Design method of vascularization-promoting mandible implant with controllable functional gradient

Abstract

The invention discloses a design method of a vascularization-promoting mandible implant with a controllable functional gradient. According to the method, mechanical properties and permeability of different types of TPMS structures are analyzed, compared and optimized, and a polymorphic fused TPMS structure is created. Therefore, the implant is based on the TPMS unit, different pore structure types and pore sizes are adopted in the z-axis direction according to different requirements, and functional gradient controllable change is achieved; the implant has the advantages of strong pore connectivity, high permeability and large specific surface area, and is favorable for guiding the growth of blood vessels implanted in the body; stress stimulation can be conducted, so that favorable conditions are provided for adhesion proliferation of bone cells; and meanwhile, the implant is matched with the defective mandible in appearance, so that the natural appearance of the mandible of the patient can be recovered.

Description

Technical Field

[0001] The present invention relates to the technical field of mandibular repair, and in particular to a design and manufacturing method of a mandibular implant with controllable functional gradient and a vascularization-promoting implant. Background Art

[0002] In daily life, the mandible not only gives our face a unique shape, but also plays a vital role in human activities such as chewing and vocalization. External injuries or diseases may cause defects in the mandible and adjacent soft tissues, resulting in serious facial deformities, and also cause functional disorders such as chewing and language to patients, affecting the patient's psychology.

[0003] Bone tissue contains a large number of blood vessel networks, which can provide sufficient oxygen and nutrients to bone cells and promote bone tissue metabolism. Therefore, among the several methods for repairing segmental mandibular defects, autologous bone transplantation is still the main method for mandibular repair due to its advantage of natural blood vessels. However, the transplanted autologous bone cannot match the defective mandibular bone in shape and cannot effectively restore the patient's appearance.

[0004] With the advancement of modern science and technology, more and more metal implants are used in the repair of mandibular defects. Using modern medical imaging technology and digital means, personalized implants that match the shape of defective bone tissue can be designed and manufactured to achieve accurate reconstruction of the shape in the repair of mandibular defects. Titanium alloy is a commonly used bone implant material. It has good biocompatibility with human tissue and does not cause rejection, so it is widely used. However, the stiffness of titanium alloy does not match that of human bone tissue. Its elastic modulus is as high as 110GPa, while the elastic modulus of human cortical bone is only about 12GPa. Titanium alloy implants are prone to side effects such as "stress shielding" after implantation, affecting the success rate of repair. In order to reduce the elastic modulus of metal materials, a porous structure can be used to adjust the porosity. The interconnected pore structure can also meet the spatial requirements of bone cell attachment and growth, promote the growth of bone cells at the implant and the bone end surface, and improve the success rate of bone defect repair. However, a uniform and regular porous structure is usually used at present, without considering that when the implant is subjected to load, different parts exhibit different mechanical properties and functions. Therefore, using a uniform and regular pore structure to adapt to different defect sites is not the best method.

[0005] With the development of additive manufacturing technology, titanium alloys can be used to manufacture more sophisticated and complex porous structures to match bone defects in different parts for repair. Tri-periodic minimal surface (TPMS) is a surface with three-dimensional periodicity in space. Compared with traditional pore structures, the pore structure constructed by TPMS is more continuous inside, and the pore size and porosity are easier to control, which greatly improves the modeling efficiency. The average curvature of the TPMS surface is zero, similar to the zero average curvature of natural trabecular bone, which reduces stress concentration; its large specific surface area is more conducive to cell adhesion, and the controllable pore size can also promote angiogenesis and induce bone tissue regeneration. Therefore, the TPMS unit is suitable as the basic unit of artificial bone scaffolds. Summary of the invention

[0006] For segmental defects of the mandible, taking into account that when the mandibular implant is occluded and loaded, the stress states of the implant in different parts are different, and at the same time, sufficient permeability should be ensured inside the implant to guide blood vessel growth. Based on this design idea, the present invention provides a porous personalized mandibular implant that combines TPMS structural types with different performances and has controllable mechanical strength and permeability.

[0007] The technical solution adopted by the present invention to solve its technical problem is:

[0008] A method for manufacturing a mandibular porous structure implant with controllable functional gradient and promoting vascularization, the method comprising the following steps:

[0009] 1) Obtaining the native bone model of the implantation site:

[0010] 1.1) Collecting image data of the mandible of patients with mandibular lesions and reconstructing the image data in three dimensions using three-dimensional reconstruction software;

[0011] 1.2) Resection of the mandibular bone in the lesion area to obtain a bone tissue model of the mandibular bone in the defect area and a model of the remaining healthy mandibular bone after resection;

[0012] 1.3) Based on the mandibular model of the defect area, a finite element model was constructed, and the bite force was applied to the bone tissue to perform finite element calculations. The finite element calculation results showed that when the defective bone tissue was subjected to the bite force, different areas exhibited different stress states;

[0013] 2) Comparison of mechanical properties of different TPMS structures:

[0014] 2.1) The TPMS porous structure is based on a three-dimensional unit structure and is formed by spatial extension. The TPMS structure has four types: P, G, D, and IWP. Different types of TPMS models are generated by different mathematical formulas.

[0015] 2.2) Different bias values ​​C in the TPMS model correspond to different porosities, and the functional relationship between the design parameters of the porous structure and the porosity is constructed. A series of bias values ​​C with fixed intervals are taken to generate the corresponding three-dimensional model, and its porosity size is obtained in the model processing software, and the mathematical relationship between the C value and the porosity is fitted;

[0016] 2.3) The high-porosity TPMS porous structure is prone to "pinch-off" phenomenon, so the mathematical formula is improved to make the pore size and the connecting rod diameter more coordinated, effectively preventing the phenomenon of connecting rod being too thin or "pinch-off" and unsuccessful modeling; specifically: a function is introduced into the P structure surface function, which uses the IWP structure surface function, and by adjusting the coefficient value of the new constructor, the P structure surface is made more continuous and the connecting rod diameter is made more uniform;

[0017] 2.4) Use mathematical modeling software to generate a TPMS model with five cycles in the x-axis, y-axis, and z-axis directions. Control variables to generate multiple groups of homogeneous TPMS structural models of different types and different porosity sizes for finite element analysis; set the corresponding material properties and apply the corresponding mechanical loads to obtain the mechanical properties of different types of TPMS structures. Calculate the elastic modulus of the homogeneous TPMS structure at different porosities based on the finite element stress-strain data; adjust the unit parameters to match the elastic modulus of the TPMS structural unit with the elastic modulus of the bone tissue to obtain the TPMS bionic bone unit structure;

[0018] 3) Comparison of penetration performance of different TPMS structures:

[0019] Control variables to generate multiple groups of homogeneous TPMS structural models of different types and porosity sizes for seepage simulation, taking the permeability of natural bone as the target, and obtain the TPMS structural parameters under the target permeability;

[0020] 4) Fusion design of TPMS structural units with controllable functional gradient:

[0021] 4.1) Based on the finite element analysis results of the bite force applied to the defective bone tissue, a vascularized mandibular implant with controllable functional gradient is designed; the stress distribution results of the finite element results show a "sandwich structure";

[0022] 4.2) The top layer of the bone implant is selected to have a TPMS structure type with a compressive advantage, and the TPMS structural unit parameters are adjusted so that the mechanical properties of the adjusted bionic bone unit structure match the mechanical properties of the bone tissue; the middle layer of the bone implant is selected to have a TPMS type with good permeability and conducive to vascularization; the bottom layer of the bone implant is arranged with a TPMS type with a tensile advantage, and the TPMS structural unit parameters are adjusted so that the mechanical properties of the adjusted bionic bone unit structure match the mechanical properties of the bone tissue;

[0023] 4.3) Based on the different TPMS types and mathematical expressions used in the three-layer structure of the functional gradient implant, a sigmoid function is used to create a multi-morphological fusion TPMS structure, so that different types of porous structures can transition and fuse with each other, the speed of the transition part can be controlled, and different pore structures can be smoothly connected with a smooth surface.

[0024] Furthermore, the production method further comprises the following steps:

[0025] 5) Fabrication of a porous structure implant of mandibular bone with controllable functional gradient and vascularization: The personalized implant is made of titanium alloy material and is formed into a personalized implant in one step by additive manufacturing technology; the formed personalized implant needs to undergo surface treatment.

[0026] An implant made based on the design method is used for implanting into a defective part. The bionic bone tissue structure after fusion connection of different types of TPMS is topologically analyzed according to the defect shape of the implantation part to obtain a bone tissue implant model of the mandibular implant part. The left and right ends of the implant are respectively fitted with the cross-sections of the mandibular bone to be repaired.

[0027] The design concept of the present invention is: in the repair of segmental defects of the mandible, the implanted implant is subjected to compression at the top and tension at the bottom when subjected to occlusal force. Considering the important role of blood vessels in the growth of new bone tissue, it is planned to design and manufacture a vascularized mandibular implant based on TPMS functional gradient controllable based on titanium alloy material. At the same time, the pore parameters of the implant are controllable, which helps to guide new bone formation.

[0028] The beneficial effects of the present invention are as follows:

[0029] The personalized implant of the present invention is based on the TPMS unit, and is periodically extended in the XY plane. Different TPMS structure types and pore sizes are used in the z-axis direction according to the needs to achieve functional gradient changes. This design changes in the z-axis direction, which can effectively reduce the "stress shielding" effect, improve the connectivity of the pores, and control the permeability of the structure.

[0030] The overall permeability is within the range of natural bone, and the designed middle layer has a higher permeability than the top and bottom layers. At the same porosity, the permeability is increased by 56% compared with a homogeneous porous structure implant, which is beneficial for guiding angiogenesis inside the implant and promoting new bone growth.

[0031] At the same time, the TPMS pore structure with a high specific surface area has a curvature suitable for cell adhesion, which provides favorable conditions for cell proliferation. The pore structure can effectively conduct stress stimulation and avoid bone tissue absorption. The personalized implant has the same shape as the damaged part, matches the patient's mandible, and is conducive to restoring the patient's mandibular shape. Its application prospects in the field of mandibular defects are very promising. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 1 is a schematic diagram of a complete mandibular model of the present invention, wherein 11 is the initial structure of the implant, and 12 is a model of a non-lesion area;

[0033] Figure 2 There are different types of TPMS structural units;

[0034] Figure 3 It is a homogeneous TPMS structure model for porosity calculation and simulation;

[0035] Figure 4 is a schematic diagram of the bone scaffold in Example 1;

[0036] Figure 5 is a schematic diagram of the bone scaffold in Example 2;

[0037] Figure 6 is a schematic diagram of the bone scaffold in Example 3;

[0038] Figure 7 is a schematic diagram of the implant model;

[0039] Figure 8 It is a schematic diagram of the assembly of the implant model and the non-lesion area model. DETAILED DESCRIPTION

[0040] The present invention is further described below in conjunction with the accompanying drawings and specific implementation methods.

[0041] Reference Figure 1-Figure 6 A method for manufacturing a mandibular implant with a vascularized structure controlled by a TPMS functional ladder comprises the following steps:

[0042] Step 1) Extraction of mandibular model:

[0043] 1.1) The patient's mandibular image data is collected, and the image data is imported into the image processing software to perform a three-dimensional reconstruction of the mandibular model, and the lesion area is removed to obtain the defect area.

[0044] 1.2) Mirror the contralateral mandible to the defect area to obtain a complete mandibular model and the separated initial structure of the implant. Figure 1 As shown, 11 is the initial structure of the implant, and 12 is the mandibular bone model of the remaining non-lesion area.

[0045] 2) Analysis of the performance of TPMS porous structure:

[0046] 2.1) The TMPS porous structure is based on a three-dimensional unit structure and is formed by extending several cycles in space. The TPMS porous structure can be modeled by Mathematica software. Figure 2 a is a P-type TMPS structure, Figure 2 b is the G type TPMS structure, Figure 2 c is the D type TPMS structure, Figure 2 d is the TPMS structure of IWP type. The above four structures are all entities formed by the equivalent plane of the TPMS formula biased in one direction. When the equivalent plane is biased in two directions, the following is formed Figure 2 The layered structure shown in e, Figure 2 e is a layered P structure entity formed by the P-type TPMS equivalent planes offset in two directions. Due to different modeling methods, the layered P structure has different performances in mechanical properties and permeability.

[0047] 2.2) Modeling was performed in Mathematica software. The established model was a porous structure with five periods in the x-axis, y-axis, and z-axis directions. The corresponding porous structures were derived after taking different offset values ​​C with an interval of 0.1. The corresponding porosity was calculated in the model processing software, such as Magics or Rhinoceros. In the data fitting software, such as Origin, the linear relationship between porosity and C was fitted. Thus, the porosity can be controlled by changing the offset value C.

[0048] 2.3) According to the above steps, when the porosity requirement is relatively high, the P structure is modeled, and the connecting rod of the P structure will be "pinched off" and the modeling cannot be successful. After optimizing and improving the mathematical formula of the P structure, the "pinched off" phenomenon is improved, such as Figure 3 f. The P-type porous structure with improved function optimization makes the connecting rods more uniform and less prone to "pinching off".

[0049] 2.4) According to the above steps, the corresponding bias value C at different porosities is taken for modeling. In Mathematica software, five cycles of extension are performed on each TPMS unit in the x-axis, y-axis, and z-axis directions to form a homogeneous porous structure for finite element simulation analysis. Figure 3 The models exported from Mathematica are in STL format, and after checking the quality of the triangular facets, INP format files that can be imported into Abaqus software are generated. In Abaqus software, the corresponding material properties and boundary conditions are set, and the corresponding mechanical loads are applied after setting the analysis steps to complete the establishment of the finite element model.

[0050] 2.5) According to the above steps, the corresponding bias value C is taken for different porosities for modeling. The modeling is programmed in Mathematica software, and each TPMS unit is extended for five cycles in the x-axis, y-axis, and z-axis directions to form a homogeneous porous structure for seepage simulation analysis. After checking the quality of the triangular facets, an MPHTXT format file that can be imported into Comsol software is generated. The permeability is calculated after applying the corresponding boundary conditions in Comsol software.

[0051] 2.6) Obtain stress-strain data based on finite element results, calculate elastic modulus using stress-strain data in the elastic region, and determine the porosity range corresponding to the elastic modulus matching natural bone tissue. Determine the porosity range corresponding to the permeability matching natural bone tissue based on the permeability results obtained. Combine the elastic modulus and permeability range of the porous structure to comprehensively determine the porosity of the porous structure.

[0052] 3) Design of implants with controllable functional gradient:

[0053] Based on the requirements of the functional gradient implant, different TPMS structures with different advantages are selected. Different TPMS structures have different mathematical expressions. The use of spatial weight functions can create multi-modal fusion TPMS structures, such as sigmoid functions, so that different types of porous structures can be transitioned and fused. The urgency of the transition part can be changed according to the coefficient K in the function to achieve the purpose of smoothly connecting different pore structures and smoothing the surface.

[0054] Embodiment 1:

[0055] like Figure 4 As shown, this embodiment is a functional gradient controllable pro-vascularized bone scaffold constructed with a layered P surface structure as the top layer, a function-optimized P surface structure as the middle layer, and a G surface structure as the bottom layer, and the type of porous structure changes gradually in the z-axis direction. The layered P surface structure has excellent compressive resistance. As the top porous structure of the bone scaffold, it can increase the compressive resistance of the bone scaffold as a whole. The G surface structure has excellent tensile resistance. When the implant is subjected to a bite force, the bottom layer will be subjected to tensile stress; the G surface structure, as the bottom porous structure of the bone scaffold, can increase the tensile resistance of the bone scaffold as a whole. The functional gradient porous structure realizes the change of the pore structure type as the spatial position changes, thereby realizing the role of functional zoning. The porosity, permeability, and elastic modulus of each structure type can be controlled by changing the parameters of each structure type.

[0056] Embodiment 2:

[0057] like Figure 5As shown, this embodiment is a functional gradient controllable pro-vascularized bone scaffold constructed with a layered P surface structure as the top layer, a function-optimized P surface structure as the middle layer, and an IWP surface structure as the bottom layer. The type of porous structure changes gradually in the z-axis direction. The layered P surface structure has excellent compressive resistance. As the top porous structure of the bone scaffold, it can increase the compressive resistance of the bone scaffold as a whole. The IWP surface structure has excellent compressive and tensile properties. When the implant is subjected to a bite force, the bottom layer will be subjected to tensile stress; the IWP surface structure, as the bottom porous structure of the bone scaffold, can increase the tensile resistance of the bone scaffold as a whole. The functional gradient porous structure realizes the change of the pore structure type as the spatial position changes, thereby realizing the role of functional zoning. The porosity, permeability, and elastic modulus of each structure type can be controlled by changing the parameters of each structure type.

[0058] Embodiment 3:

[0059] like Figure 6 As shown, in this embodiment, the IWP curved surface structure is used as the top and bottom structures of the bone scaffold, and the P curved surface structure after function optimization is used as the middle layer to construct a functional gradient controllable vascularized bone scaffold. The IWP curved surface structure has excellent compressive and tensile properties, and the entire "sandwich" structure has the same watershed. The bone scaffold has extremely high pore connectivity and biopermeability. The functional gradient porous structure realizes the change of pore structure type as the spatial position changes, realizing the role of functional zoning. The porosity, permeability, and elastic modulus of each structure type can be controlled by changing the parameters of each structure type.

[0060] The middle layer of the above-mentioned examples all adopts a function-optimized P-surface structure, which has the most excellent permeability, meets the needs of the functional area for transporting nutrients and metabolic waste, and promotes angiogenesis.

[0061] like Figure 7 As shown, the above functional gradient porous structure is subjected to Boolean operation with the defective mandibular bone to obtain a personalized porous structure implant. Referring to the thickness standard of the reconstructed titanium plate, the appropriate position on the mandibular surface is selected to thicken by 3mm to form an implant fixing structure 71. The titanium nail refers to the standard titanium nail specifications, with a major diameter of 2.7mm; to avoid the titanium nail head being exposed outside the fixing plate, the hole on the fixing plate is designed as a countersunk hole 73; referring to the reconstructed titanium plate, the hole spacing is 8mm, and in order to avoid more surgical damage, only two fixing nails are used. A boss 72 with a height of about 5mm and a width of about 2mm is set at both ends of the top of the implant to increase the contact surface area with the native mandibular bone. In addition, it can play a supporting role under the action of the bite force, making the implant more stable.

[0062] In addition, the above examples are all integrally formed using additive manufacturing technology.

[0063] The implant is based on the mechanical environment during occlusion and effectively restores the patient's chewing function. It has appropriate permeability to meet the permeability requirements for capillary growth and metabolism. During occlusion, stress can be effectively transmitted to the inside of the porous structure, giving cells the stress stimulation required for growth and achieving bone cell proliferation.

Claims

1. A method for designing a mandibular implant with controllable functional gradient and vascularization, characterized in that: The following steps are involved: Step 1) obtaining a native bone model of the implantation site; Step 2) There are four types of TPMS structures: P, G, D, and IWP. Compare the mechanical properties of different TPMS structure models; Step 3) Comparing the permeability performance of different TPMS structural models: controlling variables to generate multiple groups of homogeneous TPMS structural models of different types and different porosity sizes for permeation simulation, taking the permeability of natural bone as the target, and obtaining the TPMS structural parameters under the target permeability; Step 4) Fusion design of TPMS structural units with controllable functional gradient: 4.1) Based on the finite element analysis results of the bite force applied to the defective bone tissue, a multi-morphological fusion TPMS structure with smooth connection is created using a spatial weight function, and topologically combined with the personalized shape of the natural mandible to obtain a vascularized mandibular implant with controllable functional gradient; 4.2) The top layer of the bone implant uses a TPMS structure type with a compression advantage, and the TPMS structural unit parameters are adjusted so that the mechanical properties of the adjusted bionic bone unit structure match the mechanical properties of the bone tissue; the bottom layer of the bone implant uses a TPMS type with a tensile advantage, and the TPMS structural unit parameters are adjusted so that the mechanical properties of the adjusted bionic bone unit structure match the mechanical properties of the bone tissue; the middle layer of the bone implant uses a TPMS type with a permeability advantage, and the TPMS structural unit parameters are adjusted so that the permeability of the adjusted bionic bone unit matches the permeability of the bone tissue; 4.3) Use the sigmoid function to create a multi-morphological fusion TPMS structure, so that different types of porous structures can transition and fuse with each other, and different pore structures can be smoothly connected to make the surface smooth.

2. The method for designing a mandibular implant with controllable functional gradient and vascularization according to claim 1, characterized in that: The process of step 1) is as follows: 1.1) Obtaining mandibular imaging data of patients with mandibular lesions, and reconstructing the imaging data in three dimensions using three-dimensional reconstruction software; 1.2) Obtaining the bone tissue model of the mandibular defect area and the remaining healthy mandibular model after resection; 1.3) Based on the mandibular model of the defect area, a finite element model was constructed, and the bite force was applied to the bone tissue to perform finite element calculations.

3. The method for designing a mandibular implant with controllable functional gradient and promoting vascularization according to claim 1, characterized in that: The process of step 2) is as follows: 2.1) Constructing the functional relationship between the design parameters of the porous structure and the porosity: taking a series of offset values ​​C with fixed intervals to generate the corresponding three-dimensional model, obtaining its porosity in the model processing software, and fitting the mathematical relationship between the C value and the porosity; 2.2) Improve the mathematical formula to make the aperture and the connecting rod diameter more coordinated; specifically: introduce a function into the P structure surface function, which uses the IWP structure surface function, and adjust the coefficient value of the new constructor to achieve a more continuous P structure surface and a more uniform connecting rod diameter; 2.3) Generate a TPMS model with five periods in the x-axis, y-axis, and z-axis directions, and control variables to generate multiple groups of homogeneous TPMS structure models of different types and different porosity sizes for finite element analysis; set corresponding material properties and apply corresponding mechanical loads to obtain the mechanical properties of different types of TPMS structures; 2.4) Calculate the elastic modulus of the homogeneous TPMS structure at different porosities based on the finite element stress-strain data; The unit parameters are adjusted to make the elastic modulus of the TPMS structural unit match the elastic modulus of the bone tissue, thereby obtaining the TPMS bionic bone unit structure.

4. The method for designing a mandibular implant with controllable functional gradient and promoting vascularization according to claim 1, further comprising the following steps: Step 5) Fabrication of a porous structure implant of mandibular bone with controllable functional gradient and vascularization: using titanium alloy material and additive manufacturing technology to form a personalized implant in one go; and performing surface treatment on the formed personalized implant.

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