Special-shaped titanium alloy capable of enhancing bone regeneration and repair efficacy as well as preparation method and application of special-shaped titanium alloy

Abstract

The invention discloses a special-shaped titanium alloy capable of enhancing bone regeneration and repair efficacy as well as a preparation method and application of the special-shaped titanium alloy. The special-shaped titanium alloy comprises a special-shaped titanium alloy base body and a porous structure attached to the special-shaped titanium alloy base body, and the porous structure is in multi-stage size distribution and comprises long-strip-shaped gullies (100-150 micrometers wide) and large holes (30-50 micrometers wide). And the morphology in the gullies shows coralline ligaments and a nest-shaped pore channel (0.5-2 microns) structure. This can provide space and sites for the growth and adsorption of osteoblasts. According to the method, a gas phase alloying (VPA) and VPD synergistic process is adopted in a breakthrough mode, a non-oxidation / nitridation coralline-shaped hierarchical pore structure is constructed on the surface of the commercial titanium implant, and it can be achieved through verification of an aging animal model that a special-shaped matrix is uniformly modified in the whole domain, the regeneration function of aging stem cells is activated, and the bone repair and regeneration effect is effectively improved.

Description

Technical Field

[0001] This invention belongs to the fields of biomedicine and biomaterials technology, specifically relating to an irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy, its preparation method, and its application. Background Technology

[0002] The statements herein provide only background information in relation to this invention and do not necessarily constitute prior art.

[0003] The accelerating global aging process has led to a surge in age-related bone diseases, the pathological essence of which lies in the progressive destruction of bone homeostasis and the decline in regenerative function, becoming a core challenge of the modern medical system. Bone healing disorders, as a serious complication after orthopedic surgery, are characterized by chronic low-grade inflammation (inflammatory aging), accompanied by a decline in immune system function—particularly reflected in the macrophage population that regulates inflammatory homeostasis. Although immune regulation plays a crucial role in tissue repair (by delivering nutrient factors and activating endogenous stem cells to enhance cellular plasticity), stem cells residing in the bone defect microenvironment exhibit weakened regenerative potential and reduced differentiation capacity, and currently lack effective measures to regulate the regenerative and differentiation potential of stem cells.

[0004] Three-dimensional scaffolds with precise geometry, pore distribution, and porosity are crucial for addressing regenerative barriers, as they directly regulate nutrient diffusion, cell migration and differentiation, angiogenesis, and tissue regeneration rates. However, there are technical bottlenecks in the manipulation of the surface morphology of such heteromorphic implants: traditional processes struggle to achieve uniform modification of complex geometric surfaces, and scalable customized solutions are lacking.

[0005] While porous titanium (p-Ti) possesses excellent biocompatibility and mechanical properties, traditional pore-forming techniques (powder metallurgy, injection molding, additive manufacturing) have inherent limitations: complex processes and high costs, capable of constructing only simple pore structures, and unable to respond to the contextualized needs of biological systems. Key evidence suggests that: nerve cells preferentially penetrate pores rather than concave surfaces; mesenchymal stem cells tend to differentiate into chondrocytes within 90–120 μm pores; actin fibers aggregate in concave surfaces; pro-inflammatory factors accumulate in large-pore regions; angiogenesis occurs in concave areas; and macrophage infiltration and angiogenesis, essential for bone regeneration, depend on pores of 100–800 μm, which current technologies struggle to meet for their multidimensional synergistic requirements.

[0006] While vapor-phase dealloying (VPD) technology constructs porous structures through vapor pressure differences and has been successfully applied to metals such as copper and nickel, titanium matrices face the risk of oxidation / nitridation due to their high oxygen / nitrogen affinity. Current research largely focuses on the immune regulation of pore sizes in the 1–100 μm range, but lacks a systematic understanding of the cross-scale mechanisms of tissue repair. Summary of the Invention

[0007] To address the shortcomings of existing technologies, the purpose of this invention is to provide a shaped titanium alloy with enhanced bone regeneration and repair efficacy, its preparation method, and its applications. This invention proposes a vapor phase dealloying technique. This method precisely controls the selective etching of elements on the surface of the titanium matrix through a vapor-phase reaction, constructing a multi-level micro / nano porous structure (pore size gradient distribution of 1~100 μm) throughout the shaped implant, thus breaking through the challenge of achieving morphological uniformity in curved surfaces, pores, and angular regions.

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] As a first aspect of the present invention, a shaped titanium alloy with enhanced bone regeneration and repair efficacy is provided. The shaped titanium alloy comprises a shaped titanium alloy matrix and a porous structure attached to the matrix. The porous structure exhibits a multi-level size distribution, including elongated grooves (100-150 μm wide) and larger pores (30-50 μm). The morphology within the grooves displays coral-like ligaments and nest-like channels (0.5-2 μm). This provides space and sites for osteoblast growth and adsorption.

[0010] This invention utilizes vapor phase alloying (VPA) combined with vapor phase dealloying (VPD) to prepare an unoxidized and nitrided coral-like porous structure on irregularly shaped titanium alloy implants.

[0011] Secondly, the present invention provides a method for preparing an irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy, comprising the following steps: S1, Vapor phase alloying treatment of irregularly shaped titanium alloys: The irregularly shaped titanium alloy workpiece and the sacrificial metal are placed together in a low vacuum of 1~100 Pa and a high temperature of 600~800℃ for 1~15 hours to carry out vapor phase alloying (VPA) to obtain the precursor. In step S1, the sacrificial metal is zinc particles.

[0012] In step S1, vapor phase alloying is performed in a muffle furnace.

[0013] S2, Vapor phase dealloying treatment: Place the irregularly shaped titanium alloy precursor after the vapor phase alloying treatment in step S1 in a container and incubate at 550~750℃ for 1×10⁻⁶ days. -2 Vapor phase dealloying (VPD) is performed by holding the material at ~100 Pa for 1 to 2 hours.

[0014] In steps S1 and S2, a vapor-phase dealloying process is performed in a quartz tube.

[0015] In step S2, vapor-phase dealloying is performed in a tube furnace.

[0016] Furthermore, in step S2, titanium foil is placed on both sides of the titanium alloy in the container to ensure airtightness and to eliminate the influence of gases such as oxygen and nitrogen.

[0017] Furthermore, in step S2, an auxiliary gas is introduced into the quartz tube to further prevent sample oxidation during the dealloying process. The auxiliary gas is high-purity argon or an argon-hydrogen mixture.

[0018] This invention reveals that: First, thanks to its coral-like hierarchical structure with niche-like pores, porous titanium alloy (p-Ti) exhibits excellent osteogenic properties, promoting osteogenic differentiation and expression of bone marrow mesenchymal stem cells (BMMSCs). Second, by co-culturing p-Ti with macrophages, the bone immunomodulatory effects of p-Ti were further investigated in vitro. The coral-like hierarchical structure of p-Ti can promote ARG1... + Macrophage production. Furthermore, by establishing dual-validation bone defect models in aging rats and rabbits, the in vivo osseointegration and remodeling effects of p-Ti implants were further investigated.

[0019] The study also found that the irregular titanium alloy prepared by the present invention exhibits a multi-sized porous structure on its surface morphology, with obvious groove and pore structures. The porous structures of different sizes contain secondary ligament-channel structures, which are beneficial to the growth of osteoblasts.

[0020] Thirdly, the present invention provides the application of the aforementioned irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy in the preparation of bone implants.

[0021] The beneficial effects achieved by one or more embodiments of the present invention described above are as follows: 1. This invention innovatively employs a synergistic process of vapor phase alloying (VPA) and vapor phase dealloying (VPD) to construct a coral-like hierarchical porous structure on the surface of commercial titanium implants without oxidation / nitridation. Validated in aging animal models, this invention can achieve: uniform modification of the entire heterogeneous matrix and activation of the regenerative function of aging stem cells, effectively improving bone repair and regeneration.

[0022] 2. The irregular titanium alloy with enhanced bone regeneration and repair efficacy provided by the present invention has a secondary ligament-channel structure inside its porous structure, which is conducive to the growth of osteoblasts.

[0023] 3. The irregularly shaped titanium alloy provided by this invention, which enhances bone regeneration and repair efficacy, promotes osteogenic differentiation and expression of bone marrow mesenchymal stem cells (BMMSCs) and promotes ARG1. + The production of macrophages enables bone integration and reconstruction within the body.

[0024] 4. Compared with other technologies, the method for preparing irregularly shaped titanium alloys with enhanced bone regeneration and repair efficacy provided in this application can directly process existing implant workpieces, etc., without the need for redesigning methods such as powder sintering and 3D printing; secondly, this method can directly form multi-level pores on the surface, which is conducive to the adsorption of different cells and cell tails.

[0025] 5. The bone regeneration and repair titanium alloy provided by this invention, which has the effect of regulating macrophage aging, can effectively promote osteogenic differentiation and reverse macrophage aging in vitro, and has great potential to promote the regeneration of aging bone. Attached Figure Description

[0026] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0027] Figure 1 This is a characterization of the titanium raw material and porous titanium implant in Example 1; wherein, (a) a schematic diagram of the porous titanium preparation process, (b) a photograph of the p-Ti disk after VPD treatment, (c) the surface morphology of porous titanium, (d) the magnified morphology of porous titanium in the yellow area of ​​(c), (e) elemental content, (f) Zn release amount, (g) corrosion resistance comparison, and (h) X-ray diffraction pattern.

[0028] Figure 2 The effect of porous titanium prepared for Example 1 on osteogenic differentiation of rat BMMSCs; wherein, (ad) expression of ALP (alkaline phosphatase), OCN (osteocalcin), RUNX2 (Runt-related transcription factor 2) and COL1 (type I collagen) in rat BMMSCs in each implant group on day 2 of culture; (e) quantitative analysis by immunofluorescence staining: expression level of ALP in rat BMMSCs in each implant group on day 3 of culture; (f) immunofluorescence staining images: expression of ALP in rat BMMSCs in each implant group on day 3 of culture, with scale bars of 50 μm in the figures. This indicates that compared to the titanium group, P < 0.05. This indicates that P < 0.01 compared to the titanium group.

[0029] Figure 3The porous titanium prepared in Example 1 was used to regulate macrophage immune senescence and inhibit the secretion of inflammatory factors. Specifically, (ad) RT-PCR was used to detect the expression of iNOS, CD206, ARG1, and BMP2 in macrophages cultured on the porous titanium surface; (e) representative images of immunofluorescence staining of macrophage markers (iNOS and CD206) on the porous titanium surface; (fg) ELISA was used to detect the secretion levels of IL10 and IL6 in macrophages on the porous titanium surface on day 2 of culture; (h) Western blot quantitative analysis results; and (i) Western blot was used to detect the expression of CD163, IL1β, p16, and p21 in macrophages in the conditioned medium system. This indicates that compared to the titanium group, P < 0.05. This indicates that P < 0.01 compared to the titanium group.

[0030] Figure 4 The porous titanium implant prepared in Example 1 promotes osseointegration in a bone defect model; (a) actual image of the femoral specimen, (b) image of hard tissue sections stained with calcein / alizarin red double staining, where the scale bar is 200 μm, (c) quantitative analysis of femoral length in each group 8 weeks after implantation, (d) quantitative analysis of calcein-stained hard tissue sections, (e) representative H&E staining images of rat organs in different treatment groups, where the scale bar is 500 μm, (fi) quantitative analysis of bone volume fraction (BV / TV%), number of trabeculae (Tb.N), trabecular separation (Tb.Sp), and trabecular thickness (Tb.Th), and (j) Micro-CT coronal, sagittal, three-dimensional reconstruction, and new bone imaging, where the scale bar is 5 mm in the Micro-CT coronal and sagittal images, and 2 mm in the three-dimensional reconstruction and new bone imaging images. This indicates that compared to the titanium group, P < 0.05. This indicates that P < 0.01 compared to the titanium group.

[0031] Figure 5 The irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy prepared in Example 2 includes: (a) a schematic diagram of the vapor-assisted alloying-dealloying process and mechanism; (b) a photograph of the sample placed during the vapor-assisted dealloying process; (ce) photographs of commercial titanium alloy implants of different shapes; and (fh) photographs of commercial titanium alloy implants of different shapes after being treated by the vapor-assisted alloying-dealloying process.

[0032] Figure 6 The irregularly shaped titanium alloy screw with enhanced bone regeneration and repair efficacy was prepared for Example 2; wherein, (a) is a photograph of the original titanium alloy screw, and (b) is a photograph of the treated titanium alloy screw.

[0033] Figure 7 The role of the irregular porous titanium implant with enhanced bone regeneration and repair efficacy prepared in Example 2 in the regeneration and repair of rabbit femoral condyles; wherein, (a) flowchart of the evaluation of the osteogenic effect of the porous titanium implant in rabbits, (b) schematic diagram of X, Y and Z axes of microCT reconstructed images, (ce) quantitative analysis of bone mineral density (BMD), (d) bone volume fraction (BV / TV%) and (e) trabecular spacing (Tb.Sp), and (f) microCT cross-section, coronal plane, new bone & screw and new bone images.

[0034] Figure 8 The diagram shows a porous titanium implant for human use; (a) a titanium mesh cage, (b) pedicle screw fixation and (c) a physical image of the porous titanium implant used in laminectomy; (d) the morphology of the implant used in laminectomy inserted into the green area in the diagram; (e) an enlarged morphology of the red area in (d); and (f, g) the morphology of the porous structure in the yellow and blue areas in (e), respectively. Detailed Implementation

[0035] It should be noted that the following detailed description is illustrative and intended to provide further explanation of the invention. Unless otherwise specified, all technical and scientific terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0036] The present invention will be further described below with reference to the embodiments.

[0037] Example 1 Commercial titanium rods (CP-Ti, grade 2) were cut into Φ10 mm × 2 mm (Ti disks) and Φ2 mm × 5 mm (Ti rods) using a diamond wire cutter. The titanium disks were used as the substrate for in vivo subcutaneous ectopic osteogenic experiments, and the titanium rods were used for in vivo femoral implantation experiments. All samples were sequentially polished with P400, P800, and P1200 silicon carbide sandpaper, followed by ultrasonic cleaning in acetone, alcohol, and deionized water, respectively. The cleaned titanium disks and rods were annealed in a tube furnace at 700°C for 3 hours to relieve stress. Subsequently, the annealed titanium disks or rods were sealed together with zinc particles in a quartz tube (within a low vacuum of 1–10 Pa) and subjected to vapor phase alloying (VPA) at 700°C for 6 hours in a muffle furnace. Finally, the alloyed titanium disk or titanium rod precursor was placed in a quartz tube and placed in a tube furnace at 650°C. In the tube furnace, titanium foil was placed at both ends of the quartz tube to remove trace amounts of oxygen, nitrogen and other gases remaining in the vacuum environment. An argon-hydrogen mixture containing 7 vol.% hydrogen was used as a standard gas to further ensure that the sample was not oxidized. The sample was held at 100 Pa for 2 hours for vapor phase dealloying (VPD) treatment to obtain a porous titanium disk (p-Ti disk) or a porous titanium rod (p-Ti rod).

[0038] Experimental Example 1 1. Characterization of porous titanium alloys The actual photographs and microstructures of the p-Ti disk prepared in Example 1 are shown below. Figure 1 As shown in Figure 2, the actual photograph reveals a distinct crack-like texture. Unlike existing technologies that primarily feature single-pore structures, the porous titanium alloy prepared in this application exhibits a hierarchical porous structure under scanning electron microscopy (SEM). At low magnification, it displays elongated ravines (100 μm ravines) and larger pores (50 μm cavity). Further magnification of the morphology within the ravines reveals coral-like ligaments and nest-like channels (1 μm). Energy dispersive spectroscopy (EDS) results show the presence of a small amount of Zn (1.6 at.%). Figure 1 (e) Not removed during the vapor-phase dealloying (VPD) process. Figure 1 Inductively coupled plasma mass spectrometry (ICP-MS) results showed that residual Zn was slowly released in PBS solution, promoting osteoblast growth. The corrosion resistance of the porous material was tested using a Tafel assay. Figure 1 (medium g), compared with commercial Ti (-0.177 V vs. saturated calomel electrode, 3.932 × 10⁻⁶ V), and commercial Ti (-0.177 V vs. saturated calomel electrode, 3.932 × 10⁻⁶ V). -6 A) Compared to a saturated calomel electrode, the p-Ti disk has a more positive corrosion potential (-0.142 V vs. saturated calomel electrode) but a slightly higher corrosion current (5.018 × 10⁻⁶ V). -6A) indicates that p-Ti disks have better corrosion resistance, but the continuous release of residual zinc inside the porous structure increases the self-corrosion current. Figure 1 (f). X-ray diffraction results show that the material is dominated by α-phase Ti with a small amount of β-phase Ti, which may be due to the phase transformation caused by the Zn extraction process. Figure 1 (h).

[0039] 2. Effects of porous titanium on osteogenic differentiation of rat BMMSCs The effect of the porous titanium (p-Ti) scaffold prepared in Example 1 on the osteogenic differentiation capacity of bone marrow mesenchymal stem cells (BMMSCs) was evaluated using RT-PCR. Rat BMMSCs (4 × 10⁻⁶) were used in the study. 4 After culturing the scaffold surface in 24-well plates for 3 days, the expression levels of osteogenic-related genes, including alkaline phosphatase (ALP), osteocalcin (OCN), Runt-associated transcription factor 2 (RUNX2), and type I collagen (COL1), were quantitatively analyzed by reverse transcription polymerase chain reaction (RT-PCR). Compared with the titanium group (commercial titanium without porous treatment), the porous titanium scaffold significantly increased the mRNA expression levels of ALP, OCN, RUNX2, and COL1. Figure 2 (Ad), with the expression level of the OCN gene increasing nearly fourfold.

[0040] Immunofluorescence staining was used to detect ALP protein expression, and the results showed that ALP in the porous titanium group ( Figure 2 The expression levels of e and f in the middle group were significantly higher than those in the titanium group.

[0041] 3. Porous titanium regulates macrophage immune aging and inhibits the secretion of inflammatory factors. Macrophages were further seeded onto the surface of porous titanium modules and titanium implants in six-well plates and cultured for 2 days. Figure 3 As shown in the figure below, compared with other groups, the expression of mannose receptor (CD206) in macrophages was significantly increased in the porous titanium group (P<0.05), while the expression of inducible nitric oxide synthase (iNOS) showed no statistically significant difference. Meanwhile, the expression of arginase 1 (ARG1) and bone morphogenetic protein 2 (BMP2), which are related to M2 polarization and osteogenic processes, was significantly increased in the porous titanium group (P<0.01), an effect attributed to its porous structure. Previous studies have found that ARG1... +Macrophage subsets are activated in young tissues but suppressed in senescent tissues; these subsets are key regulators of aging-related regenerative immune responses. Macrophage senescence leads to functional impairment and may trigger the accumulation of abnormal proteins (pathological markers of various diseases). M2 macrophages participate in immune regulation by secreting anti-inflammatory factors such as IL-4 and TGFβ, and are highly expressed in young individuals. Immunofluorescence staining showed that the density of CD206+ cells in the porous titanium group was significantly higher than that in the titanium group (…). Figure 3 The study confirmed its significant tendency to induce M2 polarization. Enzyme-linked immunosorbent assay (ELISA) showed that the porous titanium group promoted the secretion of the M2-related cytokine IL10 (…). Figure 3 f, P<0.05), while inhibiting the release of pro-inflammatory factor IL6 (P<0.05). Figure 3 (g, P<0.01). The above data indicate that porous titanium promotes bone regeneration by regulating the M2 immunosenescence phenotype (enhanced IL10 secretion).

[0042] The porous titanium prepared in Example 1 possesses a high specific surface area and a three-dimensional porous structure, comprising micropores of approximately 1 μm, cavities of approximately 50 μm, and ravines approximately 100 μm wide. This structure effectively promotes ARG1. + Macrophage generation and M2 polarization. Experiments showed that porous titanium significantly increased the expression of M2 polarization-related proteins and induced macrophages to transform into an anti-aging phenotype, while significantly reducing the expression of aging markers p16 and p21 in these immunomodulatory cells. Figure 3 (h in the middle, i in the middle). This phenotypic regulation may play a key role in promoting tissue repair and regeneration.

[0043] The above results indicate that porous titanium can effectively promote osteogenic differentiation, reverse macrophage senescence, and has great potential to promote the regeneration of senescent bone in vitro.

[0044] 4. Porous titanium implants promote osseointegration in bone defect models To evaluate the in vivo osteogenic effects of titanium and porous titanium implants, cylindrical implants (titanium rods and porous titanium rods) were implanted into the distal femoral metaphysis of rats with bone defects. The entire surgical procedure adhered to aseptic techniques and the ethical standards of Qilu Hospital of Shandong University. The specific procedures included femoral exposure, implantation site localization, drilling, and implantation. Calcein Green was administered intraperitoneally 4 weeks postoperatively, Alizarin Red was administered at 6 weeks, and a micro-CT scan was performed at 8 weeks.

[0045] Methodology: The rat femoral defect model construction and in vivo experimental protocol were approved by the Animal Nursing Committee of Qilu Hospital, Shandong University (Approval No.: DWLL-2021-034), and all procedures followed the guidelines of the hospital's Ethics Committee. Rats were anesthetized under aseptic conditions, and a bone defect model was constructed in the distal femur. A cylindrical implant (Φ2 mm × 5 mm) was then implanted into the defect site to observe in vivo bone regeneration and repair. At weeks 4 and 6 post-surgery, early and late-stage new bone were labeled with Calcein Green and Alizarin Red, respectively, via intraperitoneal injection. At week 8, rats were euthanized, and femoral tissue was harvested. Changes in femoral length after implantation were assessed by measuring the proximal-distal femoral distance.

[0046] Results: Femoral length measurements 8 weeks after implantation showed no significant difference between the titanium group and the porous titanium group. Figure 4 (a) and (c) in section 4 confirmed that porous titanium implantation does not affect bone development. Laser confocal imaging of bone tissue sections showed that in dual-labeling detection of calcein (early osteogenic marker) and alizarin red (late osteogenic marker), the porous titanium group had a significant advantage in both early and late osteogenic stages. Figure 3 (b in group B, d in group 4) Further comparison of the pathological findings of rat organs in each experimental group confirmed that the physiological state of solid organs was not affected by the implant. Figure 4 (e), which verified its biocompatibility in vivo.

[0047] Micro-CT three-dimensional reconstruction confirmed the formation of a dense new bone layer around the porous titanium implant: bone volume fraction (BV / TV) increased by 50%, trabecular bone number (Tb.N) and thickness (Tb.Th) significantly increased, and trabecular bone separation (Tb.Sp) decreased. Figure 4 In the middle section, a three-dimensional perspective more intuitively displays the uniform and dense new bone structure surrounding the porous titanium assembly. Figure 4 (j).

[0048] These results confirm that porous titanium implants can effectively increase early and late-stage osteogenic capacity while ensuring normal bone development, providing a breakthrough solution for the clinical treatment of bone defects.

[0049] Example 2 After cleaning and annealing, irregularly sized titanium alloy (TC4(Ti-6Al-4V)) workpieces were placed together with zinc particles in a low vacuum (1~100 Pa) and high temperature (700 ℃) environment for 6 hours. The zinc vaporized and adsorbed onto the workpiece surface, diffusing to form a titanium-zinc intermetallic compound. The alloy layer thickness gradually increased with prolonged holding time. During the subsequent dealloying process, to eliminate the influence of airtightness and gases such as oxygen, sacrificial titanium foil was placed at the opening of a quartz tube, and an auxiliary gas (high-purity argon or an argon-hydrogen mixture containing 7 vol.% hydrogen) was introduced. At the start of dealloying, zinc atoms in the alloy layer were released due to the vacuum (100 Pa) and high temperature (650 ℃) conditions, creating voids where zinc atoms had previously occupied. The remaining titanium alloy atoms rearranged to form a ligamentous structure. After holding for 2 hours, a porous material was formed. Figure 5 In sections a and b, three different shapes of commercially available titanium implants were selected, such as... Figure 5 The structure of CE after dealloying is as follows: Figure 5 In the middle fh, after dealloying, the geometry of the implant did not change significantly, but the surface roughness showed a significant change.

[0050] Meanwhile, to verify the application performance of porous irregular-shaped parts prepared by this method, commercial animal screws (φ2.7 mm × 20 mm) were used in the study of porous structure preparation by vapor phase assisted alloying dealloying process. The original and processed titanium alloy screws were compared. Figure 6 As shown in a and b.

[0051] Experimental Example 2 Methodology: Construction and in vivo experiments of a rabbit femoral defect model. All animal procedures were approved by the Animal Experiment Ethics Committee of Qilu Hospital, Shandong University (Approval No.: DWLL-202400084). Skeletal-mature New Zealand white rabbits (weighing 3.0 ± 0.5 kg) were randomly assigned to the titanium screw group and the porous titanium screw group. After general anesthesia, all experimental rabbits underwent surgery in their left hind limb to establish a standardized intra-articular fracture model by an experienced orthopedic surgeon. After aseptic preparation of the surgical area, a 5 cm incision was made along the lateral side of the patella to expose the femoral condyle. Orthogonal osteotomies were performed at the apex of the superior lateral pole and inferior medial pole of the patella using a 1 mm oscillating saw. After temporary reduction of the fracture, a 2.0 mm bicortical bone tunnel was drilled in the medial femoral condyle, and screws were then implanted with calibrated inter-fracture pressure. The wound was closed in layers with non-absorbable sutures. For 7 days postoperatively, the animals were housed in confined cages, given daily subcutaneous antibiotic prophylaxis, and their hydration and nutritional status were monitored. Complications such as infection, implant failure, or mobility impairment were assessed.

[0052] Titanium screws or porous titanium screws were implanted in rabbits to evaluate the bone regeneration and repair effects of porous titanium in rabbit models and to prepare for preclinical application. Figure 7(a) Micro-CT analysis 8 weeks after implantation showed that, compared with the traditional titanium control group, the porous titanium group exhibited significantly enhanced bone regeneration at the femoral defect site, specifically manifested as increased bone mineral density (BMD), bone volume fraction (BV / TV), and decreased trabecular spacing (Tb.Sp). Figure 7 (middle be). A three-dimensional view intuitively displays the uniform and dense new bone structure around the porous titanium assembly. Figure 7 (f) The above results clearly confirm that porous titanium significantly promotes osteogenic formation in vivo. These findings demonstrate the ability of porous titanium materials to promote bone regeneration in rabbits, providing mechanistic evidence for its immunomodulatory role in the bone regeneration and repair microenvironment, and supporting its potential for translational application in clinical bone repair treatment.

[0053] For subsequent clinical validation, commercially available implants for human use are being further studied, such as... Figure 8 In the treatment of different spinal regions, implants of various shapes are used. These include titanium mesh cages, pedicle screws, and porous titanium implants used in laminectomy. The morphology of the porous structure on the implant surface is characterized, such as… Figure 8 As can be seen from d, due to geometric constraints and the vapor-phase dealloying mechanism, its surface morphology exhibits a multi-sized porous structure, with obvious groove-like and pore-like structures. Figure 8 High-magnification morphological observation of the yellow and blue rectangular regions in 8e revealed the presence of secondary ligament-pore structures within porous structures of different sizes, which is beneficial for osteoblast growth. Figure 8 f and g).

[0054] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A shaped titanium alloy with enhanced bone regeneration and repair efficacy, characterized in that, The irregular titanium alloy comprises an irregular titanium alloy matrix and a porous structure attached to the irregular titanium alloy matrix; the porous structure includes elongated grooves and pores; the morphology within the grooves shows coral-like ligaments and nest-like channel structures.

2. The irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy according to claim 1, characterized in that, The elongated grooves are 100-150 μm wide, the pores are 30-50 μm in size, and the hollow channels are 0.5-2 μm in size.

3. The irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy according to claim 1, characterized in that, The irregular titanium alloy includes titanium mesh cages, pedicle screws, and porous titanium implants used in laminectomy.

4. A method for preparing an irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy, characterized in that, Includes the following steps: S1, Vapor phase alloying treatment of irregularly shaped titanium alloys: The irregularly shaped titanium alloy workpiece and the sacrificial metal are placed together in a vacuum of 1~100 Pa and a temperature of 600~800℃ for 1~15 hours to carry out vapor phase alloying to obtain the precursor. S2, Vapor phase dealloying treatment: Place the irregularly shaped titanium alloy precursor after the vapor phase alloying treatment in step S1 in a container and incubate at 550~750℃ for 1×10⁻⁶ days. -2 Vapor phase dealloying is performed by holding the material at ~100 Pa for 1~2 hours.

5. The method for preparing the irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy as described in claim 3, characterized in that, In step S1, the sacrificial metal is zinc particles.

6. The method for preparing the irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy as described in claim 3, characterized in that, In steps S1 and S2, the container is a quartz tube.

7. The method for preparing the irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy as described in claim 3, characterized in that, In step S1, vapor phase alloying is performed in a muffle furnace; in step S2, vapor phase dealloying is performed in a tube furnace.

8. The method for preparing the irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy according to claim 3, characterized in that, In step S2, titanium foil is placed on both sides of the titanium alloy in the container to ensure airtightness and to eliminate the influence of gases such as oxygen and nitrogen.

9. The method for preparing the irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy according to claim 3, characterized in that, In step S2, an auxiliary gas is introduced into the quartz tube; the auxiliary gas is argon or an argon-hydrogen mixture.

10. The application of the irregularly shaped titanium alloy with enhanced bone regeneration and repair efficacy as described in any one of claims 1 to 2 in the preparation of bone implants.

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