CN116099046A - Artificial periosteum with slow-release function and preparation method thereof - Google Patents
Artificial periosteum with slow-release function and preparation method thereof Download PDFInfo
- Publication number
- CN116099046A CN116099046A CN202310040821.7A CN202310040821A CN116099046A CN 116099046 A CN116099046 A CN 116099046A CN 202310040821 A CN202310040821 A CN 202310040821A CN 116099046 A CN116099046 A CN 116099046A
- Authority
- CN
- China
- Prior art keywords
- hydrogel
- layer
- artificial periosteum
- periosteum
- crosslinking
- 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.)
- Withdrawn
Links
- 208000006735 Periostitis Diseases 0.000 title claims abstract description 84
- 210000003460 periosteum Anatomy 0.000 title claims abstract description 84
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- 239000000126 substance Substances 0.000 claims abstract description 17
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- 238000000034 method Methods 0.000 claims description 24
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- 239000000843 powder Substances 0.000 claims description 22
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Images
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- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
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Abstract
The invention discloses an artificial periosteum with a slow release function and a preparation method thereof, wherein the artificial periosteum has a three-layer structure, and comprises a middle layer and hydrogel layer compositions positioned at two sides of the middle layer; the middle layer is a high polymer layer with a reticular structure, the hydrogel layer is a hydrogel sheet, a fixed reticular structure exists in the hydrogel sheets at two sides, and the middle layer is fixed through the crosslinking between the two hydrogel sheets; the intermediate layer has a pore structure and has fixing sites. The invention adopts a three-layer structure, the middle layer is a high polymer layer, the two sides are hydrogel layers, and the middle layer adopts a reticular high polymer layer, so that on one hand, the integral mechanical property of periosteum can be improved, and on the other hand, the high polymer layer can be used as a platform for adding medicines and bioactive substances.
Description
Technical Field
The invention belongs to the technical field of biomedical appliances, and particularly relates to an artificial periosteum with a slow-release function and a preparation method thereof.
Background
Bone defects are common diseases of orthopaedics, are usually caused by various factors such as wounds, infection, tumors and the like, and are one of the difficult problems of clinical orthopaedics treatment. Currently, a common clinical treatment is bone grafting, which fills the bone defect site with a bone repair material.
Periosteum is a compatible connective tissue membrane that coats the outside of the joint on the bone surface. This film is typically divided into superficial fibrous layers and deep germinal layers. The shallow surface layer is mainly formed by closely arranging fiber bundles, so as to play a role in protection; the hair growth layer is closely attached to the surface of bone, is arranged and transported, is rich in various bioactive factors and precursor cells responsible for osteogenesis and angiogenesis, and is also called an osteogenesis layer.
However, there are many cases of periosteal defects in clinic, and autologous periosteal transplantation and allogenic periosteal transplantation are mostly used in clinic to cope with the periosteal defects. Autologous periosteal grafting is limited in source and constitution of the patient, and overdose may cause a series of problems such as infection of the collecting site of the patient. Thus, there is an urgent need to construct suitable artificial periosteal substitutes using tissue engineering based on the characteristics of periosteal tissue.
At present, the clinical application of the artificial periosteum is less, and the existing periosteum has single structure and function and is less in release and bearing aiming at loading bioactive substances, active ions, medicines and the like. In addition, in the existing research, the periosteum is mostly made of hydrogel materials, and the materials are relatively poor in mechanical property, so that the mechanical reinforcement of the periosteum is also the focus of the research.
Disclosure of Invention
The invention mainly solves the technical problem of providing an artificial periosteum with a slow-release function and a preparation method thereof, wherein the artificial periosteum adopts a three-layer structure, a middle layer is a high polymer layer, two sides are hydrogel layers, and the middle layer adopts a reticular high polymer layer, so that on one hand, the integral mechanical property of the periosteum can be improved, and on the other hand, the high polymer layer can be used as a platform for adding medicines and bioactive substances. Namely, the artificial periosteum has the advantages of excellent mechanical property, good interface bonding strength and good biocompatibility, overcomes the defect of single function of the existing artificial periosteum, and solves the problems in the prior art.
In order to solve the technical problems, the invention adopts a technical scheme that: the invention provides an artificial periosteum with a slow release function, which has a three-layer structure and comprises a middle layer and hydrogel layer layers positioned on two sides of the middle layer; the middle layer is a high polymer layer with a reticular structure, the hydrogel layer is a hydrogel sheet, a fixed reticular structure exists in the hydrogel sheets at two sides, and the middle layer is fixed through the crosslinking between the two hydrogel sheets;
the intermediate layer has a pore structure and has fixing sites.
Further, the porosity of the intermediate layer is 10% -98%; the pore size of the intermediate layer is 100-1000 μm.
Further, the fixing sites are circular, rectangular or polygonal in shape, and each fixing site has an area of 9mm 2 -40mm 2 The number of fixing sites is 4-12.
Further, the thickness of the artificial periosteum is 1mm-5mm; the thickness of the intermediate layer is 100-2000 mu m; the hydrogel layer has a thickness of 400 μm to 1500 μm.
Further, the middle layer is rectangular, and the area of the hydrogel layer is larger than that of the middle layer and completely wraps the middle layer.
The side length of the hydrogel layer of the artificial periosteum is 3mm-5mm longer than the length of the middle high polymer layer.
Further, the thickness of the fixed net structure is 0.2mm-0.5mm, the shape of the holes on the fixed net structure is rectangular, and the area of the holes is 25mm 2 -300mm 2 。
Further, the artificial periosteum is a soft tissue repair membrane, and the rectangular length of the artificial periosteum is 10mm-40mm; or when the artificial periosteum is applied to a large-area bone repair part, the rectangular length of the artificial periosteum is 50-100 mm.
Further, the intermediate layer is formed by a 3D printing forming technology or a flat plate die method.
The invention also provides a preparation method of the artificial periosteum with the slow release function according to claim 1, which comprises the following steps:
step 1: the preparation of the middle layer comprises mixing bioactive substances or medicines with organic materials, and shaping the powder into porous net-shaped or sheet-shaped bracket with stable space structure;
step 2: preparation of a fixed mesh structure:
the method comprises the steps of adopting a Fused Deposition (FDM) printing method to prepare PCL wires as raw materials; for example, the thickness of the printing layer is 0.05mm, the printing height is 0.2mm, and the size is 35mm by 0.2mm;
step 3: preparation of hydrogel layer comprises mixing sodium alginate with
Mixing calcium sulfate and strengthening powder, adding an aqueous solution to prepare a mixed strengthening sodium alginate solution, then placing the fixed net structure prepared in the step 2 into a template, adding the evenly stirred strengthening sodium alginate solution into the template for low-temperature preservation, and drying hydrogel after the heat preservation is finished to obtain a hydrogel sheet; then placing the prepared hydrogel sheet into a crosslinking solution for crosslinking, taking out the hydrogel sheet, and then using a modified crosslinking solution for crosslinking to finally obtain a single-layer hydrogel sheet;
step 4: periosteum molding: the step totally requires an upper hydrogel sheet and a lower hydrogel sheet prepared in the step 3; placing the hydrogel sheet prepared in the step 3 into a mould after being treated by EDTA solution; placing the intermediate layer prepared in the step 1 on the hydrogel sheet, and then placing another hydrogel sheet prepared in the step 3 on the uppermost surface; and extruding the artificial periosteum by using a flat plate, and finally placing the artificial periosteum into a crosslinking solution for crosslinking to obtain the required artificial periosteum.
Further, the bioactive substances in the step 1 comprise one or more of bioceramics, metal salts, metal oxides and bioactive glass;
the medicine in the step 1 is one or more of antibacterial medicine, antitumor medicine and medicine for treating osteoporosis.
Further, in the step 1, the addition amount of the bioactive substances is 0.5% -20% of the total mass, the addition amount of the medicines is 0.1-2% of the total mass, and the rest components are organic materials.
Further, the bioceramics include one or more of tricalcium phosphate, hydroxyapatite, calcium silicate, calcium sulfate, octacalcium phosphate, and akenite.
Further, the metal salt includes one or more of magnesium chloride, magnesium sulfate, magnesium nitrate, zinc chloride, zinc sulfate, zinc nitrate, lithium chloride, copper sulfate, silver chloride, and iron chloride.
Further, the metal oxide includes one or more of magnesium oxide, zinc oxide, lithium oxide, silicon dioxide, copper oxide, and calcium oxide.
Further, the bioactive glass is bioactive glass based on silicon dioxide, phosphorus pentoxide or calcium oxide and bioactive glass with one or more of Li, B, mg, zn, cu, co and Ga added on the basis.
Further, the organic material in the step 1 includes one or more of Polycaprolactone (PCL), polylactic acid (PLA), polylactic acid-glycolic acid copolymer (PLGA), chitosan, gelatin, hyaluronic acid and silk fibroin.
Further, the mixing of the bioactive substances or/and the medicines with the organic materials in the step 1 includes directly mixing the powder, preparing the powder into a wire after mixing the powder, and dissolving the powder in a solvent by adopting a solvent method.
Further, the pore shape of the intermediate layer in the step 1 includes one or more of rectangular, circular, and space network structures.
Further, the strengthening powder in the step 3 comprises one or more of strontium chloride, magnesium chloride, zinc sulfate, magnesium sulfate and strontium sulfate, and the adding amount of the strengthening powder is 0.5-20% wt.
In step 3, the hydrogel prepared from the reinforced sodium alginate solution is crosslinked and dried for a plurality of times, and the operation steps are that the hydrogel is dried and then crosslinked, and the steps can be repeated for a plurality of times.
Further, in the step 3, the modified crosslinking solution is a mixed solution of a plurality of ions, including one or more of barium chloride, aluminum chloride and ferric chloride, and the concentration of metal cations in the mixed solution is 0.1 mol/L-0.5 mol/L.
Further, in the step 3, the addition amount of the sodium alginate and the calcium sulfate is 10% -20% of the ratio of Ca ions to carboxyl ions in the sodium alginate.
Further, in the step 3, the strengthening powder is 0.5% -5% of the total mass of the sodium alginate and the calcium sulfate.
Further, in the step 3, the concentration of sodium alginate in the reinforced sodium alginate solution is 1.5% -5%.
Further, in the step 3, the crosslinking solution includes one or more of strontium chloride, calcium chloride, magnesium chloride and zinc chloride.
Further, in the step 3, the concentration of chloride ions of the crosslinking solution is 0.1mol/L to 1 mol/L.
Further, in the step 3, one or more of barium chloride, aluminum chloride and ferric chloride are included in the modified crosslinking solution.
Further, in the step 3, the concentration of chloride ions of the modified crosslinking solution is 0.1mol/L to 0.5 mol/L.
Further, in the step 3, the template is placed into a template for low-temperature preservation after being uniformly stirred, and the thickness of the template is 2mm-4mm;
in the step 3, the conditions for low-temperature preservation are as follows: preserving for 12-24 hours at the temperature of 4-6 ℃;
in the step 3, the drying conditions are as follows: and (3) placing the solidified hydrogel sheet into a drying box, and drying for 2-4 days at the temperature of 25-35 ℃ to obtain the hydrogel sheet.
Further, in the step 4, the two hydrogel sheets are bonded by pressing and then crosslinking;
the crosslinking time is 12-24 h, and the concentration of the crosslinking solution is 0.1mol/L-1mol/;
in the step 4, the pressure in the extrusion process is 5kPa-10kPa, and the extrusion time is 6-12 hours.
Further, the crosslinking solution in the step 4 is a solution composed of one or more of calcium chloride, magnesium chloride, zinc chloride and strontium chloride.
The artificial periosteum prepared by the preparation method of the artificial periosteum has excellent mechanical properties. The artificial periosteum prepared by the invention can also be loaded with bioactive substances, medicines and antibacterial substances, so that the actual application effect of the artificial periosteum is greatly improved.
The invention provides a preparation method of a multifunctional artificial periosteum, which is characterized in that the main body of the preparation method is a hydrogel structure, and a high polymer in the middle layer is used as a modified platform to release active substances and medicines. The polymer adopts degradable materials, the degradation application is controllable, and the release of bioactive substances and medicines can be controlled while the degradation is carried out, so that the polymer plays a long-term role. And the existence of the polymer can integrally improve the mechanical property of the artificial periosteum.
The artificial periosteum prepared by the multifunctional bionic artificial periosteum preparation method can be applied to cartilage tissue defect and bone-cartilage integrated repair.
The beneficial effects of the invention are as follows:
(1) The artificial periosteum adopts a three-layer structure, the middle layer is a high polymer layer, the two sides of the middle layer are hydrogel layers, and the middle layer adopts a net-shaped high polymer layer, so that on one hand, the integral mechanical property of the periosteum can be improved, and on the other hand, the high polymer layer can be used as a platform for adding medicines and bioactive substances. In the preparation of the porous polymer scaffold, it is convenient to add modified substances and drugs thereto without damaging the additives.
(2) The hydrogel layer materials are arranged on the two sides of the periosteum, so that the surface characteristics of the natural periosteum can be imitated, and trace bioactive substances can be added in the preparation process of the hydrogel, so that the bioactivity of the material is improved.
(3) According to the invention, the artificial periosteum is prepared by adopting a three-layer structure, the hydrogel layer is modified by adding ceramic powder, and the sodium alginate hydrogel is crosslinked for multiple times, so that the obtained hydrogel has a good bonding effect, and in addition, the ceramic powder added into the hydrogel also plays a role in increasing the mechanical property of the hydrogel and accelerating the crosslinking.
(4) The middle high polymer layer can be formed by 3D printing, and the 3D printing technology can be fully utilized to prepare the middle layer with a complex shape, for example, the 3D printing reticular middle layer, so that the surface area is small, and the bonding effect of two hydrogel layers is improved.
The foregoing description is only an overview of the present invention, and is intended to provide a better understanding of the present invention, as it is embodied in the following description, with reference to the preferred embodiments of the present invention and the accompanying drawings.
Drawings
FIG. 1 is a schematic view (cross-sectional view) of a three-layer structure of the present invention;
FIG. 2 is a schematic illustration of the anchoring network inside the hydrogel layer of the present invention;
FIG. 3 is a schematic view of the structure of the hydrogel layer of the present invention;
FIG. 4 is a three-dimensional model of an intermediate layer of the present invention (molded using 3D printing techniques);
FIG. 5 is a schematic illustration of another construction of an intermediate layer of the present invention (formed using a flat die method).
Detailed Description
The following specific embodiments of the invention are described in order to provide those skilled in the art with an understanding of the present disclosure. The invention may be embodied in other different forms, i.e., modified and changed without departing from the scope of the invention.
Example 1: an artificial periosteum with a slow release function, as shown in fig. 1 to 5, has a three-layer structure, comprising an intermediate layer 200 and hydrogel layers 100 positioned at both sides of the intermediate layer; the middle layer is a high polymer layer with a reticular structure, the hydrogel layer is a hydrogel sheet, a fixed reticular structure 110 exists in the hydrogel sheets at two sides, and the middle layer is fixed through the crosslinking between the two hydrogel sheets;
the intermediate layer has a pore structure and has fixing sites.
The intermediate layer is formed by using a 3D printing technology, and may be a perforated plate (fig. 5), which is also a mesh structure in this embodiment, and there may be adjustable fixing sites 210 on the plate, or a porous three-dimensional mesh structure (fig. 4). In terms of materials, the hydrogel layer may incorporate bioactive substances, drugs, or metal ions to improve its bioactivity or ability to bind to bone. In addition, the middle layer material is made of high polymer materials, and is characterized in that biodegradation can be realized, and slow release of medicines or ions can be realized in the degradation process.
The porosity of the intermediate layer is 10% -98%; the pore size of the intermediate layer is 100-1000 μm.
The shape of the fixing sites is round, rectangular or polygonal, and the area of each fixing site is 9mm 2 -40mm 2 The number of fixing sites is 4-12.
The thickness of the artificial periosteum is 1mm-5mm; the thickness of the intermediate layer is 100-2000 mu m; the hydrogel layer has a thickness of 400 μm to 1500 μm.
The middle layer is rectangular, and the area of the hydrogel layer is larger than that of the middle layer and completely wraps the middle layer.
The side length of the hydrogel layer of the artificial periosteum is 3mm-5mm longer than the length of the middle high polymer layer.
The thickness of the fixed net structure is 0.2mm-0.5mmThe shape of the pore on the fixed net structure is rectangle, and the area of the pore is 25mm 2 -300mm 2 。
The artificial periosteum is a soft tissue repair membrane, and the rectangular length of the artificial periosteum is 10mm-40mm; or when the artificial periosteum is applied to a large-area bone repair part, the rectangular length of the artificial periosteum is 50-100 mm.
The embodiment also provides a preparation method of the artificial periosteum with the slow release function, which comprises the following steps:
step 1: the preparation of the middle layer comprises mixing bioactive substances or medicines with organic materials, forming by 3D printing forming technology or flat plate mold method, and forming powder into porous net-shaped or sheet-shaped bracket with stable space structure;
step 2: preparation of a fixed mesh structure:
the method comprises the steps of adopting a Fused Deposition (FDM) printing method to prepare PCL wires as raw materials;
step 3: preparing a hydrogel layer, namely mixing sodium alginate, calcium sulfate and strengthening powder, adding an aqueous solution to prepare a mixed strengthening sodium alginate solution, then placing the fixed net structure prepared in the step 2 into a template, adding the evenly stirred strengthening sodium alginate solution into the template for low-temperature preservation, and drying hydrogel after the heat preservation is finished to obtain a hydrogel sheet; then placing the prepared hydrogel sheet into a crosslinking solution for crosslinking, taking out the hydrogel sheet, and then using a modified crosslinking solution for crosslinking to finally obtain a single-layer hydrogel sheet;
step 4: periosteum molding: the step totally requires an upper hydrogel sheet and a lower hydrogel sheet prepared in the step 3; placing the hydrogel sheet prepared in the step 3 into a mould after being treated by EDTA solution; placing the intermediate layer prepared in the step 1 on the hydrogel sheet, and then placing another hydrogel sheet prepared in the step 3 on the uppermost surface; and extruding the artificial periosteum by using a flat plate, and finally placing the artificial periosteum into a crosslinking solution for crosslinking to obtain the required artificial periosteum.
The following are specific examples:
example 1 a method for preparing an artificial periosteum with bioactivity and antibacterial activity:
the preparation method of the bioactive antibacterial artificial periosteum is realized by the following steps:
step 1: and preparing a periosteum intermediate layer. Uniformly mixing 2g of tricalcium phosphate, 20g of polycaprolactone and 0.5g of zinc chloride powder, preparing the mixture into a wire, and then adopting an FDM printing (one of 3D printing) technology to prepare the porous reticular stent, wherein the porosity of the stent is 90%, and the thickness is 1.5mm.
Step 2: preparation of a fixed mesh structure:
the PCL fiber is used as a raw material, the thickness of a printing layer is 0.05mm, the printing height is 0.2mm, and the size is 35mm by 0.2mm;
step 3: and (3) preparing a hydrogel layer. And (3) mixing sodium alginate, calcium sulfate and strengthening powder, adding water to prepare a hydrogel solution, placing the fixed net structure prepared in the step (2) into a template, and adding the evenly stirred strengthening sodium alginate solution into the template to be paved, wherein the height of the template is 3mm. And (3) preserving the template filled with the hydrogel at the temperature of 5 ℃ for 24 hours, and drying the sample piece by using a drying box after the heat preservation is finished, wherein the drying temperature is 30 ℃, and the drying time is 48 hours. And drying to obtain the hydrogel sheet. The hydrogel sheet was placed in a mixed solution of barium chloride, ferric chloride and zinc chloride and soaked for 24 hours to fully crosslink. And (3) after the crosslinking is finished, the hydrogel is crosslinked again by using a reinforced crosslinking solution, wherein the crosslinking solution is a mixed solution of barium chloride, ferric chloride and zinc chloride, the crosslinking time is 48 hours, and the monolayer hydrogel is obtained after the crosslinking is finished.
Step 4: preparation of artificial periosteum. The single-layer hydrogel obtained in step 3 was placed in a mold after the surface was treated with EDTA solution, and then the mesh-shaped scaffold prepared in step 1 was placed on the hydrogel of the template after the treatment with EDTA solution, followed by the second hydrogel layer on top Fang Fangzhi. Then pressing on hydrogel, and then crosslinking by using calcium chloride crosslinking solution to obtain the artificial periosteum.
Example 2 a method for preparing an artificial periosteum with drug release:
step 1: preparation of periosteum intermediate layer. Polylactic acid and strontium ranelate are mixed to prepare a wire material, and the wire material is prepared into a porous reticular stent by using the FDM technology, wherein the thickness of the reticular stent is 1mm.
Step 2: preparation of a fixed mesh structure:
the PCL fiber is used as a raw material, the thickness of a printing layer is 0.05mm, the printing height is 0.2mm, and the size is 35mm by 0.2mm;
step 3: preparation of the hydrogel layer. Mixing sodium alginate, calcium sulfate and strontium ranelate powder, adding water to prepare hydrogel solution, placing the fixed net structure prepared in the step 2 into a template, and adding the uniformly stirred reinforced sodium alginate solution into the template to be paved, wherein the height of the template is 3mm. And (3) preserving the template filled with the hydrogel at the temperature of 5 ℃ for 24 hours, and drying the sample piece by using a drying box after the heat preservation is finished, wherein the drying temperature is 30 ℃, and the drying time is 48 hours. And drying to obtain the hydrogel sheet. The hydrogel sheet is placed into a mixed solution of calcium chloride and strontium chloride to be soaked for 24 hours, and is fully crosslinked. And (3) after the crosslinking is finished, the hydrogel is crosslinked again by using a reinforced crosslinking solution, wherein the crosslinking solution is a mixed solution of barium chloride, ferric chloride and zinc chloride, the crosslinking time is 48 hours, and the monolayer hydrogel is obtained after the crosslinking is finished.
Step 4: preparation of artificial periosteum. Preparing two hydrogel layers according to the step 3, respectively soaking the two hydrogel layers by using EDTA solution, then placing the polymer mesh stent prepared in the step 1 on the hydrogel layers when the hydrogel layers are placed in a template, then placing another hydrogel sheet above the hydrogel layers, pressing the hydrogel sheets, and then soaking the hydrogel sheets by using a crosslinking solution to obtain the required slow-release strontium ranelate periosteum.
The artificial periosteum prepared based on the embodiment can realize the sustained release of medicines and ions under experimental conditions, can release the medicines and ions in a targeted way aiming at the bone repair process, and accelerates the regeneration of bone tissues.
Example 3 preparation method of Artificial periosteum with multiple sustained Release function
In this example, the ability of the intermediate layer to carry biologically active substances and drugs is altered by changing the shape of the intermediate layer. The periosteum is prepared by the following steps:
step 1: and (3) preparation of an intermediate layer. Uniformly mixing 2g of tricalcium phosphate, 20g of polycaprolactone, 0.5g of strontium ranelate and 0.5g of zinc chloride powder, then adding a polyvinyl alcohol solution and a photoinitiator, uniformly stirring to prepare slurry, adopting photo-curing 3D printing, preparing the middle layer into a flat plate, and fixing a fixing site on the flat plate for fixing the hydrogel layer. The three-dimensional shape of the platform layer is shown in fig. 5.
Step 2: preparation of a fixed mesh structure:
the PCL fiber is used as a raw material, the thickness of a printing layer is 0.05mm, the printing height is 0.2mm, and the size is 35mm by 0.2mm;
step 3: preparation of the hydrogel layer: mixing sodium alginate, calcium sulfate and strontium ranelate powder, adding water to prepare hydrogel solution, placing the net structure prepared in the step 2 into a template, adding the uniformly stirred reinforced sodium alginate solution into the template, and paving, wherein the height of the template is 3mm. And (3) preserving the template filled with the hydrogel at the temperature of 5 ℃ for 24 hours, and drying the sample piece by using a drying box after the heat preservation is finished, wherein the drying temperature is 30 ℃, and the drying time is 48 hours. And drying to obtain the hydrogel sheet. The hydrogel sheet was placed in a mixed solution of calcium chloride and strontium chloride and soaked for 24 hours to fully crosslink. And (3) after the crosslinking is finished, the hydrogel is crosslinked again by using a reinforced crosslinking solution, wherein the crosslinking solution is a mixed solution of barium chloride, ferric chloride and zinc chloride, the crosslinking time is 48 hours, and the monolayer hydrogel is obtained after the crosslinking is finished.
Step 4: and (5) periosteum molding. Preparing two hydrogel layers according to the step 3, respectively soaking the two hydrogel layers by using EDTA solution, then placing the polymer mesh stent prepared in the step 1 on the hydrogel layers when the hydrogel layers are placed in a template, then placing another hydrogel sheet above the hydrogel layers, pressing the hydrogel sheets, and then soaking the hydrogel sheets by using a crosslinking solution to obtain the required slow-release strontium ranelate periosteum.
The foregoing description is only illustrative of the present invention and is not intended to limit the scope of the invention, and all equivalent structures made by the description of the invention and the accompanying drawings, or direct or indirect application in other related technical fields, are included in the scope of the invention.
Claims (10)
1. An artificial periosteum with a slow release function is characterized in that: the artificial periosteum has a three-layer structure, and comprises a middle layer and hydrogel layer layers positioned on two sides of the middle layer; the middle layer is a high polymer layer with a reticular structure, the hydrogel layer is a hydrogel sheet, a fixed reticular structure exists in the hydrogel sheets at two sides, and the middle layer is fixed through the crosslinking between the two hydrogel sheets;
the intermediate layer has a pore structure and has fixing sites.
2. The artificial periosteum with slow release function according to claim 1, wherein: the porosity of the intermediate layer is 10% -98%; the pore size of the intermediate layer is 100-1000 μm.
3. The artificial periosteum with slow release function according to claim 1, wherein: the shape of the fixing sites is round, rectangular or polygonal, and the area of each fixing site is 9mm 2 -40mm 2 The number of fixing sites is 4-12.
4. The artificial periosteum with slow release function according to claim 1, wherein: the thickness of the artificial periosteum is 1mm-5mm; the thickness of the intermediate layer is 100-2000 mu m; the hydrogel layer has a thickness of 400 μm to 1500 μm.
5. The artificial periosteum with slow release function according to claim 1, wherein: the middle layer is rectangular, and the area of the hydrogel layer is larger than that of the middle layer and completely wraps the middle layer.
The side length of the hydrogel layer of the artificial periosteum is 3mm-5mm longer than the length of the middle high polymer layer.
6. A method for preparing an artificial periosteum with a slow release function according to claim 1, which is characterized in that: the method comprises the following steps:
step 1: the preparation of the middle layer comprises mixing bioactive substances or medicines with organic materials, and shaping the powder into porous net-shaped or sheet-shaped bracket with stable space structure;
step 2: preparation of a fixed mesh structure:
the PCL fiber is prepared by adopting a fused deposition printing method, and PCL wires are used as raw materials;
step 3: preparing a hydrogel layer, namely mixing sodium alginate, calcium sulfate and strengthening powder, adding an aqueous solution to prepare a mixed strengthening sodium alginate solution, then placing the fixed net structure prepared in the step 2 into a template, adding the evenly stirred strengthening sodium alginate solution into the template for low-temperature preservation, and drying hydrogel after the heat preservation is finished to obtain a hydrogel sheet; then placing the prepared hydrogel sheet into a crosslinking solution for crosslinking, taking out the hydrogel sheet, and then using a modified crosslinking solution for crosslinking to finally obtain a single-layer hydrogel sheet;
step 4: periosteum molding: the step totally requires an upper hydrogel sheet and a lower hydrogel sheet prepared in the step 3; placing the hydrogel sheet prepared in the step 3 into a mould after being treated by EDTA solution; placing the intermediate layer prepared in the step 1 on the hydrogel sheet, and then placing another hydrogel sheet prepared in the step 3 on the uppermost surface; and extruding the artificial periosteum by using a flat plate, and finally placing the artificial periosteum into a crosslinking solution for crosslinking to obtain the required artificial periosteum.
7. The method for preparing the artificial periosteum with the slow release function according to claim 6, wherein the method comprises the following steps: the bioactive substances in the step 1 comprise one or more of bioceramics, metal salts, metal oxides and bioactive glass;
the medicine in the step 1 is one or more of antibacterial medicine, antitumor medicine and medicine for treating osteoporosis.
8. The method for preparing the artificial periosteum with the slow release function according to claim 1, wherein the method comprises the following steps: the strengthening powder in the step 3 comprises one or more of strontium chloride, magnesium chloride, zinc sulfate, magnesium sulfate and strontium sulfate, and the adding amount of the strengthening powder is 0.5-20 wt%.
9. The method for preparing the artificial periosteum with the slow release function according to claim 1, wherein the method comprises the following steps:
in the step 3, the template is placed into the template for low-temperature preservation after being uniformly stirred, and the thickness of the template is 2mm-4mm;
in the step 3, the conditions for low-temperature preservation are as follows: preserving for 12-24 hours at the temperature of 4-6 ℃;
in the step 3, the drying conditions are as follows: and (3) placing the solidified hydrogel sheet into a drying box, and drying for 2-4 days at the temperature of 25-35 ℃ to obtain the hydrogel sheet.
10. The method for preparing the artificial periosteum with the slow release function according to claim 1, wherein the method comprises the following steps: in the step 4, the bonding of the two hydrogel sheets is realized by pressing and then crosslinking;
the crosslinking time is 12-24 hours, and the concentration of the crosslinking solution is 0.1mol/L-1mol/;
in the step 4, the pressure in the extrusion process is 5kPa-10kPa, and the extrusion time is 6-12 hours.
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