: in step (2), the porosity of the internal topological porous structure 3 is 60% and the pore size is 200µm; in step (3), the SLM process parameters are: laser power 80W, scanning speed 600 mm / s, slice height 0.04 mm, and scanning spacing 0.08 mm.

[0061] The resulting reconstruction rod has high mechanical strength and is suitable for cases requiring greater load-bearing capacity.

[0062] Example 5

[0063] This embodiment is basically the same as embodiment 1, except that: in step (2), the porosity of the internal topological porous structure 3 is 85% and the pore size is 600µm; in step (3), the SLM process parameters are: laser power 150W, scanning speed 1200 mm / s, slice height 0.06 mm, and scanning spacing 0.15 mm.

[0064] The resulting reconstruction rod has higher porosity, which is beneficial for drug loading and bone tissue ingrowth.

[0065] Example 6

[0066] This embodiment is basically the same as embodiment 1, except that: in step (2), the internal porous structure is a cubic hole unit with a porosity of 70% and a hole diameter of 300µm; the height of the micro protrusions on the surface of the tenon 2 is 50µm and the spacing is 30µm.

[0067] The resulting reconstructed rod has a regular pore structure and balanced mechanical and osteogenic properties.

[0068] Example 7

[0069] This embodiment is basically the same as that of embodiment 1, except that: in step (2), the length of the reconstruction rod is 30 mm and the diameter is 8 mm, the height of the micro-protrusion on the surface of the tenon 2 is 120 µm and the spacing is 60 µm; in step (4), the first drug is zoledronic acid (concentration 0.3 mg / mL) and the second drug is BMP-2 (concentration 80 µg / mL).

[0070] The resulting reconstruction rod is suitable for cases with a small area of ​​necrosis.

[0071] Example 8

[0072] This embodiment is basically the same as that of embodiment 1, except that: in step (2), the length of the reconstruction rod is 40 mm and the diameter is 12 mm, the height of the micro-protrusion on the surface of the tenon 2 is 180 µm and the spacing is 90 µm; in step (4), the first drug is denosumab (concentration 0.6 mg / mL) and the second drug is teriparatide (concentration 120 µg / mL).

[0073] The resulting reconstruction rod is suitable for cases with a large area of ​​necrosis.

[0074] Example 9

[0075] This embodiment is basically the same as embodiment 1, except that: in step (2), the cross-section of tenon 2 is trapezoidal (top base 1 mm, bottom base 2 mm, height 1.5 mm), and the micro-protrusion is hemispherical (height 60µm, spacing 40µm); in step (3), the SLM process parameters are: laser power 110W, scanning speed 750 mm / s, slice height 0.05 mm, scanning spacing 0.12 mm; in step (4), the vacuum impregnation time is 15 minutes.

[0076] The resulting reconstruction rod has high forming precision and stable tenon-and-mortise fit.

[0077] Example 10

[0078] This embodiment is basically the same as embodiment 1, except that: in step (2), the cross-section of tenon 2 is semi-circular (radius 1 mm), and the micro-protrusion is conical (height 200 µm, spacing 100 µm); in step (3), the titanium alloy powder is Ti-6Al-7Nb, and the process parameters are: laser power 130W, scanning speed 1000 mm / s, slice height 0.05 mm, scanning spacing 0.13 mm; in step (4), the first drug is zoledronic acid (concentration 1.0 mg / mL), the second drug is BMP-2 (concentration 200 µg / mL), and the vacuum impregnation time is 30 minutes.

[0079] The resulting reconstruction rods are made of different titanium alloy materials, which have better biocompatibility and are suitable for patients at risk of allergy to titanium alloys.

[0080] Comparative Example 1

[0081] The steps for preparing a traditional cylindrical reconstruction rod without mortise and tenon joints in this comparative example are as follows:

[0082] (1) Creating a model

[0083] A solid cylindrical model with a diameter of 10 mm and a length of 35 mm was created using modeling software. The model has no porous structure inside and no tenons or micro-protrusion array on the surface.

[0084] (2) Determine process parameters

[0085] The processing parameters were set as follows: laser power of 95W, scanning spacing of 0.10 mm, slice height of 0.05 mm, and scanning speed of 900 mm / s for the selective laser melting equipment used.

[0086] (3) Processing

[0087] Import the solid model created in step (1) into the layered slicing software and set the slice height to 0.05 mm. Obtain the processing path data and import it into the selective laser melting device. Input the determined laser power of 95W, scanning speed of 900 mm / s and scanning spacing of 0.10 mm into the selective laser melting device. Use Ti-6Al-4V powder as raw material for processing to obtain a traditional solid cylindrical reconstruction rod without drug loading.

[0088] The product of Comparative Example 1 has a smooth surface, no mortise and tenon structure, and no internal pores, and therefore cannot provide mechanical locking and drug sustained release functions.

[0089] Comparative Example 2

[0090] The comparative example prepared a reconstruction rod with a mortise and tenon structure but with a smooth surface (no micro-protrusion array) and no drug loading. The steps are as follows:

[0091] (1) Creating a model

[0092] A cylindrical model with a diameter of 10 mm and a length of 35 mm was created using modeling software. Multiple dovetail tenons 2 (tenon 2 width 2 mm, depth 1.5 mm, spacing 5 mm) are evenly distributed along the axial direction on the outer surface. The surface of tenon 2 is smooth without micro-protrusion array and has no porous structure inside.

[0093] (2) Determine process parameters

[0094] The processing parameters were set as follows: laser power of 95W, scanning spacing of 0.10 mm, slice height of 0.05 mm, and scanning speed of 900 mm / s for the selective laser melting equipment used.

[0095] (3) Processing

[0096] The model created in step (1) is imported into the layered slicing software and the slice height is set to 0.05 mm. The processing path data is obtained and imported into the selective laser melting device. The determined laser power of 95W, scanning speed of 900 mm / s and scanning spacing of 0.10 mm are input into the selective laser melting device. Ti-6Al-4V powder is used as raw material for processing to obtain a reconstruction rod with a mortise and tenon structure but a smooth surface. No drug loading treatment is performed.

[0097] The product obtained in Comparative Example 2 has mechanical locking capability, but lacks biological locking interface and drug regulation function.

[0098] Comparative Example 3

[0099] This comparative example prepares a reconstruction rod with a mortise and tenon structure and an array of micro-protrusions on the tenon surface, but without an internal porous structure and without drug loading. The steps are as follows:

[0100] (1) Creating a model

[0101] A cylindrical model with a diameter of 10 mm and a length of 35 mm was created using modeling software. Multiple dovetail tenons 2 are distributed equidistantly along the axial direction on the outer surface. Each tenon 2 has a hemispherical micro-protrusion array (protrusion height 100 µm, spacing 50 µm) on its surface. The interior is a solid structure without any porous structure.

[0102] (2) Determine process parameters

[0103] The processing parameters were set as follows: laser power of 95W, scanning spacing of 0.10 mm, slice height of 0.05 mm, and scanning speed of 900 mm / s for the selective laser melting equipment used.

[0104] (3) Processing

[0105] The model created in step (1) is imported into the layered slicing software and the slicing height is set to 0.05 mm. The processing path data is obtained and imported into the selective laser melting device. The determined laser power of 95W, scanning speed of 900 mm / s and scanning spacing of 0.10 mm are input into the selective laser melting device. Ti-6Al-4V powder is used as raw material for processing to obtain a reconstruction rod with mortise and tenon structure and micro-protrusion array on the surface of the tenon 2 but solid inside. No drug loading treatment is performed.

[0106] The resulting Comparative Example 3 product has mechanical and biological locking capabilities, but lacks drug release function and bone ingrowth space.

[0107] Performance Testing and Comparison

[0108] The reconstruction rods prepared in Examples 1-10 and Comparative Examples 1-3 were subjected to the following performance tests:

[0109] 1. Mechanical property testing

[0110] The compressive strength and rotational torque of the reconstruction rod were tested using a universal testing machine. The results showed that the compressive strength of Example 1 was 85.6 ± 5.2 MPa, and the rotational torque was 2.35 ± 0.18 N·m; the rotational torque of Comparative Example 1 (without tenon) was only 0.82 ± 0.09 N·m, which was 65.1% lower than that of Example 1; the rotational torques of Comparative Example 2 (smooth tenon 2) and Comparative Example 3 (with micro-protrusion) were 2.28 ± 0.15 N·m and 2.31 ± 0.16 N·m, respectively, which were not significantly different from those of Example 1, indicating that the tenon structure is the main contributing factor to mechanical locking.

[0111] 2. Cell adhesion and proliferation experiments

[0112] Rat bone marrow mesenchymal stem cells were seeded onto the surface of reconstruction rods in each example and comparative example, and DNA quantification was performed after 7 days of culture. The results showed that the number of cells adhering in Example 1 was 4.2 times that of Comparative Example 1 and 2.8 times that of Comparative Example 2; the number of cells in Comparative Example 3 (with micro-protrusions, without pores) was 1.9 times that of Comparative Example 2, indicating that the micro-protrusion array on the surface of tenon 2 significantly promoted cell adhesion.

[0113] 3. Osteogenic Differentiation Detection

[0114] After 14 days of culture, alkaline phosphatase (ALP) activity was measured. The results showed that the ALP activity of Example 1 was 3.5 times that of Comparative Example 1, 2.2 times that of Comparative Example 2, and 1.4 times that of Comparative Example 3. Among Examples 1 to 10, Examples 3 and 5, which had higher porosity, showed higher ALP activity.

[0115] 4. Drug release curve

[0116] The reconstruction rods from Examples 1-10 were immersed in simulated body fluid, and the drug release rate was determined using high-performance liquid chromatography (HPLC). The results are as follows: FIG. 4 As shown: All examples exhibited an initial burst release (20-30% release within 24 hours) followed by a steady release over the next 28 days, with a cumulative release rate of 70-80%. The drug release curve of Example 1 was the most stable, while in Examples 2 and 8, due to the larger molecular weights of denosumab and teriparatide, the release rates were slightly slower.

[0117] 5. Animal experiments

[0118] The reconstruction rods from Examples 1, 1, 2, and 3 were implanted into rabbit femoral head necrosis models (n=6 in each group). Micro-CT and histological analysis were performed 8 weeks post-surgery. Results showed:

[0119] Example 1 group: Continuous new bone formation was visible between the reconstruction rod and the host bone, with a bone integration rate (bone-implant contact percentage) of 78±6%. A large number of osteocytes were visible in the gaps of the micro-protrusions on the surface of tenon 2, and the porous structure was filled with newly formed bone tissue.

[0120] Comparative Example 1: The reconstruction rod was surrounded by fibrous tissue, with an osteointegration rate of only 15±4%, and obvious micromotion gaps were visible.

[0121] Comparative Example 2: The mortise and tenon structure provides mechanical stability, but there is no direct contact between bone cells and the surface of the tenon 2, the bone integration rate is 42±5%, and fibrous tissue gaps are visible at the interface.

[0122] Comparative Example 3: Osteocytes invaded the gaps in the micro-protrusions on the surface of tenon 2, but the solid internal structure could not provide space for bone ingrowth, and the bone integration rate was 55±6%.

[0123] The above results indicate that the reconstruction rod of the present invention (Examples 1-10) provides mechanical locking through the tenon and mortise structure, provides biological locking by inducing osteoblast invasion through the micro-protrusion array on the surface of the tenon 2, and provides bone ingrowth space and drug regulation through the internal porous structure and drug loading. The three aspects work together to achieve the optimal osteointegration effect.

[0124] The above embodiments are merely preferred embodiments of the present invention, and the scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod, characterized in that: The system includes a framework, the inner cavity of which has a three-dimensional, through-hole micron-scale topological porous structure; both the outer surface of the framework and the surface of the micron-scale topological porous structure are coated with a drug composite layer. The outer surface of the skeleton is provided with multiple tenons for forming a tenon-and-mortise lock with the mortise and tenon joints of the inner wall of the femoral head medullary cavity; the drug composite layer contains a first drug that inhibits osteoclast activity and a second drug that promotes osteoblast differentiation.

2. The 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod according to claim 1, characterized in that: The tenon surface is provided with a micron-scale array of micro-protrusions.

3. The 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod according to claim 2, characterized in that: The tenon has a trapezoidal, dovetail, or semi-circular cross-section; the tenons are distributed along the axial direction of the skeleton, with a spacing of 3-10 mm between adjacent tenons, a tenon width of 1-3 mm, and a depth of 1-2 mm; the micro-protrusions are hemispherical, conical, or frustum-shaped, with a protrusion height of 50-200 micrometers, and a spacing of 30-100 micrometers between adjacent micro-protrusions, forming a continuous slit into which bone cell pseudopodia can extend.

4. The 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod according to claim 1, characterized in that: The porosity of the topological porous structure is 60%~85%, and the pore size is 200~600 micrometers.

5. The 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod according to claim 1, characterized in that: The first drug is zoledronic acid or denosumab, and the second drug is bone morphogenetic protein-2 or teriparatide.

6. The 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod according to claim 1, characterized in that: The skeleton is made of Ti-6Al-4V or Ti-6Al-7Nb.

7. A method for preparing a 3D-printed tenon-and-mortise composite drug-loaded femoral head necrosis reconstruction rod as described in any one of claims 2 to 6, characterized in that: Includes the following steps: S1. Obtain a 3D model of the area of ​​femoral head necrosis in the patient: CT or MRI data of the patient's hip joint are obtained through medical imaging equipment, a three-dimensional model of the femoral head and necrotic area is reconstructed, and the implantation path and tenon-and-mortise mating position of the reconstruction rod are determined. S2. Design a custom-made mortise and tenon structure reconstruction rod model: In the 3D modeling software, the skeleton is designed according to the implantation path and necrotic area morphology determined in step S1. Multiple tenons are designed along the axial direction on its outer surface, and a micron-level array of micro-protrusions is designed on the surface of each tenon. At the same time, mortises are designed at the positions corresponding to the tenons in the virtual model of the femoral head medullary cavity to obtain the reconstruction rod model. S3, SLM molded titanium alloy tenon and mortise structure reconstruction rod skeleton: Using selective laser melting technology, titanium alloy powder was used as raw material to 3D print the reconstruction rod model designed in step S2, resulting in a skeleton with tenons, an array of micro-protrusions on the tenon surface, and a topologically porous structure inside. S4, Composite Drug Loading: The skeleton 1 obtained in step S3 is subjected to surface activation treatment, and then sequentially immersed in a solution containing the first drug and a solution containing the second drug. After vacuum impregnation and drying, the drug is loaded onto the inner wall of the micropores of the topological porous structure and the outer surface of the skeleton.

8. The preparation method according to claim 7, characterized in that: The process parameters of the selective laser melting technology described in step S3 are: laser power 80~150W, scanning speed 600~1200 mm / s, slice height 0.02~0.06 mm, and scanning spacing 0.08~0.15 mm.

9. The preparation method according to claim 7, characterized in that: In step S4, the first drug solution is an aqueous solution of zoledronic acid with a concentration of 0.1~1.0 mg / mL; the second drug solution is BMP-2 phosphate buffer with a concentration of 50~200 mg / mL.

10. The preparation method according to claim 7, characterized in that: The vacuum impregnation time in step S4 is 10-30 minutes, and the drying includes room temperature drying or freeze drying.

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