Design method of multifunctional modular bone defect implant stent

Abstract

The invention discloses a design method of a multifunctional modular bone defect implant scaffold, and belongs to the technical field of orthopedic implant design, the method comprises the following steps: S10, endowing a structural implicit function model with biomorphological parameters of a bone scaffold to obtain a single-pore bone scaffold model; s20, performing parametric design on the single-pore bone scaffold model to obtain a scaffold structure with a human cancellous bone imitating structure; s30, designing a single-pore-channel scaffold structure so as to evolve the scaffold structure from a single pore channel to a double-pore-channel and three-pore-channel structure, and obtaining a structure with mutually independent pore channels and enough pore channels; and S40, endowing the three-duct stent with compact outer layers with different wall thicknesses to obtain an implant stent model of the outer duct of the three-duct stent. According to the invention, the bone scaffold is subjected to structural design and functional modular partition design, the functions of immunization, antibiosis, tumor recurrence prevention, photo-thermal treatment and the like are subjected to personalized combination, and the loading capacity is regulated and controlled.

Description

Technical Field

[0001] The invention belongs to the technical field of orthopedic implant design and relates to a design method of a multifunctional modular bone defect implant bracket. Background Art

[0002] Since bone defects caused by tumors, trauma, infection, etc. are common clinical diseases, the common surgical treatment method is to place orthopedic implants in the defect area. It is reported that the global orthopedic implant market size will reach approximately US$48.6 billion in 2024. Usually, bone defect scaffolds need to have basic functions such as mechanical bearing, cell adhesion and bone tissue regeneration; at the same time, bone defect scaffolds should also have the following different functions under different application conditions: immunity, antibacterial, prevention of tumor recurrence and photothermal therapy.

[0003] like Figure 1 As shown in (a), Shan et al. prepared a strontium-doped β-TCP bioceramic scaffold (Sr-TCP) with a TPMS structure by using a photocurable 3D printing technology (DLP technology). When the scaffold porosity was 80%, the mechanical strength was as high as 1.44 MPa. Figure 1 (b) The results of alkaline phosphatase staining and PCR experiments showed that it has the effect of promoting bone regeneration. Figure 1 (c) Professor Li Xiaokang and his colleagues from the Tangdu Hospital of the Fourth Military Medical University successfully prepared a barium titanate / iron coating with photothermal efficacy on a 3D-printed porous titanium alloy stent by hydrothermal growth. After the photothermal effect killed the tumor, the iron ions were continuously released. Figure 1 (d) It shows good bone tissue regeneration performance. However, the single function of the scaffold cannot meet the treatment plan for complications caused by bone defects in patients.

[0004] In addition, existing multifunctional stents often load immune drugs, antibacterial drugs, chemotherapy drugs, and photothermal materials into the stents through immersion, surface modification, hydrogel composite, and microsphere composite methods. The drug loading capacity is limited, the sustained release effect is poor, and the drug action cycle is short, making it difficult to maintain and exert bone tissue repair, immunity, antibacterial, controlled drug release, and photothermal effects in a long-term and effective manner. Summary of the invention

[0005] In order to solve the above problems, the present invention adopts the following technical solutions:

[0006] A design method for a multifunctional modular bone defect implant scaffold comprises the following steps:

[0007] S10, assigning the biomorphic parameters of the bone scaffold to the structural implicit function model to obtain a single-channel bone scaffold model;

[0008] S20, performing parameterized design on the single-channel bone scaffold model to obtain a scaffold structure that mimics the structure of human cancellous bone;

[0009] S30, designing a single-pore stent structure to evolve the stent structure from a single-pore structure to a double-pore structure and a triple-pore structure, so as to obtain a structure in which the pores are independent of each other and the pores have enough space for loading cell adhesion, loading drugs and photothermal materials;

[0010] S40, giving the three-channel stent a dense outer layer with different wall thicknesses to personalize the mechanical strength of the patient's bone tissue, thereby obtaining an implant stent model of the outer channel of the three-channel stent.

[0011] Furthermore, the dense outer layer of the three-channel stent with different wall thicknesses is used to personalize the mechanical strength of the patient's bone tissue, specifically including:

[0012] S41, transforming a single three-periodic minimal surface structure into a double-channel minimal surface with a middle-through structure by adjusting parameters;

[0013] S42. In two double-channel three-period minimal surface structure stents with the same period, one of them is translated in the horizontal direction by half a period to obtain a three-channel stent, which is used to load immune, antibacterial, chemotherapy drugs or photothermal materials respectively;

[0014] S43. By Boolean operation, a dense outer layer with different wall thicknesses is added to the bone scaffold model for mechanical bearing, thereby obtaining an implant scaffold model with three-channel outer channels.

[0015] Further, the structural implicit function model is a Diamond model, a Gyroid model or a Schwarz p model;

[0016] Wherein, the Diamond model is:

[0017]

[0018] The Gyroid model is:

[0019]

[0020] The Schwarzp type model is:

[0021]

[0022] In the formula, a is the period of the minimal surface structure; x, y, z are spatial independent variables; C is the offset, which determines the porosity of a single channel; For the control function.

[0023] Further, in step S20, the period a of the minimal surface structure ranges from 1.5 to 5.

[0024] Further, in step S30, the porosity of the bone scaffold model is adjusted when the minimal surface structure is a single-channel structure by designing an offset, so as to achieve the subsequent three-channel structure design in which the channels are independent of each other and there is enough space to load drugs and photothermal materials;

[0025] After the minimum surface is adjusted, the offset C is fitted with the porosity fitting curve, and the porosity fitting curve is:

[0026] When the structural implicit function model is the Diamond model: P=42C+49;

[0027] When the structural implicit function model is the Gyroid model: P=33C+45;

[0028] When the structural implicit function model is the Schwarzp type: P = 28C + 47.5;

[0029] Where P is the porosity and C is the offset.

[0030] Furthermore, the porosity of the single-channel structured stent can be adjusted in the range of 20% to 80%.

[0031] Further, in step S41, the parameter t is adjusted to transform the single three-periodic minimal surface structure into a double-channel minimal surface with a central through structure. Different t values ​​correspond to the porosity P1 of the inner channel of the double-channel scaffold;

[0032] Wherein, when the structural implicit function model is the Diamond model: P1=42.2t+49.5;

[0033] When the structural implicit function model is the Gyroid model: P1=33.2t+50.3;

[0034] When the structural implicit function model is the Schwarzp type: P1=30t+51.

[0035] Furthermore, the value range of t is -0.9 to -0.2, and the porosity of the inner channel is in the range of 10% to 60%.

[0036] Further, in step S42, among two double-channel three-periodic minimal surface structure brackets with the same period, one of them is translated half a period in the horizontal direction along the x-axis or the y-axis.

[0037] Furthermore, in step S43, in order to make the mechanical strength and Young's modulus of the implant scaffold match those of human bones, the ratio of the dense outer layer thickness to the scaffold radius is in the range of 0 to 0.4; the outer channels of the three-channel scaffold are used for cell adhesion and bone tissue growth, the cell adhesion pore size is 300 to 600 μm, and the porosity of the outer channels of the three-channel scaffold is in the range of 5% to 40%.

[0038] Beneficial effects:

[0039] The present invention provides a design method for a multifunctional modular bone defect implant scaffold. Based on the basic functions of mechanical bearing, cell adhesion and bone tissue repair required for the bone defect scaffold, structural design and functional modular zoning design are performed. According to the treatment plan for the patient's disease, personalized combinations of functions such as immunity, antibacterial, prevention of tumor recurrence and photothermal therapy can be performed, and the loading amount can be regulated.

[0040] In addition, the present invention performs structural and functional modular partitioning design on the TPMS with a bionic structure, and based on ZTA / Ca2MgSi2O7 composite ceramics, uses light-curing 3D printing technology to prepare a multifunctional, modular bone defect scaffold to achieve functions such as mechanical bearing, cell adhesion and osteogenesis, while taking into account customized options for immunity, antibacterial, prevention of tumor recurrence, and photothermal therapy functions. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 (a) is a model display of 3D printed Sr-TCP ceramic scaffold with TPMS structure, (b) is the mechanical properties and biological performance evaluation of promoting bone regeneration found through alkaline phosphatase staining and PCR experiments; (c) is the preparation process of porous titanium alloy scaffold with barium titanate / iron coating; (d) is a display of good bone tissue regeneration performance;

[0042] Figure 2 is the porosity and offset fitting curve;

[0043] Figure 3 It is a schematic diagram of the double-channel bracket structure;

[0044] Figure 4 is the linear relationship between the porosity of the double-channel and the parameter t;

[0045] Figure 5 It is a schematic diagram of the three-channel bracket structure;

[0046] Figure 6 Schematic diagram of adding a dense outer wall to a double-channel support structure and a three-channel support structure;

[0047] Figure 7The photothermal properties of the scaffold: (a) is a real-time infrared thermal imaging image; (b) is a temperature change curve; (c) is a thermal recovery curve of 0.25 mm thick artificial bone and (d) is the photothermal conversion efficiency;

[0048] Figure 8 is the ZOL drug release rate of the stent at different pH values. DETAILED DESCRIPTION

[0049] Example 1

[0050] A design method for a multifunctional modular bone defect implant scaffold, comprising:

[0051] S10, assigning the biomorphic parameters of the bone scaffold to the structural implicit function model to obtain a single-channel bone scaffold model;

[0052] S20, performing parameterized design on the single-channel bone scaffold model to obtain a scaffold structure that mimics the structure of human cancellous bone;

[0053] S30, designing a single-pore stent structure to evolve the stent structure from a single-pore structure to a double-pore structure and a triple-pore structure, so as to obtain a structure in which the pores are independent of each other and the pores have enough space for loading cell adhesion, loading drugs and photothermal materials;

[0054] S40, giving the three-channel stent a dense outer layer with different wall thicknesses to personalize the mechanical strength of the patient's bone tissue, thereby obtaining an implant stent model of the outer channel of the three-channel stent.

[0055] In this embodiment, in step S40, the three-channel stent is given a dense outer layer with different wall thicknesses to personalize the mechanical strength of the patient's bone tissue, specifically including:

[0056] S41, transforming a single three-periodic minimal surface structure into a double-channel minimal surface with a middle-through structure by adjusting parameters;

[0057] S42. In two double-channel three-period minimal surface structure stents with the same period, one of them is translated in the horizontal direction by half a period to obtain a three-channel stent, which is used to load immune, antibacterial, chemotherapy drugs or photothermal materials respectively;

[0058] S43. By Boolean operation, a dense outer layer with different wall thicknesses is added to the bone scaffold model for mechanical bearing, thereby obtaining an implant scaffold model with three-channel outer channels.

[0059] In this embodiment, the structural implicit function model is a Diamond model, a Gyroid model or a Schwarz p model.

[0060] in,

[0061] The Diamond model is:

[0062]

[0063] The Gyroid model is:

[0064]

[0065] The Schwarz p-type model is:

[0066]

[0067] In the formula, a is the period of the minimal surface structure; x, y, z are spatial independent variables; C is the offset, which determines the porosity of a single channel; For the control function.

[0068] Wherein, in step S20, the period a of the minimal surface structure ranges from 1.5 to 5, and the value a is designed to adjust the period of the minimal surface so that the bracket can better simulate the structure of the human cortical bone bracket.

[0069] In step S30, after the minimum surface is adjusted, the offset C is fitted with the porosity fitting curve, and the porosity fitting curve is:

[0070] When the structural implicit function model is a Diamond model: P = 42C + 49;

[0071] When the structural implicit function model is a Gyroid model: P = 33C + 45;

[0072] When the structural implicit function model is Schwarzp type: P = 28C + 47.5;

[0073] Where P is the porosity and C is the offset.

[0074] In this embodiment, the offset C is designed to adjust the porosity of the support when the minimal curved surface structure is a single-channel structure. Figure 2 Fitting curves of post-segment offset C and porosity for different minimal surfaces were developed to ensure that the subsequent three-channel structure design has independent channels and sufficient space for loading drugs and photothermal materials. The porosity adjustment range of the single-channel structure stent is 20% to 80%.

[0075] In this embodiment, in step S41, the parameter t is adjusted to transform the single three-periodic minimal surface structure into a double-channel minimal surface with a central through structure. The schematic diagram is shown in Figure 3. Different t values ​​correspond to the porosity P1 of the double-channel stent. Figure 4 ;

[0076] Among them, when the structural implicit function model is a Diamond model: P1 = 42.2t + 49.5;

[0077] When the structural implicit function model is a Gyroid model: P1 = 33.2t + 50.3;

[0078] When the structural implicit function model is of Schwarzp type: P1=30t+51.

[0079] In order to successfully prepare the bone scaffold and ensure that the wall thickness of the bone scaffold is not too thin, in this embodiment, the value range of t is -0.9 to -0.2, and the porosity range of the inner channel is 10% to 60%.

[0080] In step S42, among two double-channel three-periodic minimal surface structure brackets with the same period, one of them is horizontally translated along the x-axis or y-axis by half a period to obtain a three-channel bracket structure with independent channels, as shown in the schematic diagram. Figure 5 shown.

[0081] In step S43, in order to make the mechanical strength and Young's modulus of the implant scaffold match those of human bones, a dense outer layer with different wall thicknesses is added to the scaffold through Boolean operations to simulate different human cortical bones, and the ratio of the dense outer layer thickness to the scaffold radius ranges from 0 to 0.4; the outer channels of the three-channel scaffold are used for cell adhesion and bone tissue growth, and the most suitable pore size for cell adhesion is 300 to 600 μm, and the porosity of the outer channels of the three-channel scaffold ranges from 5% to 40%.

[0082] The inner channels of the three-channel stent provided in this embodiment can be used to load different antibacterial, immune and chemotherapy drugs, etc. The above drugs can be mixed with degradable organic matter as required, and the mixed solution can be poured into the inner channels of the stent with a syringe to achieve controlled release of the drugs.

[0083] For materials that do not need to be released, such as photothermal materials, the material can be injected into the inner channel, and then ZTA / Ca2MgSi2O7 ceramic slurry can be applied to the upper and lower surfaces and cured by ultraviolet light to obtain a completely closed independent inner hole.

[0084] The multifunctional bionic bone scaffold designed by the design method of the multifunctional modular bone defect implant scaffold provided in this embodiment has independent channels inside for functional modularization, and the internal multiple channels are used to simulate human cancellous bone; a dense outer wall is added on the outside to act as cortical bone, thereby improving the mechanical strength and Young's modulus of the implant scaffold.

[0085] The outer pores of the internal porous structure provided in this embodiment are used for cell adhesion and bone tissue ingrowth, and the porosity ranges from 10% to 30%.

[0086] The inner channel is used to load immune, antibacterial, anti-tumor drugs and photothermal materials, etc., and can realize functional combinations such as immune-antibacterial, immune-antitumor, immune-photothermal therapy, antibacterial-antitumor, antibacterial-photothermal therapy, and antitumor-photothermal therapy. The porosity of the inner channel ranges from 10% to 60%.

[0087] By adjusting the porosity of the inner channel and the loading drug concentration, the drug release rate can be adjusted from 30% to 80% in 30 days.

[0088] The inner channel is loaded with photothermal materials, and the temperature can reach 45℃~80℃ under near-infrared light irradiation, which can kill surrounding bone tumor cells. It has good thermal stability and the photothermal conversion efficiency can reach 15%~40%.

[0089] According to the patient's needs, the ratio of the dense outer layer thickness to the stent radius is in the range of 0 to 0.4, the mechanical strength of the stent can be adjusted to 5 to 400 MPa, and the Young's modulus is 0.2 to 4 GPa.

[0090] Example 2

[0091] This embodiment is based on the embodiment 1 and takes the Diamond model as an example for further explanation.

[0092] In this embodiment, the three-channel D-shaped minimal surface structure has three internal channels that simulate human cancellous bone, of which the outer channel is used for cell adhesion and bone tissue ingrowth; the other two channels are loaded with chemotherapy drugs (ZOL) and photothermal materials (MXene), etc., to achieve drug and photothermal therapy to prevent tumor recurrence. The outer dense outer layer simulates human cortical bone to improve the mechanical strength and Young's modulus of the scaffold.

[0093] The specific design steps are as follows:

[0094] Diamond structure implicit functions are as follows:

[0095]

[0096] First, design a three-channel bracket according to Figure 2 The fitting curve P=42C+49 is used to establish a single-channel support structure with porosities of 55% and 60%, model radius r=5mm, height h=5mm, and a=1.5 by changing the offset C.

[0097] Subsequently, according to Figure 4 Fitting the porosity and parameters of the double-channel inner pores Linear relationship: P1=42.2t+49.5, giving the single-channel scaffolds with porosity of 55% and 60% a t value of -0.478, double-channel scaffolds with inner channel porosity of 25% and 20% can be obtained respectively.

[0098] Finally, one of the double-channel structure brackets is translated along the horizontal x-axis or y-axis by half of the period to obtain a three-channel bracket structure with independent channels, such as Figure 5 As shown, at this time, the porosity of the two sets of independent inner channels of the stent is 20% and 25% respectively, the porosity of the outer channel is 15%, and the total porosity is 60% (numbered 60-20-25-15). Through Boolean operation, 0mm, 0.25mm, and 0.5mm dense outer walls are added to the three-channel stent to bear the mechanical strength, as shown in FIG. Figure 6 shown.

[0099] The designed bone scaffold structure was meshed using HyperMesh software and imported into Abaqus software for compressive strength mechanical simulation. The results are shown in the following table:

[0100]

[0101] The results show that the mechanical strength and Young's modulus of the stent can be changed by changing the stent wall thickness to personalize the strength requirements of different patients.

[0102] The porosity of the scaffold is 25% and the photothermal material is loaded into the pores. 2 When exposed to near-infrared light, the temperature of the stent increases and the surrounding tumor cells are killed. Figure 7 As shown, it is known that tumor cell ablation is usually performed at a temperature less than 50°C. From the results, it can be seen that the stent has excellent photothermal stability and photothermal conversion efficiency, which can quickly kill tumor cells and reduce damage to normal tissues.

[0103] When the porosity of the scaffold is 20%, the ZOL anti-tumor drug is loaded into the scaffold. Under different pH buffer conditions, the drug release rate of the scaffold is as follows: Figure 8 As shown, it can be seen from the results that the stent has the ability to release drugs continuously and stably.

[0104] The above description is only a preferred embodiment of the present invention and does not limit the technical scope of the present invention. Therefore, any slight modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A design method for a multifunctional modular bone defect implant scaffold, characterized in that: The following steps are involved: S10, assigning the biomorphic parameters of the bone scaffold to the structural implicit function model to obtain a single-channel bone scaffold model; S20, performing parameterized design on the single-channel bone scaffold model to obtain a scaffold structure that mimics the structure of human cancellous bone; S30, designing a single-pore stent structure to evolve the stent structure from a single-pore structure to a double-pore structure and a triple-pore structure, so as to obtain a structure in which the pores are independent of each other and the pores have enough space for loading cell adhesion, loading drugs and photothermal materials; S40, giving the three-channel stent a dense outer layer with different wall thicknesses to personalize and match the mechanical strength of the patient's bone tissue, thereby obtaining an implant stent model of the outer channel of the three-channel stent.

2. The design method of the multifunctional modular bone defect implant scaffold according to claim 1, characterized in that: The dense outer layer of the three-channel stent with different wall thicknesses is used to individually match the mechanical strength of the patient's bone tissue, specifically including: S41, transforming a single three-periodic minimal surface structure into a dual-channel minimal surface with a middle-through structure by adjusting parameters; S42. In two double-channel three-period minimal surface structure stents with the same period, one of them is translated in the horizontal direction by half a period to obtain a three-channel stent, which is used to load immune, antibacterial, chemotherapy drugs or photothermal materials respectively; S43. By Boolean operation, a dense outer layer with different wall thicknesses is added to the bone scaffold model for mechanical bearing, thereby obtaining an implant scaffold model with three-channel outer channels.

3. The design method of the multifunctional modular bone defect implant scaffold according to claim 2, characterized in that: The structural implicit function model is a Diamond model, a Gyroid model or a Schwarz p model; Wherein, the Diamond model is: The Gyroid model is: The Schwarzp type model is: In the formula, a is the period of the minimal surface structure; x, y, z are spatial independent variables; C is the offset, which determines the porosity of a single channel; For the control function.

4. The design method of the multifunctional modular bone defect implant scaffold according to claim 3, characterized in that: In step S20, the period a of the minimal surface structure ranges from 1.5 to 5.

5. The design method of the multifunctional modular bone defect implant scaffold according to claim 3, characterized in that: In step S30, the porosity of the bone scaffold model is adjusted by designing an offset when the minimal curved surface structure is a single-channel structure, so as to achieve the subsequent three-channel structure design in which the channels are independent of each other and there is enough space to load drugs and photothermal materials; After the minimum surface is adjusted, the offset C is fitted with the porosity fitting curve, and the porosity fitting curve is: When the structural implicit function model is the Diamond model: P=42C+49; When the structural implicit function model is the Gyroid model: P=33C+45; When the structural implicit function model is the Schwarzp type: P = 28C + 47.5; Where P is the porosity and C is the offset.

6. The design method of the multifunctional modular bone defect implant scaffold according to claim 5, characterized in that: The porosity adjustment range of the single-channel structure bracket is 20% to 80%.

7. The design method of the multifunctional modular bone defect implant scaffold according to claim 3, characterized in that: In step S41, the parameter t is adjusted to transform the single three-periodic minimal surface structure into a double-channel minimal surface with a central through structure. Different t values ​​correspond to the porosity P1 of the inner pores of the double-pore scaffold; Wherein, when the structural implicit function model is the Diamond model: P1=42.2t+49.5; When the structural implicit function model is the Gyroid model: P1=33.2t+50.3; When the structural implicit function model is the Schwarzp type: P1=30t+51.

8. The design method of the multifunctional modular bone defect implant scaffold according to claim 7, characterized in that: The value range of t is -0.9 to -0.2, and the porosity of the inner channel ranges from 10% to 60%.

9. The design method of the multifunctional modular bone defect implant scaffold according to claim 3, characterized in that: In step S42, one of the two double-channel three-periodic minimal surface structure brackets with the same period is translated horizontally along the x-axis or y-axis by half a period.

10. The design method of the multifunctional modular bone defect implant scaffold according to claim 3, characterized in that: In step S43, in order to make the mechanical strength and Young's modulus of the implant scaffold match those of human bones, the ratio of the dense outer layer thickness to the scaffold radius is in the range of 0 to 0.4; the outer channels of the three-channel scaffold are used for cell adhesion and bone tissue growth, the cell adhesion pore size is 300 to 600 μm, and the porosity of the outer channels of the three-channel scaffold is in the range of 5% to 40%.

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