CN114504677B - 3D printing skull repairing titanium mesh and preparation method thereof - Google Patents
3D printing skull repairing titanium mesh and preparation method thereof Download PDFInfo
- Publication number
- CN114504677B CN114504677B CN202210024488.6A CN202210024488A CN114504677B CN 114504677 B CN114504677 B CN 114504677B CN 202210024488 A CN202210024488 A CN 202210024488A CN 114504677 B CN114504677 B CN 114504677B
- Authority
- CN
- China
- Prior art keywords
- titanium mesh
- printing
- skull
- mesh
- hydroxyapatite
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Images
Classifications
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- Structural Engineering (AREA)
- Neurosurgery (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The invention particularly relates to a 3D printing skull repairing titanium mesh and a preparation method thereof, belonging to the technical field of biomedical materials, and the method comprises the following steps: analyzing the head to be repaired to obtain skull defect part information; 3D printing is carried out according to the skull defect part information to obtain a titanium mesh skull model; adding the titanium mesh skull model into a dopamine solution to obtain a polydopamine microsphere modified titanium mesh skull model; dissolving type I collagen in a solvent to obtain a gel solution; mixing hydroxyapatite and the gel solution to obtain 3D printing biological ink; and printing the 3D printing biological ink on the polydopamine microsphere modified titanium mesh skull model, and performing post-treatment to obtain the repaired titanium mesh. By combining the 3D printing titanium mesh with the hydroxyapatite/collagen guided tissue regeneration layer, the surface roughness and the bioactivity of the titanium mesh material can be increased, the combination of the material and bone is promoted, the adhesion and proliferation of cells and the induction of bone formation are promoted, and the repair and healing of skull tissue are accelerated.
Description
Technical Field
The invention belongs to the technical field of biomedical materials, and particularly relates to a 3D printing skull repairing titanium mesh and a preparation method thereof.
Background
Skull defects are a common secondary disease in clinic. Mainly seen in various traumas and postoperations, such as electric shock injury, car accident injury, bullet injury, skull malignant tumor excision, congenital malformation, after craniotomy decompression, and the like. In principle, skull defects with the maximum diameter of more than 3cm need to be subjected to skull reconstruction surgery, and when the skull defects exceed 3cm, clinical symptoms can be generated. Successful skull reconstruction needs to meet 3 requirements: (1) maintaining the integrity of the dura mater, i.e. the protection of the brain; (2) The barrier between the cranium and the outside is protected, namely the biology and the materials are stable; (3) Maintaining the normal dome-like shape of the head, i.e. aesthetic requirements.
The ideal skull defect repair material satisfies the following characteristics: (1) the acquisition is convenient; (2) high biocompatibility; (3) the defect part can be completely matched, and the ductility is good; (4) Good biomechanical performance, brain barrier protection and external force resistance; (5) has osteogenesis inducing potential; (6) compatibility of image examination of the skull; (7) resistance to infection.
At present, the skull repairing materials applied to clinic mainly comprise autogenous bones, allogeneic bones, xenogeneic bones and artificial materials.
Autologous bone repair is the gold standard for skull reconstruction. The autologous bone tissue has good osteoconductivity and histocompatibility, no immune rejection reaction and low postoperative femoral leakage rate, but has the problems of limited supply area, difficult molding, increased secondary trauma, higher bone absorption rate of transplanted bone and the like, and the clinical application is limited.
The allogeneic bone is generally subjected to special sterilization treatment, does not have common infectious diseases and has no immunogenicity. Allogeneic bone may be surgically biologically combined with autologous tissue, allowing for vascularization of the tissue and in-growth reconstruction of autologous tissue. However, the clinical application of the allogeneic bone on the skull defect is limited by the high infection rate after the operation, the absorption rate of the transplanted bone, religious and ethical factors and the like.
The source of xenogenic bone is rich, but the immunogenicity is strong, the freeze-dried bone, calcined bone and deproteinized bone used clinically are obtained by respectively carrying out freeze-drying, high-temperature calcination, irradiation, decalcification and other treatments on animal bone tissues, so that organic components such as cells, collagen and the like are removed, a natural pore structure is maintained, the antigenicity is eliminated, but the tissue has small mechanical strength, is loose and fragile, has poor mechanical strength and reduces the plasticity.
The clinical common artificial skull repairing materials mainly comprise hydroxyapatite, polymethyl methacrylate, polyether-ether-ketone, titanium mesh and the like.
The hydroxyapatite has good biocompatibility, osteoconductivity and osteoinductivity, and after being implanted into a body, calcium and phosphorus can be liberated from the surface of the material and absorbed by body tissues, and new bone tissue growth is induced. However, the hydroxyapatite is easy to break under the action of external force after operation, the infection rate after operation is high, and in addition, the hydroxyapatite is degraded too fast in vivo and is usually used for repairing small-area bone defects left by cranial bone drilling, and the large-area bone defects need to be fixed by a titanium mesh.
The polymethyl methacrylate has light weight, low price and strong plasticity, can be instantly molded according to the shape of the bone defect, and is firmly fixed. The main defects of polymethyl methacrylate are that the material is crisp, the polymethyl methacrylate is easy to crack under the action of external force, certain thermal damage is caused to surrounding tissues in the curing process in the operation, and the probability of postoperative infection and exposure is high.
Polyether ether ketone (PEEK) is a wholly aromatic semi-crystalline thermoplastic polymer material, has good biocompatibility, wear resistance and stable chemical characteristics, and can be sterilized by high-temperature steam or gamma irradiation. The polyether-ether-ketone has strong plasticity, and the elasticity, strength, heat insulation property, stability and other aspects of the polyether-ether-ketone are equivalent to those of the autogenous skull, so that the rejection reaction is generally avoided. The X-ray can penetrate through the magnetic material, has no magnetism, has no artifact in CT or MRI images, and does not influence the postoperative image analysis of patients. However, the melting point of polyetheretherketone is very high (the glass transition temperature is 143 ℃ C., the melting point reaches 343 ℃ C.), which makes its processing extremely difficult. In addition, the PEEK rapid forming piece manufactured by simply adopting 3D printing is loose in material, the mechanical property cannot meet the medical requirement, the operation cost of the PEEK individualized skull is high, and the application of the PEEK rapid forming piece in the individualized skull repair operation is limited.
The titanium net has the advantages of good biocompatibility and physical and chemical properties, strong plasticity, no magnetism and the like, and can resist secondary trauma. After being implanted, the fibroblasts can grow into micropores of the titanium mesh, so that the titanium mesh and tissues are integrated, and the titanium mesh has the tendency of calcification and ossification, does not influence X-ray examination and electroencephalogram examination of the skull, has good hand feeling, is uniform and beautiful, and is widely applied to the field of clinical skull defect repair.
The titanium net that uses clinically is mostly finished product titanium net, and it can maintain stable spatial structure and mechanical properties, nevertheless need tailor again and moulding according to the defect condition of difference, needs to repeat many times usually to moulding often the error is great by hand, and the prosthetic repair of preparation agrees with the nature relatively poor, and the precision is lower, can not reach the effect of matching completely, in addition easily forms sharp edge at moulding in-process, has increased the risk that the postoperative titanium net exposes. However, the single titanium mesh belongs to a biological inert material, has no biological activity, cannot be rapidly fused with soft tissues, and cannot effectively promote the repair and regeneration of bone tissues. In addition, the expansion with heat and contraction with cold and the quick heat conduction of the titanium mesh are simply used, so that the problems of sensitivity to cold and heat, irritation, related complications and the like of the scalp, the dura mater and the surrounding skull are solved.
Disclosure of Invention
The application aims to provide a 3D printing skull repairing titanium mesh and a preparation method thereof, and aims to solve the problem that a finished product titanium mesh cannot be rapidly fused with soft tissues when the existing titanium mesh is used alone.
The embodiment of the invention provides a preparation method of a 3D printing skull repairing titanium mesh, which comprises the following steps:
analyzing the head to be repaired to obtain skull defect part information;
3D printing is carried out according to the skull defect part information to obtain a titanium mesh skull model;
adding the titanium mesh skull model into a dopamine solution to obtain a polydopamine microsphere modified titanium mesh skull model;
dissolving type I collagen in a solvent to obtain a gel solution;
mixing hydroxyapatite with the gel solution to obtain 3D printing biological ink;
and printing the 3D printing biological ink on the polydopamine microsphere modified titanium mesh skull model according to the skull defect position information, and performing post-treatment to obtain the 3D printing skull repair titanium mesh, wherein the post-treatment comprises freeze drying, crosslinking, an analysis process and cobalt 60 25kGy dosage irradiation sterilization.
Optionally, the method for obtaining the poly-dopamine microsphere modified titanium mesh skull model specifically comprises the following steps:
dissolving tris (hydroxymethyl) aminomethane powder in deionized water, titrating with dilute hydrochloric acid to adjust the pH value to 7.5-10, dissolving dopamine hydrochloride powder in tris (hydroxymethyl) aminomethane solution, mixing and stirring for 30-120 min to form dopamine solution;
adding the titanium mesh skull model into a dopamine solution, carrying out magnetic stirring reaction for 24-48 h at room temperature, repeatedly washing the polydopamine microsphere modified titanium mesh with pure water for 2-3 times, and drying in a forced air drying oven at 37-52 ℃ for 12-24 h to obtain the polydopamine microsphere modified titanium mesh skull model.
Optionally, the thickness of the titanium mesh skull model is 0.4 mm-10 mm, and the mesh diameter of the titanium mesh skull model is 0.4 mm-0.8 mm; the mass concentration of the dopamine in the dopamine solution is 0.1-20 mg/mL; 0.5 g-3 g of type I collagen is contained in each 100mL of the 3D printing biological ink; every 100mL of the 3D printing biological ink contains 0.5g to 1.5g of hydroxyapatite, the hydroxyapatite is medical-grade nano hydroxyapatite, and the particle size of the medical-grade nano hydroxyapatite is 50nm to 150nm.
Optionally, the solvent is an acetic acid solution, and the concentration of the acetic acid solution is 0.03mol/L-0.07mol/L.
Optionally, the 3D printing biological ink is printed on the titanium mesh skull model, and the printing parameters of the low-temperature 3D printing biological ink are set as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: -4 to 10 ℃, air pressure: 5-300 kpa, mesh diameter 0.4-0.8 mm, printing thickness: 2-4 mm, and the diameter of the needle of the equipment is 0.4mm.
Optionally, the freeze drying comprises a pre-freezing process and a freeze drying process, wherein the freezing temperature of the pre-freezing process is-80 ℃ to-20 ℃, the pre-freezing time of the pre-freezing process is 3h to 24h, the freezing temperature of the freeze drying process is-50 ℃ to 37 ℃, the pressure of the freeze drying process is 0.1Pa to 50Pa, and the freezing time of the freeze drying process is 24h to 72h.
Optionally, the crosslinking process comprises a glutaraldehyde steam crosslinking process and a heat crosslinking process, wherein the glutaraldehyde steam crosslinking is carried out in a closed container at a crosslinking temperature of 37-52 ℃, the volume concentration of glutaraldehyde steam crosslinked by glutaraldehyde steam is 5-25%, and the time for glutaraldehyde steam crosslinking is 2-12 h; the thermal crosslinking is carried out in a vacuum drying oven at the temperature of 100-110 ℃ and the pressure of 10-150 Pa for 12-48 h.
Optionally, the analysis process is that the analysis temperature is 37-52 ℃ in a forced air drying oven, and the analysis time is 2-4 d.
Based on the same inventive concept, the embodiment of the invention also provides a 3D printing skull repairing titanium mesh, and the skull repairing titanium mesh is prepared by adopting the preparation method of the 3D printing skull repairing titanium mesh.
One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:
the embodiment of the invention provides a preparation method of a 3D printing skull repairing titanium mesh, which comprises the following steps: analyzing the head to be repaired to obtain skull defect part information; 3D printing is carried out according to the skull defect part information to obtain a titanium mesh skull model; adding the titanium mesh skull model into a dopamine solution to obtain a polydopamine microsphere modified titanium mesh skull model; dissolving type I collagen in a solvent to obtain a gel solution; mixing hydroxyapatite and a gel solution to obtain 3D printing biological ink; and (3) printing the 3D printing biological ink on a polydopamine microsphere modified titanium mesh skull model according to the skull defect part information, and performing post-treatment to obtain the repaired titanium mesh. By combining the 3D printing titanium mesh with the hydroxyapatite/collagen guided tissue regeneration layer, the surface roughness and the bioactivity of the titanium mesh material can be increased, the combination of the material and bone is promoted, the adhesion and proliferation of cells and the induction of bone formation are promoted, and the repair and healing of skull tissue are accelerated.
The foregoing description is only an overview of the technical solutions of the present invention, and the embodiments of the present invention are described below in order to make the technical means of the present invention more clearly understood and to make the above and other objects, features, and advantages of the present invention more clearly understandable.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on the drawings without creative efforts.
Fig. 1 is a flow chart of a method provided by an embodiment of the invention.
Detailed Description
The present invention will be described in detail below with reference to specific embodiments and examples, and the advantages and various effects of the present invention will be more clearly apparent therefrom. It will be understood by those skilled in the art that these specific embodiments and examples are for the purpose of illustrating the invention and are not to be construed as limiting the invention.
Throughout the specification, unless otherwise specifically noted, terms used herein should be understood as having meanings as commonly used in the art. Accordingly, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. If there is a conflict, the present specification will control.
Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods.
In order to solve the technical problems, the general idea of the embodiment of the application is as follows:
the applicant finds in the course of the invention: the 3D printing titanium mesh technology is applied to skull repair, so that the problems of plasticity and compatibility of a repair material are solved, the processing speed is high, and the waiting time of a patient is reduced; the porous through structure of the human-like skeleton can effectively overcome the problems of stress shielding and low biological activity commonly existing in the implant, and simultaneously can minimize the heat dissipation in the cranial cavity and maintain the normal heat conduction level. However, the single 3D printing titanium mesh belongs to a biological inert material, has no biological activity, cannot be rapidly fused with soft tissues, and cannot effectively promote the repair and regeneration of bone tissues.
According to an exemplary embodiment of the invention, a 3D printing method for preparing a skull repairing titanium mesh is provided, which includes:
s1, analyzing a head to be repaired to obtain skull defect part information;
specifically, first, CT scout and enhancement scans are performed on the head defect site, and then three-dimensional reconstruction is performed to determine the position, size, shape, etc. of the head skull defect.
S2, performing 3D printing according to the skull defect part information to obtain a titanium mesh skull model;
pouring the scanning data into software to design a bone defect model, storing the bone defect model in an STL format, importing the bone defect model into a 3D printer, correcting and calibrating the bone defect model by using the software, molding by using digital equipment according to the data of the model, and manufacturing a titanium mesh matched with the defect part, wherein the edge of the titanium mesh is 1cm higher than the edge of the defect. The chemical components of the pure titanium prosthesis accord with the GB/T13810-2017 Standard of titanium and titanium alloy processing materials for surgical implants.
In some embodiments, the 3D printing titanium mesh is integrally formed, the edge of the titanium mesh is provided with 3 to 4 integrated protruding blocks, and the end of each protruding block is provided with a titanium nail hole. The thickness of the titanium net is 0.4 mm-10 mm, and the diameter of the mesh is 0.4 mm-0.8 mm.
The reason for controlling the thickness of the titanium mesh to be 0.4 mm-10 mm is to better meet the requirement of clinical application of skull repair, the adverse effect of overlarge thickness value is that the combination of materials and soft and hard tissues cannot be effectively promoted, osteogenesis cannot be effectively induced, the adverse effect of undersize value is that sharp edges are easily formed, and the risk of exposure of the titanium mesh after operation is increased.
The reason for controlling the diameter of the mesh to be 0.4 mm-0.8 mm is favorable for the adhesion of osteoblasts and the growth of new bones and accelerating the repair and healing of cranial tissues, the problem that the leakage of soft tissue fluid and related complications are caused by the overlarge diameter is solved, and the problem that the growth of soft and hard tissues, particularly the growth of new bones is not favorably realized by the undersize adverse effect.
S3, obtaining the polydopamine microsphere modified titanium mesh skull model, which specifically comprises the following steps:
dissolving trihydroxymethyl aminomethane powder in deionized water, titrating with dilute hydrochloric acid to adjust the pH to 7.5-10, dissolving dopamine hydrochloride powder in the trihydroxymethyl aminomethane solution, mixing and stirring for 30-120 min to form a dopamine solution; the mass concentration of the dopamine in the dopamine solution is 0.1-20 mg/mL; dopamine can undergo oxidative polymerization in an alkaline (pH is more than 7.5) aerobic environment to form polydopamine nano microspheres, the dopamine gradually undergoes self-polymerization to form polydopamine along with the increase of the pH, and the color gradually changes from light brown to dark brown;
adding the titanium mesh skull model into a dopamine solution, carrying out magnetic stirring reaction for 24-48 h at room temperature, repeatedly washing the polydopamine microsphere modified titanium mesh with pure water for 2-3 times, and drying in a forced air drying oven at 37-52 ℃ for 12-24 h to obtain the polydopamine microsphere modified titanium mesh skull model.
S4, dissolving the type I collagen in a solvent to obtain a gel solution;
s5, mixing the hydroxyapatite with the gel solution to obtain 3D printing biological ink;
specifically, the preparation of the 3D printing bio-ink comprises: adding medical grade nano hydroxyapatite into the I type collagen gel solution dissolved in the acetic acid solution, and stirring to obtain the 3D printing biological ink.
In some embodiments, the medical grade nano hydroxyapatite has a particle size of 50 to 150nm, an acetic acid concentration of 0.05mol/L, a hydroxyapatite concentration of 0.5 to 1.5g/100mL in the bio-ink, and a type I collagen concentration of 0.5 to 3g/100mL.
The hydroxyapatite is used as a main component of natural bone inorganic salt, has good bone conductivity and biocompatibility, is considered as an ideal material for bone defect repair, particularly the nano-scale hydroxyapatite is similar to inorganic components in natural bones, can be introduced into a skull repair material to have great superiority in the aspects of mechanics and biology, is beneficial to the growth of new bone tissues and vascular tissues, and the reason for controlling the particle size of the hydroxyapatite to be 50-150 nm is that the material is easy to obtain, has good mechanical property and bone conductivity, and better meets the requirements of clinical application of skull repair, and the overlarge particle size is not beneficial to the adhesion of the hydroxyapatite on a guide tissue regeneration layer, and influences the 3D printing molding of 3D printing biological ink on a titanium mesh, influences the mechanical property of the guide tissue regeneration layer, and the hydroxyapatite with the undersize particle size is easy to agglomerate and influences the mechanical property of the guide tissue regeneration layer; the reason for controlling the concentration of the hydroxyapatite to be 0.5-1.5 g/100mL is that the material better meets the requirements of clinical application of skull restoration in the aspects of mechanics and biology, the adverse effect of over-low concentration value is to influence the osteoconductivity of a guided tissue regeneration layer and the ingrowth of new bone tissues, and the adverse effect of over-high concentration value is to be unfavorable for 3D printing and forming of biological ink on a titanium mesh by 3D printing, so that the material for forming the guided tissue regeneration layer has high brittleness and the mechanical strength is difficult to meet the requirements.
The type I collagen is a main structural protein of the spinal animals, is extracellular matrix secreted by osteoblasts in the osteogenesis process, is a scaffold deposited by calcium salt, is an accelerant of a bone matrix double layer and is a double-layer template; can promote cell migration, adsorption and differentiation and regulate cell growth, is approved by the FDA in the United states as a biological material, and has a series of collagen bone implant products. The type I collagen has the advantages of low immunogenicity, no toxic or side effect of in vivo degradation products and the like, but has poor mechanical property and high degradation rate. The silk fibroin has excellent biocompatibility and biodegradability and better mechanical property, is easy to sterilize and shape, is widely applied to the aspects of ligament tissue repair, vascular tissue transplantation, cartilage tissue repair, skin tissue regeneration, nerve tissue engineering and the like, but has mechanical strength far lower than that of bone tissue, and the simple silk fibroin has too slow degradation speed. The nano-hydroxyapatite has good bone conductivity and biocompatibility, but the single hydroxyapatite has larger brittleness and low toughness. Therefore, the hydroxyapatite, the type I collagen and the silk fibroin are used in a compounding way, the problem of insufficient performance of a single material can be solved, the advantage complementation of various materials is realized, the obtained skull repairing membrane has good mechanical property and controllable biodegradation time, the reason for controlling the concentration of the type I collagen to be 0.5-3 g/100mL is that the solution is easy to prepare, the material better meets the requirement of clinical application of skull repairing, the type I collagen with overlarge value is slowly dissolved, the aperture of the prepared guide tissue regeneration layer material is small, the soft and hard tissues are not favorable to growing in, the skull tissue repairing healing is influenced, and the prepared guide tissue regeneration layer material with the overlong value has low mechanical strength and high degradation speed and is difficult to meet the requirement of the clinical application of the skull repairing.
S6, printing the 3D printing biological ink on the titanium mesh skull model according to the skull defect position information, and performing post-treatment, wherein the post-treatment comprises freeze drying, crosslinking, an analysis process and cobalt 60 25kGy dosage irradiation sterilization to obtain the 3D printing skull repair titanium mesh.
Specifically, the confirmed skull defect three-dimensional reconstruction model is corrected, printing parameters are set, and a hydroxyapatite/collagen guided tissue regeneration layer is printed on the printed titanium mesh by the obtained hydroxyapatite/collagen biological ink in a 3D mode.
In some embodiments, the printing parameters for low temperature 3D printing of the hydroxyapatite/collagen bio-ink are set as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: -4 to 10 ℃, air pressure: 5-300 kpa, mesh diameter 0.4-0.8 mm, printing thickness: 2-4 mm, and the diameter of the needle of the equipment is 0.4mm.
The freeze-drying includes a pre-freezing process and a freeze-drying process, and in some embodiments, the freeze-drying process conditions are as follows: pre-freezing for 3-24 h at-20 to-80 ℃, and then drying the frozen body for 24-72 h at-50 to 37 ℃ and under the pressure of 0.1 to 50 Pa.
The reason for controlling the pre-freezing temperature to be-20 to-80 ℃ and the time to be 3 to 24 hours is to meet the actual equipment parameters of the freeze dryer and the freeze-drying process requirements of products, the pre-freezing temperature is higher, the pre-freezing time is longer, the pre-freezing temperature is lower, the equipment temperature parameters can not reach, and the product structure of the subsequent freeze-drying process can also be influenced.
The reason for controlling the freeze drying temperature to be-50-37 ℃, the pressure intensity to be 0.1-50 Pa and the time to be 24-72 h is to meet the actual freeze dryer equipment parameters and the product freeze-drying process requirements, the freezing temperature is higher, the freezing time is longer, the freezing temperature is lower, the freezing speed is too high, and the product structure of the subsequent freeze-drying process is influenced.
The crosslinking process includes a glutaraldehyde steam crosslinking process and a thermal crosslinking process, and in some embodiments, the process conditions of glutaraldehyde steam crosslinking are as follows: crosslinking for 2-12 h in a closed container at 37-52 ℃ and 5-25% of glutaraldehyde steam concentration; the thermal crosslinking is carried out in a vacuum drying oven at the temperature of 100-110 ℃ under the pressure of 10-150 Pa for 12-48 h.
The reason that the temperature of glutaraldehyde steam crosslinking is controlled to be 37-52 ℃, the volume concentration of glutaraldehyde steam is controlled to be 5-25%, and the time is 2-12 h is that the volume concentration of glutaraldehyde steam is too large to reach, the volume concentration of glutaraldehyde steam is too low, the crosslinking temperature is low, and the crosslinking time is too long.
The reason for controlling the thermal crosslinking temperature to be 100-110 ℃, the pressure to be 10-150 Pa and the crosslinking time to be 12-48 h is that the thermal crosslinking temperature is low, the crosslinking time is long, and the thermal crosslinking temperature is high, so that the structural performance of the product is influenced.
In some embodiments, the resolution process conditions are: the analysis temperature is 37-52 ℃, and the analysis time is 2-4 d.
The analysis temperature is controlled to be 37-52 ℃, and the analysis time is controlled to be 2-4 d, because the analysis temperature is low, the analysis time is long, and the analysis temperature is high, so that the structural performance of the product is influenced.
The 3D printed skull repairing titanium mesh and the preparation method thereof according to the present application will be described in detail below with reference to examples, comparative examples, and experimental data.
Example 1
A preparation method of a 3D printing skull repairing titanium mesh comprises the following steps:
s1, preparing a 3D printing titanium mesh. Firstly, performing CT flat scanning and enhanced scanning on a head defect part, then performing three-dimensional reconstruction, and determining the position, size, shape and the like of the head skull defect; pouring the scanning data into software to design a bone defect model, storing the bone defect model in an STL format, importing the bone defect model into a 3D printer, correcting and calibrating the bone defect model by using the software, molding by using digital equipment according to the data of the model, and manufacturing a titanium mesh matched with the defect part, wherein the edge of the titanium mesh is 1cm higher than the edge of the defect. The chemical components of the pure titanium prosthesis accord with the standard of GB/T13810-2017 titanium and titanium alloy processing materials for surgical implants; 3D prints titanium net and is integrated into one piece, and the titanium net edge sets up 4 pieces of integration protrusion pieces, and protrusion piece end is equipped with titanium nail hole. The thickness of the titanium mesh is 0.4mm, and the diameter of the mesh is 0.6mm.
S2, preparing the polydopamine microsphere modified titanium mesh. Dopamine can undergo oxidative polymerization in an alkaline (pH is more than 7.5) aerobic environment to form polydopamine nano-microspheres. Preparing a dopamine solution: dissolving 0.121g of tris (hydroxymethyl) aminomethane powder in 100mL of deionized water, titrating with dilute hydrochloric acid to adjust the pH value to 8.5, dissolving 200mg of dopamine hydrochloride powder in tris (hydroxymethyl) aminomethane solution, mixing and stirring for 60min to form dopamine solution. Adding the titanium mesh obtained or prepared in advance into a dopamine solution, carrying out magnetic stirring reaction for 36 hours at room temperature, repeatedly washing the polydopamine microsphere modified titanium mesh for 2-3 times by using pure water, and drying the polydopamine microsphere modified titanium mesh for 24 hours in a forced air drying oven at 40 ℃.
And S3, low-temperature 3D printing of a hydroxyapatite/collagen guided tissue regeneration coating. Firstly, preparing hydroxyapatite/collagen 3D printing biological ink, adding medical-grade nano hydroxyapatite into I type collagen gel solution dissolved in acetic acid solution, and stirring to obtain the 3D printing biological ink. Correcting the skull defect three-dimensional reconstruction model confirmed in the step S1, setting printing parameters, and 3D printing a hydroxyapatite/collagen guided tissue regeneration coating on the obtained hydroxyapatite/collagen biological ink on the titanium mesh obtained by 3D printing in the step S2; the average particle size of the medical nano hydroxyapatite is 100nm, the concentration of acetic acid is 0.05mol/L, the concentration of the hydroxyapatite in the biological ink is 0.75g/100mL, and the concentration of type I collagen is 1g/100mL. The printing parameters are as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: -4 ℃, gas pressure: 200kpa, mesh diameter 0.4mm, print thickness: 3mm and the diameter of the needle of the equipment is 0.4mm.
And S4, carrying out post-treatment on the printing product prepared in the step S3, wherein the post-treatment comprises freeze drying, cross-linking, analysis technology and cobalt 60 25kGy dosage irradiation sterilization, and thus obtaining the 3D printing skull repairing titanium mesh. Specifically, the freeze-drying process conditions are as follows: pre-freezing for 12h at-60 ℃, and then drying the frozen body for 48h at the temperature of 10 ℃ and the pressure of 10 Pa; the technological conditions of glutaraldehyde steam crosslinking are as follows: crosslinking for 12 hours at the temperature of 40 ℃ and the concentration of glutaraldehyde steam of 10 percent; the thermal crosslinking process conditions are as follows: crosslinking for 48h in a vacuum drying oven at 100 ℃ and 100 Pa; the resolving process conditions are as follows: the temperature and time for the analysis were 37 ℃ and 2d in the air-drying oven.
Example 2
A preparation method of a 3D printing skull repairing titanium mesh comprises the following steps:
s1, preparing a 3D printing titanium mesh. Firstly, performing CT flat scanning and enhanced scanning on a head defect part, then performing three-dimensional reconstruction, and determining the position, size, shape and the like of the head skull defect; pouring the scanning data into software to design a bone defect model, storing the scanning data in an STL format, importing the scanning data into a 3D printer, correcting and calibrating the bone defect model by using the software, performing molding by using digital equipment according to the data of the model, and manufacturing a titanium net matched with the defect part, wherein the edge of the titanium net is 1cm higher than the edge of the defect. The chemical components of the pure titanium prosthesis accord with the GB/T13810-2017 Standard of titanium and titanium alloy processing materials for surgical implants; the 3D printing titanium net is integrated into one piece, and the edge of the titanium net is provided with 3 integrated protruding blocks, and the protruding block end is provided with a titanium nail hole. The thickness of the titanium mesh is 0.8mm, and the diameter of the mesh is 0.6mm.
S2, preparing the polydopamine microsphere modified titanium mesh. Dopamine can undergo oxidative polymerization in an alkaline (pH is more than 7.5) aerobic environment to form polydopamine nano-microspheres. Preparing a dopamine solution: dissolving 0.121g of tris (hydroxymethyl) aminomethane powder in 100mL of deionized water, titrating with dilute hydrochloric acid to adjust the pH value to 8.5, dissolving 250mg of dopamine hydrochloride powder in tris (hydroxymethyl) aminomethane solution, mixing and stirring for 80min to form dopamine solution. Adding the titanium mesh obtained or prepared in advance into a dopamine solution, carrying out magnetic stirring reaction for 24 hours at room temperature, repeatedly washing the polydopamine microsphere modified titanium mesh for 2-3 times by using pure water, and drying the polydopamine microsphere modified titanium mesh for 12 hours in a forced air drying oven at 50 ℃.
And S3, low-temperature 3D printing of a hydroxyapatite/collagen guided tissue regeneration coating. Firstly, preparing hydroxyapatite/collagen 3D printing biological ink, adding medical grade nano hydroxyapatite into I type collagen gel solution dissolved in acetic acid solution, and stirring to obtain the 3D printing biological ink. Correcting the skull defect three-dimensional reconstruction model confirmed in the step S1, setting printing parameters, and 3D printing a hydroxyapatite/collagen guided tissue regeneration coating on the obtained hydroxyapatite/collagen biological ink on the titanium mesh obtained by 3D printing in the step S2; the average particle size of the medical grade nano hydroxyapatite is 120nm, the concentration of acetic acid is 0.05mol/mL, the concentration of the hydroxyapatite in the bio-ink is 0.5g/100mL, and the concentration of type I collagen is 1.5g/100mL. The printing parameters are as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: 0 ℃, gas pressure: 100kpa, mesh diameter 0.4mm, print thickness: 2mm and the diameter of the needle of the device is 0.4mm.
And S4, post-processing the printed product prepared in the step S3, wherein the post-processing comprises freeze drying, cross-linking and analyzing processes and irradiation sterilization with cobalt 60 25kGy dosage, and the 3D printed skull repairing titanium mesh is obtained. Specifically, the freeze-drying process conditions are as follows: pre-freezing at-50 deg.C for 12h, and freeze drying at 20 deg.C under 20Pa for 48h; the technological conditions of glutaraldehyde steam crosslinking are as follows: crosslinking for 6 hours at the temperature of 40 ℃ and the concentration of glutaraldehyde steam of 20 percent; the thermal crosslinking process conditions are as follows: crosslinking for 24 hours in a vacuum drying oven at 105 ℃ and 50 Pa; the analysis process conditions are as follows: in a forced air drying oven, the analysis temperature is 50 ℃ and the analysis time is 3d.
Example 3
A preparation method of a 3D printing skull repairing titanium mesh comprises the following steps:
s1, preparing a 3D printing titanium mesh. Firstly, performing CT flat scanning and enhanced scanning on a head defect part, then performing three-dimensional reconstruction, and determining the position, size, shape and the like of the head skull defect; pouring the scanning data into software to design a bone defect model, storing the bone defect model in an STL format, importing the bone defect model into a 3D printer, correcting and calibrating the bone defect model by using the software, molding by using digital equipment according to the data of the model, and manufacturing a titanium mesh matched with the defect part, wherein the edge of the titanium mesh is 1cm higher than the edge of the defect. The chemical components of the pure titanium prosthesis accord with the standard of GB/T13810-2017 titanium and titanium alloy processing materials for surgical implants; the 3D printing titanium net is integrated into one piece, and the edge of the titanium net is provided with 3 integrated protruding blocks, and the protruding block end is provided with a titanium nail hole. The thickness of the titanium mesh is 1mm, and the diameter of the mesh is 0.6mm.
S2, preparing the polydopamine microsphere modified titanium mesh. Dopamine can undergo oxidative polymerization reaction in an alkaline (pH > 7.5) aerobic environment to form polydopamine nano-microspheres. Preparing a dopamine solution: dissolving 0.121g of tris (hydroxymethyl) aminomethane powder in 100mL of deionized water, titrating with dilute hydrochloric acid to adjust the pH to 9.0, dissolving 300mg of dopamine hydrochloride powder in tris (hydroxymethyl) aminomethane solution, mixing and stirring for 90min to form dopamine solution. And (2) adding the titanium mesh prepared in the step (S1) into a dopamine solution, magnetically stirring at room temperature for reaction for 48 hours, repeatedly washing the poly-dopamine microsphere modified titanium mesh with pure water for 2-3 times, and drying in a forced air drying oven at 40 ℃ for 24 hours.
And S3, low-temperature 3D printing of a hydroxyapatite/collagen guided tissue regeneration coating. Firstly, preparing hydroxyapatite/collagen 3D printing biological ink, adding medical-grade nano hydroxyapatite into I type collagen gel solution dissolved in acetic acid solution, and stirring to obtain the 3D printing biological ink. Correcting the skull defect three-dimensional reconstruction model confirmed in the step S1, setting printing parameters, and 3D printing a hydroxyapatite/collagen guided tissue regeneration coating on the obtained hydroxyapatite/collagen biological ink on the titanium mesh obtained by 3D printing in the step S2; the average particle size of the medical grade nano hydroxyapatite is 150nm, the concentration of acetic acid is 0.05mol/mL, the concentration of the hydroxyapatite in the bio-ink is 1g/100mL, and the concentration of type I collagen is 2g/100mL. The printing parameters are as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: 4 ℃, air pressure: 250kpa, mesh diameter 0.4mm, print thickness: 3mm, and the diameter of the needle of the equipment is 0.4mm.
And S4, post-processing the printed product prepared in the step S3, wherein the post-processing comprises freeze drying, cross-linking and analyzing processes and irradiation sterilization with cobalt 60 25kGy dosage, and the 3D printed skull repairing titanium mesh is obtained. Specifically, the freeze-drying process conditions are as follows: pre-freezing for 24h at-60 ℃, and then drying the frozen body for 48h at the temperature of 5 ℃ and the pressure of 30 Pa; the technological conditions of glutaraldehyde steam crosslinking are as follows: crosslinking for 3 hours at the temperature of 40 ℃ and under the condition of 25 percent of glutaraldehyde steam concentration; the thermal crosslinking process conditions are as follows: crosslinking for 24 hours in a vacuum drying oven under the conditions of 110 ℃ and 30 Pa; the analysis process conditions are as follows: in a forced air drying oven, the analysis temperature is 45 ℃ and the analysis time is 3d.
Example 4
A preparation method of a 3D printing skull repairing titanium mesh comprises the following steps:
s1, preparing a 3D printing titanium mesh. Firstly, performing CT flat scanning and enhanced scanning on a head defect part, then performing three-dimensional reconstruction, and determining the position, size, shape and the like of the head skull defect; pouring the scanning data into software to design a bone defect model, storing the bone defect model in an STL format, importing the bone defect model into a 3D printer, correcting and calibrating the bone defect model by using the software, molding by using digital equipment according to the data of the model, and manufacturing a titanium mesh matched with the defect part, wherein the edge of the titanium mesh is 1cm higher than the edge of the defect. The chemical components of the pure titanium prosthesis accord with the GB/T13810-2017 Standard of titanium and titanium alloy processing materials for surgical implants; 3D prints the titanium net and is integrated into one piece, and the titanium net edge sets up 3 pieces of integration protrusion pieces, and protrusion piece end is equipped with titanium nail hole. The thickness of the titanium mesh is 0.6mm, and the diameter of the mesh is 0.6mm.
S2, preparing the polydopamine microsphere modified titanium mesh. Dopamine can undergo oxidative polymerization in an alkaline (pH is more than 7.5) aerobic environment to form polydopamine nano-microspheres. Preparing a dopamine solution: dissolving 0.121g of tris (hydroxymethyl) aminomethane powder in 100mL of deionized water, titrating with dilute hydrochloric acid to adjust the pH value to 9.5, dissolving 200mg of dopamine hydrochloride powder in tris (hydroxymethyl) aminomethane solution, mixing and stirring for 60min to form dopamine solution. Adding the titanium mesh prepared in the step S1 into a dopamine solution, carrying out magnetic stirring reaction for 36 hours at room temperature, repeatedly washing the polydopamine microsphere modified titanium mesh for 2-3 times by using pure water, and drying the polydopamine microsphere modified titanium mesh for 12 hours in a forced air drying oven at 45 ℃;
and S3, low-temperature 3D printing of a hydroxyapatite/collagen guided tissue regeneration coating. Firstly, preparing hydroxyapatite/collagen 3D printing biological ink, adding medical-grade nano hydroxyapatite into I type collagen gel solution dissolved in acetic acid solution, and stirring to obtain the 3D printing biological ink. Correcting the skull defect three-dimensional reconstruction model confirmed in the step S1, setting printing parameters, and 3D printing a hydroxyapatite/collagen guided tissue regeneration coating on the obtained hydroxyapatite/collagen biological ink on the titanium mesh obtained by 3D printing in the step S2; the average particle size of the medical grade nano hydroxyapatite is 120nm, the concentration of acetic acid is 0.05mol/mL, the concentration of the hydroxyapatite in the bio-ink is 1.5g/100mL, and the concentration of type I collagen is 3g/100mL. The printing parameters are as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: 4 ℃, air pressure: 300kpa, mesh diameter 0.4mm, print thickness: 3mm and the diameter of the needle of the equipment is 0.4mm.
And S4, carrying out post-treatment on the printing product prepared in the step S3, wherein the post-treatment comprises freeze drying, cross-linking, analysis technology and cobalt 60 25kGy dosage irradiation sterilization, and thus obtaining the 3D printing skull repairing titanium mesh. Specifically, the freeze-drying process conditions are as follows: pre-freezing for 24h at-50 ℃, and then freezing and drying for 72h at 25 ℃ and 15 Pa; the technological conditions of glutaraldehyde steam crosslinking are as follows: crosslinking for 6 hours at the temperature of 40 ℃ and the concentration of glutaraldehyde steam of 20 percent; the technological conditions of the thermal crosslinking are as follows: crosslinking for 48h in a vacuum drying oven at the temperature of 110 ℃ and under the condition of 100 Pa; the analysis process conditions are as follows: in a forced air drying oven, the analysis temperature is 45 ℃ and the analysis time is 4d.
Comparative example 1
And (4) obtaining a finished product titanium mesh in the market, and cutting and shaping to obtain the skull repairing titanium mesh.
Examples of the experiments
The titanium meshes obtained in example 1 and comparative example 1 were used for a skull defect model of a New Zealand rabbit. 40 New Zealand rabbit skull defect repair models are taken for the test and divided into a control group and a test group, wherein each group comprises 20 cases. The test group is the example 1, the skull repairing titanium mesh is printed by 3D, the comparison group is the comparative example 1, the comparison group is a commercially available finished product titanium mesh, and the skull repairing titanium mesh is prepared by cutting and shaping. The test period is 3-18 months, and the conditions of complications (incisional infection, titanium net leakage, bone leakage, titanium net infection and asymmetric skull) after the skull defect repair of the New Zealand rabbits are observed. The results are shown in the following table:
the skull repairing titanium mesh prepared by the method is used for a skull defect model of a New Zealand rabbit, and complications are obviously lower than those of a control group, because the titanium mesh is prepared by a 3D printing method, the titanium mesh can be molded according to different defect conditions, the manufactured titanium mesh has high precision, no sharp edge can be formed in the molding process, the compatibility with a defect part is good, and the matching effect can be completely achieved; in addition, the surface roughness and the bioactivity of the titanium mesh material can be increased by adopting a 3D printing titanium mesh composite polydopamine microsphere and a guided tissue regeneration layer, and the risks of postoperative infection and exposure are avoided.
One or more technical solutions in the embodiments of the present invention at least have the following technical effects or advantages:
(1) The raw materials are easy to obtain, safe and environment-friendly, and hidden danger brought to human bodies in the preparation process and the use of final products is avoided;
(2) The titanium mesh is prepared by adopting a 3D printing method, the titanium mesh can be molded according to different defect conditions, the prepared titanium mesh has high precision, sharp edges cannot be formed in the molding process, the compatibility with defect parts is good, the matching effect can be completely achieved, and the risk of post-operation titanium mesh exposure is avoided;
(3) The polydopamine is mainly secreted from the foot gland of the mussel, contains a large amount of adhesive protein, is secreted into seawater, gradually coagulates, forms byssus and firmly adheres to the surface of a substrate material. The polydopamine can promote the adhesion of cells, has good biocompatibility and biodegradability, and can be rapidly developed and widely applied as a simple and universal functional surface modification method. The polydopamine not only can be used for modifying regular surfaces, but also can be used for modifying three-dimensional surfaces with higher complexity, such as metal, cardiovascular stent surfaces, carbon nanotubes and the like. After the three-dimensional surfaces are modified by polydopamine, the polydopamine has secondary reactivity, and can also be directly used for connecting biomolecules and medicaments or combined with other coating technologies to prepare multifunctional composite coatings. When the polydopamine is coated on the surface of the substrate material, the thickness can be thin, the combination is firm, and the surface of the substrate material can obtain good hydrophilicity and adhesiveness. The literature reports that the polydopamine coating can promote in-vitro osteogenic differentiation and calcium mineralization, and can promote osteogenesis and increase osseointegration in-vivo experiments. The poly-dopamine nano-microsphere modification is carried out on the titanium mesh, so that the biocompatibility and the bioactivity of the porous titanium mesh can be improved, and the secondary coating modification is carried out on the surface of the porous titanium mesh, so that the adhesion, the proliferation and the secretion of extracellular matrix of seed cells on the surface of the material are facilitated, and the rapid fusion of the repairing material and soft tissues is accelerated;
(4) Good bone conductivity, and is beneficial to the growth of new bone tissues and vascular tissues. Hydroxyapatite is the main component of inorganic salt of natural bone, has good bone conductivity and biocompatibility, is considered as an ideal material for bone defect repair, and particularly, the nano-grade hydroxyapatite is similar to the inorganic component of the natural bone, and can be introduced into the bone repair material to ensure that the material has great superiority in the aspects of mechanics and biology, thereby being beneficial to the growth of new bone tissues and vascular tissues;
(5) The type I collagen is a main structural protein of a spine animal, is extracellular matrix secreted by osteoblasts in an osteogenesis process, is a scaffold deposited by calcium salt, an accelerant of a bone matrix double layer and a template of the double layer; can promote cell migration, adsorption and differentiation and regulate cell growth, is approved by the FDA in the United states as a biological material, and has a series of collagen bone implant products. The type I collagen has the advantages of low immunogenicity, no toxic or side effect of in vivo degradation products and the like, but has poor mechanical property and high degradation rate. The nano-hydroxyapatite has good bone conductivity and biocompatibility, but the single hydroxyapatite has larger brittleness and low toughness. Therefore, the hydroxyapatite and the type I collagen are used in a compounding way, so that the obtained bone repair material has good mechanical property and controllable biodegradation time, and the skull repair material can maintain the morphological structure within a certain time or for a long time and is matched with the biomechanical property of the original skull bone tissue of the implanted part;
(6) The poly dopamine microspheres and the guide tissue regeneration layer are compounded on the titanium mesh, so that the problems of expansion with heat and contraction with cold, quick heat conduction, susceptibility to cold and heat, irritation to scalp, dura mater and surrounding skull, related complications and the like caused by the fact that the titanium mesh is only used can be solved.
(7) The pore size and porosity of micropores communicated with the bone repair material can be accurately controlled by a 3D printing method, and the method is favorable for adhesion of seed cells and growth factors and exchange of nutrient substances and metabolites. The low-temperature rapid prototyping manufacturing technology (LDM) is a novel rapid prototyping technology based on the principle of rapid prototyping technology and combined with a phase separation method, and is different from other rapid prototyping technologies in that the temperature in a prototyping cavity is controlled to be about-30 ℃, a solution extruded by a nozzle is rapidly condensed at low temperature, the nozzle moves according to a program under the control of a computer, a printing layer is finally molded into a three-dimensional porous framework through layer-by-layer superposition, the properties and the structure of a material are not damaged in the material processing process, and the LDM belongs to the range of green manufacturing.
Finally, it should be further noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. Therefore, it is intended that the appended claims be interpreted as including preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (5)
1. A preparation method of a 3D printing skull repairing titanium mesh is characterized by comprising the following steps:
analyzing the head to be repaired to obtain skull defect part information;
3D printing is carried out according to the skull defect part information to obtain a titanium mesh skull model;
adding the titanium mesh skull model into a dopamine solution to obtain a polydopamine microsphere modified titanium mesh skull model;
dissolving type I collagen in a solvent to obtain a gel solution;
mixing hydroxyapatite with the gel solution to obtain 3D printing biological ink;
printing the 3D printing biological ink on the polydopamine microsphere modified titanium mesh skull model according to the skull defect part information, and performing post-treatment to obtain a 3D printing skull repairing titanium mesh, wherein the post-treatment comprises freeze drying, crosslinking, an analytic process and irradiation sterilization;
the method for obtaining the polydopamine microsphere modified titanium mesh skull model specifically comprises the following steps:
dissolving tris (hydroxymethyl) aminomethane powder in deionized water, titrating with dilute hydrochloric acid to adjust the pH value to 7.5-10, dissolving dopamine hydrochloride powder in tris (hydroxymethyl) aminomethane solution, mixing and stirring for 30-120 min to form dopamine solution; adding the titanium mesh skull model into a dopamine solution, carrying out magnetic stirring reaction for 24-48 h at room temperature, repeatedly washing the polydopamine microsphere modified titanium mesh with pure water for 2-3 times, and drying in a forced air drying oven at 37-52 ℃ for 12-24 h to obtain the polydopamine microsphere modified titanium mesh skull model;
the thickness of the titanium mesh skull model is 0.4 mm-10 mm, and the mesh diameter of the titanium mesh skull model is 0.4 mm-0.8 mm; the mass concentration of the dopamine in the dopamine solution is 0.1-20 mg/mL; 0.5-3 g of type I collagen is contained in each 100mL of the 3D printing biological ink; every 100mL of the 3D printing biological ink contains 0.5-1.5 g of hydroxyapatite, wherein the hydroxyapatite is medical-grade nano hydroxyapatite, and the particle size of the medical-grade nano hydroxyapatite is 50-150 nm;
the freeze drying comprises a pre-freezing process and a freeze drying process, wherein the freezing temperature of the pre-freezing process is-80 ℃ to-20 ℃, the pre-freezing time of the pre-freezing process is 3h to 24h, the freezing temperature of the freeze drying process is-50 ℃ to 37 ℃, the pressure of the freeze drying process is 0.1Pa to 50Pa, and the freezing time of the freeze drying process is 24h to 72h;
the crosslinking comprises a glutaraldehyde steam crosslinking process and a heat crosslinking process, wherein the glutaraldehyde steam crosslinking is carried out in a closed container at the crosslinking temperature of 37-52 ℃, the volume concentration of glutaraldehyde steam crosslinked by glutaraldehyde steam is 5-25%, and the time for glutaraldehyde steam crosslinking is 2-12 h; the heat cross-linking is carried out in a vacuum drying oven at the temperature of 100-110 ℃ and the pressure of 10-150 Pa for 12-48 h.
2. The preparation method of the 3D printing skull repairing titanium mesh according to claim 1, wherein the solvent is an acetic acid solution, and the concentration of the acetic acid solution is 0.03mol/L-0.07mol/L.
3. The preparation method of the 3D printing skull repairing titanium mesh according to claim 1, wherein the 3D printing biological ink is printed on the titanium mesh skull model, and the printing parameters of the low-temperature 3D printing biological ink are set as follows: material deposition rate: 10mm/s, extrusion speed: 0.09mm/min, print layer thickness: 0.5mm, platform forming temperature: -4 to 10 ℃, air pressure: 5-300 kpa, mesh diameter 0.4-0.8 mm, printing thickness: 2-4 mm, and the diameter of the needle of the equipment is 0.4mm.
4. The preparation method of the 3D printing skull repairing titanium mesh according to claim 3, wherein the resolving process is that resolving temperature is 37-52 ℃ and resolving time is 2-4D in a forced air drying oven.
5. A3D printing skull repairing titanium mesh, which is characterized in that the skull repairing titanium mesh is prepared by the preparation method of the 3D printing skull repairing titanium mesh according to any one of claims 1 to 4.
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| CN115554467B (en) * | 2022-11-10 | 2024-01-30 | 奥精医疗科技股份有限公司 | Skull repairing material and preparation method thereof |
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