CN113730041A - Double-layer guide bone regeneration support and preparation method thereof - Google Patents
Double-layer guide bone regeneration support and preparation method thereof Download PDFInfo
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- CN113730041A CN113730041A CN202010475331.6A CN202010475331A CN113730041A CN 113730041 A CN113730041 A CN 113730041A CN 202010475331 A CN202010475331 A CN 202010475331A CN 113730041 A CN113730041 A CN 113730041A
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Abstract
The invention provides a double-layer bone regeneration guiding scaffold and a preparation method thereof. The double-layer guide bone regeneration support comprises a loose layer and a compact layer, wherein the compact layer is arranged on the loose layer, the porosity of the loose layer is 92% -98%, and the porosity of the compact layer is 40% -60%. The preparation method comprises the following steps: 1) preparing and obtaining the loose layer by adopting a near-field direct-writing printing method; 2) and (2) taking the loose layer obtained in the step 1) as a receiving device, and preparing the compact layer by using an electrostatic spinning method. The loose layer is prepared by a near-field direct-writing printing method, cell adhesion, interaction between cells and the scaffold and bone tissue ingrowth are facilitated, the compact layer is prepared by an electrostatic spinning method and is beneficial to blocking epithelial and connective tissue ingrowth, and the double-layer guided bone regeneration scaffold prepared by the method has a physical barrier function and a guided bone regeneration function.
Description
Technical Field
The invention belongs to the technical field of bone repair scaffolds, and particularly relates to a double-layer bone regeneration guiding scaffold and a preparation method thereof.
Background
Bone defects caused by trauma, tumors, inflammation, congenital diseases and the like are very common in clinic, and the physical and mental health and the life quality of patients are seriously affected by the tissue damage and the dysfunction caused by the bone defects. At present, the treatment is mainly carried out clinically by methods of implanting autogenous bone, allogeneic bone, artificial bone repair materials and the like. Allogeneic bone is likely to cause immune rejection in vivo; the autogenous bone has the limitations of limited source, secondary trauma and the like. With the rapid development of tissue engineering technology, bone repair by applying the principle of tissue engineering has become a research hotspot at present. Among them, Guided Bone Regeneration (GBR) technology is one of the most common and effective methods. The key point of the technology is that the soft tissue is physically separated from the bone defect area through a mechanical barrier membrane (GBR membrane), a relatively stable bone regeneration microenvironment is created for the bone defect area, osteogenic precursor cells which grow and migrate slowly are protected from entering the bone defect area, fibrous connective tissues which grow and migrate rapidly are prevented from growing into the defect area, and the reparative regeneration of bone in the defect area is promoted.
Conventional GBR membranes can be classified into two types, i.e., absorbable membranes and non-absorbable membranes, according to their biodegradability. The non-absorbable membrane needs to be taken out through a secondary operation, so that the pain and infection risk of a patient are increased, and the clinical application of the non-absorbable membrane is limited. Currently, the most widely used absorbable barrier membrane in clinical practice is the Bio-Gide collagen membrane manufactured by Geistlich, Switzerland. The collagen is the organic component with the largest content in natural bones, has good biocompatibility and tissue repair effect, and is an ideal raw material for preparing the guided bone regeneration membrane. However, collagen membranes also have some disadvantages, such as complicated purification process and high cost; the wet mechanical strength is not good enough, and the bone regeneration space in the later period of repair is difficult to maintain because the bone is easy to collapse and shift when the bone regeneration device is used alone; the degradation speed in vivo is too fast; the single collagen material has insufficient bioactivity and osteogenic inductivity, lacks antibacterial ability, and the like. Therefore, the development of ideal bone regeneration-inducing materials has become a current research hotspot.
The common tissue engineering techniques for preparing the guided bone regeneration membrane at present are electrostatic spinning, casting molding and the like. The membrane prepared by casting molding has compact structure and can play a good role in preventing connective tissue from growing in, but the homogeneous and compact structure is not beneficial to the diffusion of nutrient substances and the adhesion and growth of cells, thereby influencing the bone regeneration and repair effect. Although the electrostatic spinning method can prepare the nano-scale fiber simulating the extracellular matrix, the method cannot prepare a three-dimensional support structure and cannot accurately control the support structure. In addition, the pores between electrospun fibers are small (on the order of tens of microns), and the fibers are densely arranged, limiting three-dimensional cell ingrowth and interaction between cells and the scaffold.
Disclosure of Invention
In view of the above-mentioned shortcomings of the prior art, the present invention provides a double-layer guided bone regeneration scaffold and a method for preparing the same, wherein the double-layer guided bone regeneration scaffold comprises a loose layer and a dense layer, the loose layer is prepared by a near-field direct writing printing method, and is beneficial to cell adhesion, interaction between cells and the scaffold, and bone tissue ingrowth, the dense layer is prepared by an electrostatic spinning method, and is beneficial to blocking epithelial and connective tissue ingrowth, and the double-layer guided bone regeneration scaffold prepared by the above method has both physical barrier function and guided bone regeneration function.
In order to achieve the above and other related objects, a first aspect of the present invention provides a double-layered guided bone regeneration scaffold, comprising a porous layer and a dense layer, wherein the dense layer is disposed on the porous layer, the porosity of the porous layer is 92% to 98%, and the porosity of the dense layer is 40% to 60%.
The porosity of the porous layer refers to the percentage of the pore volume of the porous layer to the total volume of the porous layer in a natural state. The porosity of the dense layer refers to the percentage of the pore volume of the dense layer to the total volume of the dense layer in its natural state.
Preferably, at least one of the following technical characteristics is also included:
1) the thickness ratio of the loose layer to the compact layer is 2: 1-5: 1;
2) the loose layer has a regular structure;
3) the loose layer is obtained by a near-field direct-writing printing method;
4) the compact layer is composed of fibers with random arrangement directions;
5) the compact layer is obtained by an electrostatic spinning method;
6) the loose layer and the compact layer are made of high polymer materials mixed with bone promoting components and/or antibacterial active components.
More preferably, in the characteristic 2), the loosening layer comprises a plurality of first loosening elements and second loosening elements which are alternately arranged, the first loosening elements comprise a plurality of parallel first bracket units, the second loosening elements comprise a plurality of parallel second bracket units, and the first bracket units and the second bracket units are crossed to form micropores.
Further more preferably, at least one of the following technical features is included:
a1) the first support units of different first loosening components are arranged in parallel;
a2) the second bracket units of different second loosening components are arranged in parallel;
a3) the distance between adjacent first support units in the same first loosening component is 50-800 mu m; the distance between adjacent second bracket units in the same second loose part is 50-800 mu m;
a4) the first support unit is cylindrical and has the diameter of 10-100 mu m; the second bracket unit is cylindrical and has the diameter of 10-100 mu m;
a5) the angle alpha of the intersection of the first bracket unit and the second bracket unit in the adjacent first loosening member and the second loosening member is more than 0 degrees and less than 180 degrees.
More preferably, at least one of the following technical characteristics is also included:
41) in the feature 4), the diameter of the fiber is 100nm to 1500 nm;
61) in the characteristic 6), the polymer material is a synthetic polymer material and/or a natural polymer material; the synthetic high polymer material is selected from at least one of polycaprolactone, a polycaprolactone modified material, a polylactic acid-glycolic acid copolymer modified material, polylactic acid, a polylactic acid modified material, polyglycolic acid and a polyglycolic acid modified material, and the natural high polymer material is selected from at least one of alginate, gelatin, matrigel, collagen, chitosan, fibrin and the modified materials;
62) the polymer material is characterized in that in the characteristic 6), the weight part of the polymer material is 5-20;
63) the characteristic 6) is that the osteogenesis promoting component is selected from one or more of hydroxyapatite, beta-tricalcium phosphate, bioactive glass, mesoporous silicon and graphene;
64) the bone formation promoting component is characterized in that 2-5 parts by weight of the bone formation promoting component is added;
65) in the characteristic 6), the antibacterial active component is selected from one or more of copper, zinc, magnesium, antibacterial peptide and antibiotics;
66) the antibacterial active ingredient is 0.1-1 part by weight in the characteristic 6).
The second aspect of the present invention provides a method for preparing the above double-layer guided bone regeneration scaffold, comprising the following steps:
1) preparing and obtaining the loose layer by adopting a near-field direct-writing printing method;
2) and (2) taking the loose layer obtained in the step 1) as a receiving device, and preparing the compact layer by using an electrostatic spinning method.
Preferably, the printed material of step 1) and the electrospun material of step 2) are prepared after being heated and melted or dissolved by a solvent.
More preferably, at least one of the following technical characteristics is also included:
1) the printing material of the step 1) and the electrostatic spinning material of the step 2) are high molecular materials mixed with components contributing to bone and/or antibacterial active components;
2) the solvent is selected from one or more of water, trichloromethane, dichloromethane, tetrahydrofuran, hexafluoroisopropanol, acetone and dimethyl sulfoxide;
3) the mass ratio of the solvent to the printing material of the step 1) and the electrostatic spinning material of the step 2) is 74: 26-92.9: 7.1.
still more preferably, the feature 1) further includes at least one of the following technical features:
11) the high polymer material is a synthetic high polymer material and/or a natural high polymer material; the synthetic high polymer material is selected from at least one of polycaprolactone, a polycaprolactone modified material, a polylactic acid-glycolic acid copolymer modified material, polylactic acid, a polylactic acid modified material, polyglycolic acid and a polyglycolic acid modified material, and the natural high polymer material is selected from at least one of alginate, gelatin, matrigel, collagen, chitosan, fibrin and the modified materials;
12) the weight part of the high polymer material is 5-20;
13) the osteogenesis promoting component is selected from one or more of hydroxyapatite, beta-tricalcium phosphate, bioactive glass, mesoporous silicon and graphene;
14) the bone promoting component accounts for 2-5 parts by weight;
15) the antibacterial active component is selected from one or more of copper, zinc, magnesium, antibacterial peptide and antibiotics;
16) the weight part of the antibacterial active component is 0.1-1.
Preferably, at least one of the following technical features is also included:
1) in the step 1), the printing temperature is 50-400 ℃;
2) in the step 1), one printing needle head from G23 to G30 is selected;
3) in the step 1), the air pressure of a material cylinder of the printing material is 500 kPa-2000 kPa;
4) in the step 1), the voltage of the high-voltage module is minus 50kV to plus 50 kV;
5) in the step 1), the distance between the printing needle head and the receiving plate is 1-5 mm;
6) in the step 1), the moving speed of the printing nozzle is 20-200 mm/s;
7) in the step 1), the diameter of the printing wire drawing is 10-100 μm;
8) in the step 1), the fiber interweaving angle is more than 0 degree and less than 180 degrees;
9) in the step 1), the fiber spacing is 50-800 μm;
10) in the step 2), one printing needle head from G23-G30 is selected;
11) in the step 2), the advancing speed of the printing needle head in the spinning process is 0.1 mL/h-3 mL/h;
12) in the step 2), the voltage of the high-voltage module is minus 15kV to plus 15 kV;
13) in the step 2), the distance between the printing needle head and the receiving plate is 3 cm-30 cm;
14) in the step 2), the receiving plate and the loose layer on the receiving plate are ensured to be relatively static in the electrostatic spinning process;
15) the preparation method further comprises the step 3): drying the scaffold obtained in step 2).
As described above, the present invention has at least one of the following advantageous effects:
1) the loose layer in the double-layer guided bone regeneration bracket is beneficial to cell adhesion, interaction between cells and the bracket and bone tissue ingrowth, the compact layer is beneficial to blocking epithelial and connective tissue ingrowth, and the double-layer guided bone regeneration bracket prepared by the method has both a physical barrier function and a guided bone regeneration function.
2) The loose layer has a three-dimensional support structure, is prepared by a near-field direct-writing printing method, can accurately regulate and control the structure and the shape, and the compact layer is prepared by an electrostatic spinning method, so that pores among electrospun fibers are smaller, and the fibers are arranged more compactly.
3) The double-layer bone regeneration guiding scaffold is made of a high polymer material mixed with an osteogenesis promoting component and/or an antibacterial active component, the antibacterial active component can effectively prevent infection and control inflammation, and the osteogenesis nanometer component has an osteogenesis promoting function.
4) The mechanical and degradation properties of the double-layer bone regeneration guiding bracket are adjusted by changing the components, concentration and the like of the printing material, so that the requirements of clinical application on mechanical strength and degradation rate are met.
Drawings
Fig. 1 is a schematic structural diagram of a double-layer guided bone regeneration scaffold.
Fig. 2 is a structural diagram of a loose layer in a double-layer guided bone regeneration scaffold.
FIG. 3 is a rough photograph of an open layer and a dense layer.
Wherein A is a rough photograph of the porous layer; b is a rough photograph of the densified layer.
FIG. 4 is a scanning electron microscope image of the surface and cross section of the double-layer guided bone regeneration scaffold.
Wherein A is a scanning electron microscope picture of the loose layer side of the double-layer guide bone regeneration bracket; b is a scanning electron microscope picture of the compact layer side of the double-layer guide bone regeneration support; and C is a scanning electron microscope picture of the cross section of the double-layer guide bone regeneration support.
Fig. 5 is a graph showing the degradation curves of the double-layer guided bone regeneration scaffold in PBS solution and artificial saliva.
Wherein A is a degradation curve of the double-layer guide bone regeneration bracket in a PBS solution; and B is the degradation curve of the double-layer bone regeneration guiding scaffold in artificial saliva.
Fig. 6 ALP staining and ALP activity of the bi-layer guided bone regeneration scaffold.
Figure 7 qPCR results of cells seeded on a bilayer guided bone regeneration scaffold.
FIG. 8 shows the inhibition zones of the double-layer bone regeneration guiding scaffold on Escherichia coli and Staphylococcus aureus.
Wherein A is the inhibition zone of the double-layer bone regeneration guiding bracket to escherichia coli; b is the bacteriostatic circle of the double-layer bone regeneration guiding bracket to staphylococcus aureus.
Reference numerals:
1 loose layer
11 first loosening element
111 first support unit
12 second loosening element
121 second rack unit
2 dense layer
Detailed Description
The following description of the embodiments of the present invention is provided for illustrative purposes, and other advantages and effects of the present invention will become apparent to those skilled in the art from the present disclosure.
Please refer to fig. 1 to 8. It should be understood that the structures, ratios, sizes, and the like shown in the drawings and described in the specification are only used for matching with the disclosure of the specification, so as to be understood and read by those skilled in the art, and are not used to limit the conditions under which the present invention can be implemented, so that the present invention has no technical significance, and any structural modification, ratio relationship change, or size adjustment should still fall within the scope of the present invention without affecting the efficacy and the achievable purpose of the present invention. In addition, the terms "upper", "lower", "left", "right", "middle" and "one" used in the present specification are for clarity of description, and are not intended to limit the scope of the present invention, and the relative relationship between the terms and the terms is not to be construed as a scope of the present invention.
Example 1
A double-layer guided bone regeneration support comprises a loose layer 1 and a dense layer 2, wherein the dense layer 2 is arranged on the loose layer 1, the porosity of the loose layer 1 is 96%, the porosity of the dense layer is 55%, the thickness of the loose layer 1 is 0.41mm, the thickness of the dense layer 2 is 0.19mm, namely the thickness ratio of the loose layer 1 to the dense layer 2 is 2:1, the loose layer 1 comprises a plurality of first loose parts 11 and second loose parts 12 which are alternately arranged, the first loose parts 11 comprise a plurality of parallel first support units 111, the second loose parts 12 comprise a plurality of parallel second support units 121, the first support units 111 and the second support units 121 are crossed to form micropores, the first support units 111 of different first loose parts are arranged in parallel, the second support units 121 of different second loose parts are arranged in parallel, the distance between adjacent first support units in the same first loosening part is 400 mu m; the distance between adjacent second support units in the same second loosening component is 400 mu m, the first support unit is cylindrical, and the diameter of the first support unit is 10.2 mu m; the second holder element is cylindrical with a diameter of 10.2nm and the angle alpha at which the first holder element 111 intersects the second holder element 121 is 90 deg. between adjacent first and second loose parts 11, 12. And pre-drawing a CAD printing path according to the structure of the double-layer guide bone regeneration support. The compact layer 2 is composed of fibers with random arrangement directions, and the diameter of the fibers is 100 nm.
The preparation method of the double-layer bone regeneration guiding scaffold comprises the following steps:
1) 1.5g of polylactic-co-glycolic acid (PLGA), 0.75g of gelatin and 50mg of copper-containing mesoporous silicon nanoparticles are dissolved in hexafluoroisopropanol solvent to prepare printing ink with the total mass fraction of PLGA, gelatin and nanoparticles being 20%.
2) Loading the printing ink prepared in the step 1) into a printing cylinder, introducing a pre-drawn CAD printing path into a computer, and adjusting near-field electrostatic direct writing process parameters: the propelling air pressure is set to be 0.18MPa, the external high voltage is-4.5 kV, the receiving distance is 3mm, the moving speed of the printing nozzle is 25mm/s, materials in the printing material cylinder are stacked layer by layer according to a preset printing path under the action of a high-voltage electric field, and finally a preset (fiber spacing is 400 microns, the interweaving angle is 90 degrees, and 10 layers of loose layers (three-dimensional fiber supports) are obtained.
3) After the loose layer is prepared, the loose layer is used as a receiving device, and technological parameters of the near-field direct-writing printer are adjusted: the propelling speed of the propelling pump is 2.0mL/h, the external high voltage is 10kV, the distance between the spinning head and the receiving plate is adjusted to be about 12cm, and the compact layer nanofiber membrane is prepared on the spinning head in an electrostatic spinning mode. And (3) placing the finally prepared near-field direct-writing printing/electrostatic spinning double-layer nanofiber support in a vacuum drying oven for normal-temperature treatment for 12 hours to remove the non-volatile organic solvent for later use.
Example 2
The shape of the double-layer guided bone regeneration scaffold prepared by combining the near-field direct writing printing and the electrostatic spinning technology in the above embodiment 1 is characterized, and the result is shown in fig. 3. The rough photographs of the loose layer and the dense layer show that the loose layer fiber support structure is regular, the fibers are interwoven at 90 degrees, and the pores among the fibers are large and clear (fig. 3A); the fiber structure of the dense layer is dense, and the fiber arrangement direction is random (figure 3B). Scanning electron microscope results show that the loose layer has a regular structure, the diameter of a single fiber is 10.2 +/-0.5 mu m, the fibers are stacked layer by layer in a 90-degree interweaving mode, the distance between the fibers is 400 mu m, and the compact layer which is tightly interwoven among the fibers at the bottom can be seen through the loose layer (fig. 4A). Compared with the loose layer, the compact layer has fine, smooth and closely arranged fibers, the diameter of a single fiber is 96.5 +/-11.8 nm, the interweaving angle is irregular, and pores among the fibers are obviously reduced (figure 4B). It can be seen from the scanning electron microscope picture (fig. 4C) of the cross section of the double-layer guided bone regeneration scaffold that the loose layer and the dense layer are tightly bonded without delamination. The fibers of the section of the loose layer are arranged loosely, and the section of the compact layer is compact in structure.
Example 3
The degradation performance characterization is carried out on the double-layer guide bone regeneration scaffold prepared by combining the near-field direct writing printing and the electrostatic spinning technology in the embodiment 1. The prepared fiber scaffold was cut into a square of 10mm × 10 mm. Before the measurement begins, willEach film was weighed accurately, recording mass as m0. Subsequently, each sample was placed in a centrifuge tube containing 5mL of PBS (pH 7.4) or 5mL of artificial saliva (pH 7.4), and the centrifuge tube was incubated at 37 ℃ in a constant temperature shaker at a shaking speed of 100 rpm. When the preset time point is reached, completely cleaning the residual salt or enzyme solution on the surface of the fiber membrane by using deionized water, freeze-drying and weighing, and recording the mass as m1. The percent degradation of each sample at each time point can be calculated according to the following formula: percent (%) degradation [ [ (m)0-m1)/m0]×100％
The degradation experiment result is shown in fig. 5, the degradation speed of the double-layer guided bone regeneration scaffold in artificial saliva is faster than that in the PBS solution, and the double-layer guided bone regeneration scaffold is obviously degraded in the first 2 weeks. In the PBS solution, the degradation amount of the double-layer guided bone regeneration scaffold at 4w is about 26%, and the degradation amount at 12w is about 45% (fig. 5A); in the artificial saliva, the degradation amount of the double-layer bone regeneration guiding scaffold is about 40% at 4w, and the degradation amount is about 57% at 8 w; at 12w, the degradation amount reached about 70% (FIG. 5B). Therefore, the double-layer guided bone regeneration scaffold is supposed to be completely degraded within 4-6 months, and the degradation period of the double-layer guided bone regeneration scaffold is consistent with the clinically ideal degradation period of the double-layer guided bone regeneration scaffold.
Example 4
The double-layer guided bone regeneration scaffold prepared by combining the near-field direct writing printing and the electrostatic spinning technology in the embodiment 1 is subjected to in vitro osteogenesis activity detection. The prepared double-layer guide bone regeneration bracket is cut into a round piece with the size of a 24-hole plate, and the round piece is sterilized by ethylene oxide for later use. Rat bone marrow mesenchymal stem cells are cultured at 5 x 104The density of cells/well was seeded on the fibrous membrane in a 24-well plate (loose layer scaffold prepared by near-field direct-write printing was up), with 3 parallel per group. And after BMSCs adhere to the wall on the fiber membrane for 24 hours, the old culture medium is removed, the culture medium is replaced by an osteoinduction culture medium, and ALP staining and semi-quantitative detection are respectively carried out on the cells on the membrane when the preset time points (induction 4 and 7d) are reached. As a result, as shown in FIG. 6, ALP staining was significantly deepened on the bi-layer guided bone regeneration scaffold and ALP activity was significantly enhanced compared to the control group. In addition, the method can be used for producing a composite materialAnd qRT-PCR results after in vitro osteogenesis induction for 7d also show that the expression of osteogenesis related genes such as RUNX2, Col I, OCN and the like on the prepared double-layer guided bone regeneration scaffold is obviously enhanced (figure 7).
Example 5
The double-layer guided bone regeneration scaffold prepared by combining the near-field direct writing printing and the electrostatic spinning technology in the above example 1 was subjected to in vitro antibacterial activity analysis. The prepared double-layer guide bone regeneration bracket is cut into a round piece with the size of a 96-hole plate, and the round piece is sterilized by ethylene oxide for later use. And respectively placing the groups of fiber membranes on a solid culture medium coated with escherichia coli or staphylococcus aureus liquid, observing the formation condition of a bacteriostatic zone after 24 hours, and taking a picture. The results are shown in fig. 8, and compared with the control group, the experimental group formed an obvious zone of inhibition on escherichia coli and staphylococcus aureus, indicating that the compound has effective broad-spectrum antibacterial efficacy.
The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
1. The double-layer bone regeneration guiding support is characterized by comprising a loose layer (1) and a compact layer (2), wherein the compact layer (2) is arranged on the loose layer (1), the porosity of the loose layer (1) is 92% -98%, and the porosity of the compact layer is 40% -60%.
2. The double-layered guided bone regeneration scaffold according to claim 1, further comprising at least one of the following technical features:
1) the thickness ratio of the loose layer (1) to the dense layer (2) is 2: 1-5: 1;
2) the loose layer (1) has a regular structure;
3) the loose layer (1) is obtained by a near-field direct-writing printing method;
4) the compact layer (2) is composed of fibers with random arrangement directions;
5) the compact layer (2) is obtained by an electrostatic spinning method;
6) the loose layer (1) and the dense layer (2) are made of high polymer materials mixed with osteogenesis promoting components and/or antibacterial active components.
3. The double-layered guided bone regeneration scaffold according to claim 2, wherein in the step 2), the loose layer (1) comprises a plurality of first loose parts (11) and second loose parts (12) which are alternately arranged, the first loose parts (11) comprise a plurality of parallel first scaffold units (111), the second loose parts (12) comprise a plurality of parallel second scaffold units (121), and the first scaffold units (111) and the second scaffold units (121) are crossed to form micropores.
4. The double-layered guided bone regeneration scaffold according to claim 3, further comprising at least one of the following technical features:
a1) the first bracket units (111) of different first loosening parts are arranged in parallel;
a2) second bracket units (121) of different second loosening parts are arranged in parallel;
a3) the distance between adjacent first support units in the same first loosening component is 50-800 mu m; the distance between adjacent second bracket units in the same second loose part is 50-800 mu m;
a4) the first support unit is cylindrical and has the diameter of 10-100 mu m; the second bracket unit is cylindrical and has the diameter of 10-100 mu m;
a5) the angle alpha of the intersection of the first bracket unit (111) and the second bracket unit (121) in the adjacent first loosening part (11) and the second loosening part (12) is more than 0 degree and less than 180 degrees.
5. The double-layered guided bone regeneration scaffold according to claim 2, further comprising at least one of the following technical features:
41) in the feature 4), the diameter of the fiber is 100nm to 1500 nm;
61) in the characteristic 6), the polymer material is a synthetic polymer material and/or a natural polymer material;
62) the polymer material is characterized in that in the characteristic 6), the weight part of the polymer material is 5-20;
63) the characteristic 6) is that the osteogenesis promoting component is selected from one or more of hydroxyapatite, beta-tricalcium phosphate, bioactive glass, mesoporous silicon and graphene;
64) the bone formation promoting component is characterized in that 2-5 parts by weight of the bone formation promoting component is added;
65) in the characteristic 6), the antibacterial active component is selected from one or more of copper, zinc, magnesium, antibacterial peptide and antibiotics;
66) the antibacterial active ingredient is 0.1-1 part by weight in the characteristic 6).
6. The method for preparing a double-layered scaffold for guided bone regeneration according to any one of claims 1 to 5, comprising the steps of:
1) preparing and obtaining the loose layer (1) by adopting a near-field direct-writing printing method;
2) taking the loose layer (1) obtained in the step 1) as a receiving device, and preparing the dense layer (2) by an electrostatic spinning method.
7. The method for preparing the double-layered guided bone regeneration scaffold according to claim 6, wherein the printed material of step 1) and the electrospun material of step 2) are heated and melted or dissolved in a solvent, and then prepared.
8. The method for preparing a double-layer guided bone regeneration scaffold according to claim 7, further comprising at least one of the following technical features:
1) the printing material of the step 1) and the electrostatic spinning material of the step 2) are high molecular materials mixed with components contributing to bone and/or antibacterial active components;
2) the solvent is selected from one or more of water, trichloromethane, dichloromethane, tetrahydrofuran, hexafluoroisopropanol, acetone and dimethyl sulfoxide;
3) the mass ratio of the solvent to the printing material of the step 1) and the electrostatic spinning material of the step 2) is 74: 26-92.9: 7.1.
9. the method for preparing the double-layer guided bone regeneration scaffold according to claim 8, wherein the method in feature 1) further comprises at least one of the following technical features:
11) the high polymer material is a synthetic high polymer material and/or a natural high polymer material;
12) the weight part of the high polymer material is 5-20;
13) the osteogenesis promoting component is selected from one or more of hydroxyapatite, beta-tricalcium phosphate, bioactive glass, mesoporous silicon and graphene;
14) the bone promoting component accounts for 2-5 parts by weight;
15) the antibacterial active component is selected from one or more of copper, zinc, magnesium, antibacterial peptide and antibiotics;
16) the weight part of the antibacterial active component is 0.1-1.
10. The method for preparing a double-layer guided bone regeneration scaffold according to claim 6, further comprising at least one of the following technical features:
1) in the step 1), the printing temperature is 50-400 ℃;
2) in the step 1), one printing needle head from G23 to G30 is selected;
3) in the step 1), the air pressure of a material cylinder of the printing material is 500 kPa-2000 kPa;
4) in the step 1), the voltage of the high-voltage module is minus 50kV to plus 50 kV;
5) in the step 1), the distance between the printing needle head and the receiving plate is 1-5 mm;
6) in the step 1), the moving speed of the printing nozzle is 20-200 mm/s;
7) in the step 1), the diameter of the printing wire drawing is 10-100 μm;
8) in the step 1), the fiber interweaving angle is more than 0 degree and less than 180 degrees;
9) in the step 1), the fiber spacing is 50-800 μm;
10) in the step 2), one printing needle head from G23-G30 is selected;
11) in the step 2), the advancing speed of the printing needle head in the spinning process is 0.1 mL/h-3 mL/h;
12) in the step 2), the voltage of the high-voltage module is minus 15kV to plus 15 kV;
13) in the step 2), the distance between the printing needle head and the receiving plate is 3 cm-30 cm;
14) in the step 2), the receiving plate and the loose layer on the receiving plate are ensured to be relatively static in the electrostatic spinning process;
15) the preparation method further comprises the step 3): drying the scaffold obtained in step 2).
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| CN115025628A (en) * | 2022-05-10 | 2022-09-09 | 厦门大学 | Composite nanofiber air filter membrane and preparation device and preparation method thereof |
| CN118178054A (en) * | 2024-05-17 | 2024-06-14 | 中山大学 | Bone regeneration guiding bracket with hierarchical pore structure and preparation method and application thereof |
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