CN115054728A - Bionic bone tissue engineering scaffold material and preparation method thereof - Google Patents
Bionic bone tissue engineering scaffold material and preparation method thereof Download PDFInfo
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- CN115054728A CN115054728A CN202210841681.9A CN202210841681A CN115054728A CN 115054728 A CN115054728 A CN 115054728A CN 202210841681 A CN202210841681 A CN 202210841681A CN 115054728 A CN115054728 A CN 115054728A
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Abstract
The invention provides a bionic bone tissue engineering scaffold and a preparation method thereof. The bionic bone tissue engineering scaffold consists of a base body, a bionic layer and a gel layer containing a bone growth promoting growth factor BMP-2 and antibacterial peptide, wherein the base body is obtained by a 3D printing method, then the base body is modified by dopamine, and is soaked in an aqueous solution of I-type collagen fibers and sodium alginate and then is frozen and dried to form the bionic layer; then immersing the bionic bone tissue engineering scaffold in chitosan/polyvinyl alcohol gel liquid containing bone growth promoting factors BMP-2 and antibacterial peptide, and then placing the bionic bone tissue engineering scaffold in an incubator to form gel so as to obtain the bionic bone tissue engineering scaffold. The bionic bone tissue engineering scaffold has excellent mechanical strength and biocompatibility similar to human bones, and can treat bone defects and simultaneously slowly release antibacterial drugs to prevent postoperative infection.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a bionic bone tissue engineering material and a preparation method thereof.
Background
At present, the clinical problem of large-scale bone defects caused by trauma, infection and tumor resection is not solved effectively. The repair of bone defects is one of the important subjects of bone tissue engineering, and the development of bone tissue engineering also provides a new idea for solving the difficult problem of bone defect repair.
Bone tissue engineering is generally considered to comprise three major elements: scaffold material, cells and growth factors. The bone tissue engineering scaffold plays a role in supporting the structure in vivo, and also plays a role in cell adhesion, growth, propagation and providing a place for tissue regeneration. The ideal bone tissue engineering material is an ideal bone substitute and has the performance of inducing bone cells to form mineralized tissues.
Among inorganic materials, hydroxyapatite/calcium phosphate is a main component of human bones and teeth, has good biocompatibility, can be combined with human bones and induce the formation of new bones, but has the defects of high brittleness, low bending strength of materials and the like in application, and is often compounded with polymers in the prior art to overcome the defect.
A composite material of silk fibroin and calcium phosphate is synthesized by using an in-situ synthesis method and a method combining a soluble salt pore-forming method and a freezing drying method to prepare the composite scaffold of the silk fibroin and the nano calcium phosphate with a macroporous/micro porous single/nano-sized calcium phosphate aggregates with porous for bone-tissue-engineering applications, Nanomedicine,2013,8(3) and 359-378. However, the human compact bone has a compressive strength of 133-197MPa, while the compressive strength of the scaffold is 0.62MPa, which is relatively low, and thus, a good function of replacing human bones cannot be realized. -h.jegal, j. -h.park, j. -h.kim, t. -h.kim, u.s.shin, t. -i.kim and h. -w.kim.functional composite nanoparticles of poly (lactic-co-glycolic) connective tissue-adaptive bone elementary precursor for bone regeneration. acta biomaterials.2011; 1609-1617 the lactic acid-polycaprolactone copolymer (PLCL) fibrous membrane and the PLCL fibrous membrane added with gelatin and apatite are prepared by adopting an electrostatic spinning technology, and the results of the implantation of the rat skull for 6 weeks show that the fibrous structure can effectively promote the growth of new bones, and the addition of the gelatin and the apatite enhances the bone-promoting effect. However, the fiber-based bone repair scaffold prepared by the method is in a membrane shape, the requirements of bone defects with different shapes on the implant are not easily met, the compact filling is not easily carried out, and the scaffold does not have any mechanical strength and can not provide any mechanical support at the bone defect part after being implanted.
Meanwhile, at present, the composite scaffold of the polymer material and the inorganic material is mostly prepared by a freeze-drying method, a dissolved salt pore-forming method and a mold casting method, and for example, the composite scaffold has the defects of long preparation time, high mold preparation cost, difficulty in controlling the size and the shape of the pore diameter and the like.
The bionic model of the bone repair scaffold is the natural bone tissue ECM, the main component of the natural bone tissue ECM is mineralized type I collagen, and the type I collagen fiber and hydroxyapatite crystal are orderly arranged to form mature bone matrix. Research shows that the fiber structure of the ECM-like has a good promoting effect on the repair of various tissues, and related cells (osteoblasts, Mesenchymal Stem Cells (MSCs) and the like) in bone tissues also have a certain recognition function on fiber topological structures, so that the bone repair scaffold can provide a suitable three-dimensional environment for cell adhesion growth and bone tissue repair. The tissue engineering bone material which has good mechanical property, bionic function and mineralized fiber structure and is similar to the human skeleton performance can not be prepared in the prior art. Meanwhile, the problem of postoperative infection is also a big problem after bone grafting operation, and if the bone tissue engineering scaffold can provide good support and bionic performance and has certain antibacterial performance, the scaffold is more favorable for postoperative recovery of patients. Meanwhile, the research finds that the performance of the chitosan/polyvinyl alcohol blending material is superior to that of pure chitosan in many aspects, the blending system has temperature sensitivity under certain conditions, gel-sol transformation occurs at body temperature, and factors and/or medicaments can be slowly and stably released along with the diffusion of the factors and/or the medicaments and the self degradation of the gel. Therefore, the bone repair scaffold is specially constructed, solves the donor problem of a wide range of bone defects, and better meets the requirements in bone defect operation and repair.
Disclosure of Invention
In order to overcome the defects and shortcomings of the prior art, the invention provides a bionic bone tissue engineering material which has excellent mechanical strength and biocompatibility and can treat bone defects and simultaneously slowly release antibacterial drugs to prevent postoperative infection and a preparation method thereof.
A bionic bone tissue engineering scaffold is characterized by comprising a substrate, a bionic layer and a gel layer containing a bone growth promoting factor BMP-2 and antibacterial peptide, wherein the substrate is obtained by poly (caprolactone-co-lactide), tussah silk fibroin and hydroxyapatite through a 3D printing method, then the substrate is modified by dopamine to obtain a dopamine modified substrate, then I type collagen short fibers are uniformly dispersed in a sodium alginate aqueous solution, the dopamine modified substrate is soaked in an aqueous solution of the I type collagen short fibers and the sodium alginate and then taken out, freeze drying is carried out, and the bionic layer is formed outside the substrate to obtain the scaffold with the bionic layer; immersing the bracket with the bionic layer in a negative pressure environment in chitosan/polyvinyl alcohol gel liquid containing bone growth promoting factors BMP-2 and antibacterial peptide, standing for 12-24h at 4 ℃, and then placing the bracket in an incubator at 37 ℃ to form gel so as to obtain the bionic bone tissue engineering bracket.
In the matrix scaffold, the mass ratio of the poly (caprolactone-co-lactide), the tussah silk fibroin and the hydroxyapatite is (40-70): (6-10): (30-40), the molecular weight of the poly (caprolactone-co-lactide) is 500-1000kDa, and the monomer molar ratio of caprolactone to lactide of the poly (caprolactone-co-lactide) is (70-30): (30-70). The length of the type I collagen short fiber is 0.1mm-2mm, preferably 0.2mm-1mm, more preferably 0.3-0.8 mm. The concentration of the sodium alginate aqueous solution is 5-25 wt%, and the mass ratio of the type I short fibers to the sodium alginate is (70-80): (20-30). The antibacterial peptide is epsilon-polylysine, L-polyarginine or poly L-glutamic acid. The concentrations of BMP-2 and antibacterial peptide in the chitosan/polyvinyl alcohol gel liquid containing the osteogenesis promoting factor BMP-2 and the antibacterial peptide are respectively 150-200 mu g/ml and 300-400 mu g/ml.
Wherein, the bone growth promoting factor BMP-2 can be replaced by a mixture of the bone growth promoting factor BMP-2 and the vascular endothelial cell growth factor VEGF, and the mass ratio of the bone growth promoting factor BMP-2 to the vascular endothelial cell growth factor VEGF is preferably 5-10: 1, the total concentration of which in the gel liquid is 150-200 mu g/ml.
The preparation method of the bionic bone tissue engineering scaffold comprises the following steps: (1) sequentially adding poly (caprolactone-co-lactide), tussah silk fibroin and hydroxyapatite into trifluoroethanol according to a mass ratio, uniformly mixing to form slurry, carrying out 3D printing, and then carrying out freeze drying treatment on the printed scaffold for more than 12 hours to obtain a matrix; (2) putting the substrate into a dopamine Tris-HCl solution for reaction to obtain a dopamine-modified substrate; uniformly dispersing the type I collagen short fibers in a sodium alginate aqueous solution, soaking the dopamine-modified substrate in the aqueous solution of the type I collagen short fibers and the sodium alginate, taking out, and carrying out freeze drying treatment for 4-8 hours to form a bionic layer outside the substrate, thereby obtaining a substrate bracket with the bionic layer; (3) immersing the substrate scaffold with the bionic layer in a chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and antibacterial peptide by a physical solution method under a negative pressure environment, standing for 12-24h at 4 ℃, and then placing the substrate scaffold in an incubator at 37 ℃ to form gel, thereby obtaining the bionic bone tissue engineering scaffold;
the 3D printing method in the step (1) comprises the following steps: obtaining a three-dimensional model of the bone defect through a three-dimensional reconstruction technology according to the acquired CT scanning tomographic data of the autologous bone to be repaired; and printing the composite slurry into a required shape according to the three-dimensional model, and then carrying out freeze drying treatment on the printed scaffold for more than 12 hours, so as to keep the morphology of the scaffold from shrinking, and simultaneously removing the solvent in the scaffold, thereby obtaining the porous matrix of the bone tissue engineering scaffold.
The pressing speed is set to 0.006-0.01mm/s and the XY stage moving speed may be 2.0-3.0mm/s when 3D printing is used. For example: the extrusion speed is selected to be 0.008mm/s, the XY platform movement speed is 2.5mm/s, and the extrusion speed can be finely adjusted according to the actual situation so as to obtain the best printing process.
The pH value of the dopamine Tris-HCl solution in the step (2) is 7.5-8.5, the concentration is 0.5-1.5 wt%, and the reaction time is 2-24 h.
The preparation method of the I-type collagen fiber in the step (2) comprises the steps of adding the I-type collagen into 1.0mol/L acetic acid solution, stirring until the I-type collagen is completely dissolved, and defoaming to obtain spinning dope, wherein the concentration of the collagen in the spinning dope is 3-5 wt%. The type I collagen fiber is formed by adopting an electrostatic spinning method, and the type I collagen short fiber is obtained by cutting. The type I collagen staple fibers have a length of 0.1mm to 2mm, preferably 0.2mm to 1mm, more preferably 0.5 to 0.8 mm.
The preparation method of the chitosan/polyvinyl alcohol mixed gel liquid containing BMP-2 and antibacterial peptide in the step (3) comprises the following steps: 1) mixing NaHCO3 solution with concentration of 0.5-0.6mol/L and polyvinyl alcohol solution with concentration of 0.5-3 wt%, taking a certain amount of chitosan hydrochloric acid solution with concentration of 1.5-2.5 wt%, placing for 15min in ice bath, slowly dropwise adding mixed solution of NaHCO3 and polyvinyl alcohol into the chitosan hydrochloric acid solution under ice bath and magnetic stirring, after dropwise adding, directly adding BMP-2 and antibacterial peptide into the mixed solution, continuously stirring for 20min, and ensuring uniform mixing to obtain the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and antibacterial peptide. The concentrations of BMP-2 and the antimicrobial peptide in the gel liquid are respectively 150-.
The matrix scaffold with the bionic layer is immersed in chitosan/polyvinyl alcohol mixed gel liquid containing BMP-2 and antibacterial peptide under the negative pressure environment by a physical solution method, stands for 12-24 hours at 4 ℃, is placed in an incubator at 37 ℃ and forms gel after 2-24 hours.
When the bone growth promoting factor BMP-2 is replaced by a mixture of the bone growth promoting factor BMP-2 and the vascular endothelial cell growth factor VEGF, replacing the bone growth promoting factor BMP-2 in the preparation method by a mixture of the bone growth promoting factor BMP-2 and the vascular endothelial cell growth factor VEGF, preferably, the mass ratio of the bone growth promoting factor BMP-2 to the vascular endothelial cell growth factor VEGF is 5-10: 1, the total concentration of the complex in the gel liquid is 150-200 mu g/ml.
The poly (caprolactone-co-lactide) has good mechanical property, bioactivity and biodegradability, the degradation speed of the poly (caprolactone-co-lactide) can be adjusted by the proportion of the caprolactone to the lactide, and the good mechanical property of the poly (caprolactone-co-lactide) is favorable for the bone scaffold to play a good supporting role.
The tussah silk fibroin is one of silk fibroin, is a high-purity protein secreted by endothelial cells on the inner wall of tussah silk gland, mainly comprises glycine, alanine and serine in amino acid composition, has good biocompatibility, is nontoxic to cells and organisms, and does not or less cause inflammation and immunological rejection reaction. In most of researches or reports on silk fibroin materials, the raw material used is silkworm silk. Compared with the tussah silk fibroin, the tussah silk fibroin contains a special arginine-glycine-aspartic acid (RGD) tripeptide sequence in the molecule. The RGD sequence is used as a recognition site for combination of a cell membrane integrin receptor and an extracellular ligand, mediates interaction between cells and extracellular matrix and between cells, and can promote recognition and adhesion of the cells to the scaffold.
The 3D printing is an integrated molding additive manufacturing technology, the traditional material reduction manufacturing technology is changed, the printing efficiency can be greatly improved, the structure of a product can be accurately designed, and the requirement of personalized treatment is met. The matrix of the bone tissue engineering scaffold with accurate structure, good mechanical property and cell adhesion promoting performance is obtained by 3D printing of poly (caprolactone-co-lactide), tussah silk fibroin and hydroxyapatite.
The marine mussel secretes adhesive protein through byssus, the protein contains rich L-3, 4-Dihydroxyphenylalanine (DOPA) and has super-strong adhesive capacity, dopamine with a structure similar to that of the DOPA can simulate the adhesive performance of the marine mussel, a polydopamine coating can be precipitated on the surface of a substrate, various components and the like are directly fixed, the method is simple, an organic solvent is not used in the reaction, and the condition is mild.
The polypeptide antibacterial agents such as epsilon-polylysine, L-polyarginine and the like have the same antibacterial and anti-inflammatory effects as chemical antibacterial agents such as nano inorganic silver, quaternary ammonium salt and the like, can hydrolyze insoluble mucopolysaccharide of germ cell walls, can also be directly combined with virus protein with negative charges to inactivate various viruses, and the antibacterial peptides have good stability and almost have no toxic or harmful effect on normal cells of higher animals.
The chitosan/polyvinyl alcohol blending material has better performance than pure chitosan in many aspects, the blending system has temperature sensitivity under certain conditions, gel-sol transformation occurs at body temperature, and factors and/or medicaments can be slowly and stably released along with the diffusion of the factors and/or the medicaments and the self degradation of gel.
Compared with the prior art, the invention has the beneficial effects that:
(1) the bionic bone tissue engineering scaffold prepared by the invention has good mechanical property and biodegradability, the degradation speed of the scaffold can be adjusted by adjusting the proportion of caprolactone to lactide, and excellent mechanical property can be obtained by adjusting the proportion of each component of the matrix and selecting a 3D printing technology. According to the research, the compressive strength of human compact bone is 133-197MPa, the compressive strength of a plurality of bone scaffold materials in the prior art is very small, and the compressive strength of the bionic bone tissue engineering scaffold material can reach 135-158MPa by selecting the components of the matrix and the 3D printing technology, is similar to the compressive strength of human bone, and can play a good supporting role. And the 3D printing technology can prepare the bionic bone tissue engineering scaffold with the shape similar to the shape of the bone defect, solves the problem of donor shortage in clinic and provides a donor with excellent performance for the operation of the bone defect with the complex shape.
(2) The hydroxyapatite and I-type collagen fiber in the bionic bone tissue engineering scaffold prepared by the invention are similar to the main components of the ECM of a natural bone tissue, and have a better promotion effect on the repair of various tissues, and related cells (osteoblasts, mesenchymal stem cells and the like) in the bone tissue also have a certain recognition function on a fiber topological structure, so that the bionic bone tissue engineering scaffold can provide a suitable three-dimensional environment for cell adhesion growth and bone tissue repair. The dopamine can simulate the adhesion performance of mussels, a polydopamine coating can be deposited on the surface of a substrate, various components and the like can be directly fixed, the method is simple, no organic solvent is used in the reaction, and the method is green and environment-friendly.
(3) The polypeptide antibacterial agent used by the invention has the same antibacterial and anti-inflammatory effects as chemical antibacterial agents such as nano inorganic silver, quaternary ammonium salt and the like, can hydrolyze insoluble mucopolysaccharide of germ cell walls, can also be directly combined with virus protein with negative charges to inactivate various viruses, and the antibacterial peptide has good stability and almost has no toxic or harmful effect on normal cells of higher animals. Meanwhile, the hydrogel slow-release antibacterial drug with good biological temperature sensitivity is selected to prevent postoperative infection, the antibacterial peptide can be released at the first time of implanting the bionic bone tissue engineering scaffold and can be released continuously within 24 hours, the antibacterial peptide and the degraded chitosan act together to prevent postoperative infection in a period of time just after the operation, and the chitosan still can play an antibacterial role within a certain time in the degradation process of the residual chitosan. The hydrogel slowly releases the bone growth factor BMP-2, so that the release time of the factor is prolonged.
Drawings
Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are only for purposes of illustrating the preferred embodiments and are not to be construed as limiting the embodiments of the invention. Also, like reference numerals are used to refer to like parts throughout the drawings.
FIG. 1 is an electron microscope image of the scaffolds for bionic bone tissue engineering of example 1.
Detailed Description
Example 1:
step 1, preparation of a substrate.
And obtaining a three-dimensional model of the bone defect by a three-dimensional reconstruction technology according to the acquired CT scanning tomographic data of the autologous bone to be repaired. 20g of the polylactic acid has the molecular weight of 500KPa and the ratio of caprolactone to lactide monomer of 30: 70 g of poly (caprolactone-co-lactide), 3g of tussah silk fibroin and 20g of hydroxyapatite are sequentially added into trifluoroethanol and uniformly mixed to form slurry. Preparing a base material by using the slurry through a 3D printing method; when 3D printing is used, the extrusion speed is selected to be 0.008mm/s, and the XY platform movement speed is selected to be 2.5 mm/s. And (4) carrying out freeze drying treatment on the scaffold obtained by 3D printing for 16h to obtain the matrix scaffold.
And 2, preparing the substrate bracket with the bionic layer.
And (3) putting the substrate scaffold prepared in the step (1) into a dopamine Tris-HCl solution with the pH value of 7.5 and the concentration of 0.5 wt%, and reacting for 2 hours to form the substrate scaffold material adhered with dopamine. Then 3g I short collagen fiber is uniformly dispersed in 5-25% sodium alginate aqueous solution with mass volume percentage, the porous matrix support material adhered with dopamine is soaked in the mixed aqueous solution of I type collagen fiber and sodium alginate, the mass ratio of the I type short collagen fiber to the sodium alginate is 70: 30, taking out after dipping for 12h, freeze-drying for 6h, and forming a bionic layer outside the matrix stent.
And 3, preparing a chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and epsilon-polylysine to prepare the bionic bone tissue engineering scaffold material.
Mixing 0.5mol/L NaHCO3 solution with 0.5% polyvinyl alcohol solution, taking a certain amount of 1.6% chitosan hydrochloric acid solution, placing for 15min in ice bath, slowly dropwise adding mixed solution of NaHCO3 and polyvinyl alcohol into the chitosan hydrochloric acid solution under ice bath and magnetic stirring, after dropwise adding, directly adding BMP-2 and epsilon-polylysine into the mixed solution according to the proportion that the concentrations of the BMP-2 and the epsilon-polylysine in the gel solution are 150 mu g/ml and 300 mu g/ml respectively, and continuously stirring for 20min until uniform mixing is achieved, thus obtaining the chitosan/polyvinyl alcohol mixed gel solution containing the BMP-2 and the epsilon-polylysine.
Immersing the substrate scaffold material with the bionic layer prepared in the step 2 in the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and epsilon-polylysine prepared in the step 3 under the negative pressure environment by a physical solution method, standing for 12-24 hours at 4 ℃, then placing in an incubator at 37 ℃, and forming gel after 6 hours.
Example 2:
step 1, preparation of a substrate.
And obtaining a three-dimensional model of the bone defect by a three-dimensional reconstruction technology according to the acquired CT scanning tomographic data of the autologous bone to be repaired. 25g of caprolactone-lactide monomer with a molecular weight of 750KPa in a ratio of 50: 50 g of poly (caprolactone-co-lactide), 4g of tussah silk fibroin and 18g of hydroxyapatite are sequentially added into 100ml of trifluoroethanol and uniformly mixed to form slurry. Preparing a base material by using the slurry through a 3D printing method; when 3D printing is used, the extrusion speed is selected to be 0.008mm/s, and the XY platform movement speed is selected to be 2.5 mm/s. And (4) carrying out freeze drying treatment on the scaffold obtained by 3D printing for 16h to obtain the matrix scaffold.
And 2, preparing the substrate bracket with the bionic layer.
And (3) putting the substrate scaffold prepared in the step 1 into a dopamine Tris-HCl solution with the pH value of 8 and the concentration of 1 wt%, and reacting for 12 hours to form the substrate scaffold material adhered with dopamine. Then 3g I short collagen fibers are uniformly dispersed in a sodium alginate aqueous solution with the concentration of 5 percent by mass volume, the porous matrix stent material adhered with dopamine is soaked in a mixed aqueous solution of I type collagen fibers and sodium alginate, and the mass ratio of the I type short collagen fibers to the sodium alginate is 70: 30, taking out after dipping for 12h, freeze-drying for 6h, and forming a bionic layer outside the matrix stent.
And 3, preparing a chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and L-polyarginine to further prepare the bionic bone tissue engineering scaffold material.
Mixing NaHCO3 solution with concentration of 0.5mol/L with polyvinyl alcohol solution with concentration of 1.5%, taking a certain amount of 1.8 wt% chitosan hydrochloric acid solution, placing for 15min under ice bath, slowly dropwise adding mixed solution of NaHCO3 and polyvinyl alcohol into the chitosan hydrochloric acid solution under ice bath and magnetic stirring, after dropwise adding, directly adding BMP-2 and L-polyarginine into the mixed solution according to the proportion that the concentrations of BMP-2 and L-polyarginine in the gel solution are 180 mu g/ml and 360 mu g/ml respectively, and continuously stirring for 20min until uniform mixing is achieved, thus obtaining the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and L-polyarginine.
Immersing the substrate scaffold material with the bionic layer prepared in the step 2 in the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and antibacterial peptide prepared in the step 3 under a negative pressure environment by a physical solution method, standing for 12 hours at 4 ℃, and then placing in an incubator at 37 ℃ to form gel after 2 hours.
Example 3:
step 1, preparation of a substrate.
And obtaining a three-dimensional model of the bone defect by a three-dimensional reconstruction technology according to the acquired CT scanning tomographic data of the autologous bone to be repaired. 35g of caprolactone with molecular weight of 1000KPa and a lactide monomer ratio of 70: 30 g of poly (caprolactone-co-lactide), 5g of tussah silk fibroin and 15g of hydroxyapatite are sequentially added into trifluoroethanol and uniformly mixed to form slurry. Preparing a base material by using the slurry through a 3D printing method; when 3D printing is used, the extrusion speed is 0.01mm/s, and the XY platform movement speed is 2.5 mm/s. And (5) carrying out freeze drying treatment on the scaffold obtained by 3D printing for 12h to obtain the matrix scaffold.
And 2, preparing the substrate bracket with the bionic layer.
And (3) putting the substrate scaffold prepared in the step (1) into a dopamine Tris-HCl solution with the pH value of 8.5 and the concentration of 1.5 wt%, and reacting for 24 hours to form the substrate scaffold material adhered with dopamine. Then 3g I short collagen fiber is uniformly dispersed in sodium alginate aqueous solution with the concentration of 15 wt% by mass volume, the porous matrix support material adhered with dopamine is soaked in mixed aqueous solution of I type collagen fiber and sodium alginate, and the mass ratio of the I type short collagen fiber to the sodium alginate is 70: 30, taking out after dipping for 12h, freeze-drying for 6h, and forming a bionic layer outside the matrix stent.
And 3, preparing a chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and poly L-glutamic acid to further prepare the bionic bone tissue engineering scaffold material.
Mixing NaHCO3 solution with concentration of 0.6mol/L with polyvinyl alcohol solution with concentration of 3 wt%, taking a certain amount of chitosan hydrochloric acid solution with concentration of 1.6-2 wt%, placing for 15min in ice bath, slowly dropwise adding mixed solution of NaHCO3 and polyvinyl alcohol into the chitosan hydrochloric acid solution under ice bath and magnetic stirring, after dropwise adding, directly adding BMP-2 and poly L-glutamic acid into the mixed solution according to the proportion that the concentrations of BMP-2 and poly L-glutamic acid in the gel solution are 200 mug/ml and 400 mug/ml respectively, and continuously stirring for 20min until uniform mixing is achieved, thus obtaining the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and poly L-glutamic acid.
Immersing the substrate scaffold material with the bionic layer prepared in the step 2 in the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and poly L-glutamic acid prepared in the step 3 under the negative pressure environment by a physical solution method, standing for 12-24 hours at 4 ℃, and then placing in an incubator at 37 ℃ to form gel after 12 hours.
Example 4:
the preparation method is the same as that in example 3, except that BMP-2 in example 3 is replaced by a mixture of bone growth promoting factor BMP-2 and vascular endothelial cell growth factor VEGF, and the mass ratio of the bone growth promoting factor BMP-2 to the vascular endothelial cell growth factor VEGF is 9: 1, wherein the concentration of the bone growth promoting factor BMP-2 in the gel liquid is 180 mu g/ml, and the concentration of the VEGF in the gel liquid is 20 mu g/ml.
Example 5: and (5) testing the performance of the bracket.
The biomimetic bone tissue engineering scaffold material of example 1 was characterized under a scanning electron microscope (purchased from japan company, model number JSM-7500) and the scanning electron microscope image is shown in fig. 1.
And (3) testing the compressive strength: the bionic bone tissue engineering scaffold material was subjected to a compressive strength test by an electronic universal material testing machine (available from INSTRON corporation, model number INSTRON 3365), and the scaffolds of examples 1 to 4 measured compressive strengths of 135MPa, 146MPa, 158MPa and 158MPa, respectively, which were similar to the compressive strength of compact bones of human bodies, and the samples were not damaged by the compressive test.
And (3) antibacterial experiment: the bacteriostatic test was carried out according to the standard of "JISZ 2801-2000" antibacterial processed product-antibacterial property test method and antibacterial effect ", using the following experimental strains: (iii) Escherichia coli (ATCC 25922), Streptococcus pneumoniae (ATCC 49619), and Staphylococcus aureus (ATCC 25923). The antibacterial rates of the bionic bone tissue engineering scaffolds prepared in the examples 1-4 on strains I, II and III are shown in the following table. The bionic bone tissue engineering scaffold obtained by the invention has excellent antibacterial effect.
| Escherichia coli | Streptococcus pneumoniae | Staphylococcus aureus | |
| Example 1 | 95％ | 96％ | 95％ |
| Example 2 | 97％ | 98％ | 97％ |
| Example 3 | 99％ | 99％ | 99％ |
| Example 4 | 99％ | 99％ | 99％ |
Table 1: results of the antibacterial test of the scaffolds for biomimetic bone tissue engineering of examples 1-4
The bone tissue engineering scaffold of example 3 was placed in simulated human body fluid and tested for antibacterial properties against staphylococcus aureus at 24h, 48h and 7 th days of degradation, respectively, with the following results.
| 0h | 24h | 48h | 7d | |
| Example 3 | 99％ | 98％ | 98％ | 80％ |
Table 2: example 3 results of antibacterial experiments after degradation of the scaffolds for bionic bone tissue engineering for different periods of time
According to the experimental result, the combined action of the chitosan and the antibacterial peptide realizes the antibacterial property at the initial degradation stage, the antibacterial property is relatively stable all the time due to the existence of the slow release effect, the antibacterial peptide is basically released up to the seventh day, and the whole bionic bone tissue engineering scaffold still shows good antibacterial property due to the antibacterial effect of the chitosan.
Example 6: in vitro release experiments.
Because the slow release of the mixture of BMP-2/BMP-2 and VEGF and the antibacterial peptide is mainly realized by using the chitosan/polyvinyl alcohol mixed gel, the in-vitro release condition of the chitosan/polyvinyl alcohol gel containing the mixture of BMP-2/BMP-2 and VEGF and the antibacterial peptide is mainly studied.
The chitosan/polyvinyl alcohol mixed gel solutions containing the BMP-2/BMP-2 and VEGF mixture and the antibacterial peptide of examples 1 to 4 were placed in incubators at 37 ℃ respectively, and gels were formed after 6 hours. In vitro release experiments on the four gels containing the BMP-2/BMP-2 and VEGF mixture and the antibacterial peptide in phosphate buffer pH7.4 at 37 ℃ showed that the four gels showed significant sustained release behavior, and the in vitro release rate was slow with increasing drug loading, probably due to the increased interaction between BMP-2 and the antibacterial peptide and the material with increasing drug loading.
It should also be 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. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in the process, method, article, or apparatus that comprises the element.
As will be appreciated by one skilled in the art, embodiments of the present application may be provided as a method, system, or computer program product. Accordingly, the present application may take the form of an entirely hardware embodiment, an entirely software embodiment or an embodiment combining software and hardware aspects. Furthermore, the present application may take the form of a computer program product embodied on one or more computer-usable storage media (including, but not limited to, disk storage, CD-ROM, optical storage, and the like) having computer-usable program code embodied therein.
The above are merely examples of the present application and are not intended to limit the present application. Various modifications and changes may occur to those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the scope of the claims of the present application.
Claims (10)
1. A bionic bone tissue engineering scaffold is characterized by comprising a substrate, a bionic layer and a gel layer containing bone growth promoting factor BMP-2 and antibacterial peptide, wherein the substrate is obtained by poly (caprolactone-co-lactide), tussah silk fibroin and hydroxyapatite through a 3D printing method, then the substrate is modified by dopamine to obtain a dopamine modified substrate, then I type collagen short fibers are uniformly dispersed in a sodium alginate aqueous solution, the dopamine modified substrate is soaked in an aqueous solution of I type collagen fibers and sodium alginate and then taken out, freeze drying is carried out, and the scaffold with the bionic layer is obtained by forming the bionic layer outside the substrate; immersing the bracket with the bionic layer in a chitosan/polyvinyl alcohol gel solution containing bone growth promoting factors BMP-2 and antibacterial peptide under a negative pressure environment, standing for 12-24h at 4 ℃, and then placing the bracket in an incubator at 37 ℃ to form gel so as to obtain the bionic bone tissue engineering bracket;
wherein the mass ratio of the poly (caprolactone-co-lactide), the tussah silk fibroin and the hydroxyapatite in the matrix is (40-70): (6-10): (30-40), the molar ratio of the caprolactone to the lactide monomer used for preparing the poly (caprolactone-co-lactide) is (70-30): (30-70), the molecular weight of the poly (caprolactone-co-lactide) is 500-1000 kDa; the length of the type I collagen short fiber is 0.1mm-2 mm; the mass ratio of the type I collagen short fiber to the sodium alginate is (70-80): (30-20); the concentrations of BMP-2 and antibacterial peptide in the chitosan/polyvinyl alcohol gel liquid containing the osteogenesis promoting factor BMP-2 and the antibacterial peptide are respectively 150-200 mu g/ml and 300-400 mu g/ml.
2. The biomimetic bone tissue engineering scaffold according to claim 1, wherein the concentration of the aqueous sodium alginate solution is 5-25 wt%.
3. The scaffolds for biomimetic bone tissue engineering according to claim 1 or 2, wherein the antibacterial peptide is epsilon-polylysine, L-polyarginine or poly-L-glutamic acid.
4. The scaffolds for the tissue engineering of biomimetic bone according to claim 1 or 2, wherein the concentrations of BMP-2 and antibacterial peptide in the chitosan/polyvinyl alcohol gel solution containing bone growth promoting factor BMP-2 and antibacterial peptide are 180 μ g/ml and 360 μ g/ml, respectively.
5. The method for preparing a scaffold for biomimetic bone tissue engineering according to claim 1, comprising the steps of: (1) sequentially adding poly (caprolactone-co-lactide), tussah silk fibroin and hydroxyapatite into trifluoroethanol according to a mass ratio, uniformly mixing to form slurry, carrying out 3D printing, and then carrying out freeze drying treatment on the printed scaffold for more than 12 hours to obtain a matrix; (2) putting the substrate into a dopamine Tris-HCl solution for reaction to obtain a dopamine-modified substrate; uniformly dispersing the I-type collagen short fibers in an aqueous solution of sodium alginate, soaking the dopamine-modified substrate in an aqueous solution of I-type collagen fibers and sodium alginate, taking out, and carrying out freeze drying treatment for 4-8 hours to form a bionic layer outside the substrate, thereby obtaining a substrate scaffold with the bionic layer; (3) immersing the substrate bracket with the bionic layer in chitosan/polyvinyl alcohol mixed gel liquid containing BMP-2 and antibacterial peptide by a physical solution method under a negative pressure environment, standing for 12-24h at 4 ℃, and then placing the substrate bracket in an incubator at 37 ℃ to form gel, thereby obtaining the bionic bone tissue engineering bracket;
wherein the pH value of the dopamine Tris-HCl solution in the step (2) is 7.5-8.5, the concentration is 0.5-1.5 wt%, and the reaction time is 2-24 h.
6. The method for preparing a bionic bone tissue engineering scaffold according to claim 5, wherein the 3D printing method in the step (1) comprises the following steps: obtaining a three-dimensional model of the bone defect through a three-dimensional reconstruction technology according to the acquired CT scanning tomographic data of the autologous bone to be repaired; and then, printing the composite slurry into a required shape according to the three-dimensional model, and carrying out freeze-drying treatment on the printed scaffold for more than 12 hours to obtain the matrix of the bone tissue engineering scaffold.
7. The method for preparing a scaffolds for bionic bone tissue engineering according to claim 6, wherein the extrusion speed is 0.008mm/s and the XY stage movement speed is 2.5mm/s during 3D printing.
8. The method of claim 5, wherein the type I collagen short fiber in step (2) is prepared by adding type I collagen into 0.5-2mol/L acetic acid solution, stirring until the type I collagen is completely dissolved, debubbling to obtain a spinning dope, wherein the concentration of collagen in the spinning dope is 3-5 wt%, forming type I collagen fiber by electrospinning, and cutting to obtain type I collagen short fiber; the length of the type I collagen short fiber is 0.1mm-2 mm.
9. The method for preparing a scaffolds for bionic bone tissue engineering according to claim 5, wherein the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and antibacterial peptide in step (3) is prepared by: 1) mixing NaHCO3 solution with the concentration of 0.5-0.6mol/L and polyvinyl alcohol solution with the concentration of 0.5-3 wt%, taking a certain amount of chitosan hydrochloric acid solution with the concentration of 1.5-2.5%, placing for 15min in ice bath, slowly dropwise adding mixed solution of NaHCO3 and polyvinyl alcohol into the chitosan hydrochloric acid solution under ice bath and magnetic stirring, directly adding BMP-2 and antibacterial peptide into the mixed solution after dropwise adding, and continuously stirring until uniform mixing is achieved, thus obtaining the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and antibacterial peptide.
10. The method of claim 5, wherein in the step (3), the substrate scaffold having the biomimetic layer is immersed in the chitosan/polyvinyl alcohol mixed gel solution containing BMP-2 and antibacterial peptide by a physical solution method under negative pressure, left to stand at 4 ℃ for 12-24 hours, and then placed in an incubator at 37 ℃ for 2-24 hours to form a gel.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115581805A (en) * | 2022-10-13 | 2023-01-10 | 苏州大学附属第一医院 | Preparation method of dam-like two-phase bionic periosteum for promoting bone regeneration |
| CN116102637A (en) * | 2022-09-26 | 2023-05-12 | 西北大学 | Stable I-type recombinant collagen and application thereof |
| CN116392639A (en) * | 2023-02-17 | 2023-07-07 | 无锡市中医医院 | Full-layer repair double-layer bracket and preparation method and application thereof |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001292503A1 (en) * | 2000-10-02 | 2002-04-15 | Astrazeneca Ab | New oxabispidine compound useful in the treatment of cardiac arrhythmias |
| ITPD20030286A1 (en) * | 2003-11-27 | 2005-05-28 | Fidia Advanced Biopolymers Srl | COMPOSITE MULTISTRATE STRUCTURES CONTAINING HYALURONIC ACID |
| WO2007055431A1 (en) * | 2005-11-14 | 2007-05-18 | Seoul National University Industry Foundation | Method for producing collagen/apatite composite membrane for guided bone regeneration |
| CN102188753A (en) * | 2011-05-10 | 2011-09-21 | 中原工学院 | Nano bone biomimetic material containing tussah silk fibroin, and preparation method thereof |
| US20130218291A1 (en) * | 2012-02-21 | 2013-08-22 | Thierry Giorno | Plga/ha hydroxyapatite composite bone grafts and method of making |
| KR20140025221A (en) * | 2012-08-22 | 2014-03-04 | 가톨릭대학교 산학협력단 | Scaffolds having double layer structure with gradient mineral concentration for tissue regeneration and preparation method thereof |
| CN103990182A (en) * | 2014-05-30 | 2014-08-20 | 东华大学 | Three-dimensional scaffold material for bone tissue repair and preparation method thereof |
| CN105343936A (en) * | 2015-11-05 | 2016-02-24 | 深圳市第二人民医院 | Poly-L-lactide-caprolactone copolymer (PLCL) three-dimensional porous scaffold, PLCL and collagen (PLCL-COL) composite scaffold and preparation methods of scaffolds |
| CN105999406A (en) * | 2016-06-02 | 2016-10-12 | 温州医科大学 | Method for preparing high-efficiency antibacterial quaternary ammonium salt chitosan composite gel coating layer |
| CN107137774A (en) * | 2017-06-06 | 2017-09-08 | 上海理工大学 | A kind of fibroin albumen with three-dimensional structure/hydroxyapatite compound rest and preparation method thereof |
| CN107670115A (en) * | 2017-10-20 | 2018-02-09 | 上海纳米技术及应用国家工程研究中心有限公司 | Fibroin albumen/hydroxyapatite/poly-（Racemic lactic acid co caprolactones）The preparation method of composite nano-fiber membrane |
| CN111375088A (en) * | 2020-04-29 | 2020-07-07 | 陕西巨子生物技术有限公司 | Double-layer osteochondral tissue repair scaffold and preparation method thereof |
| CN112043871A (en) * | 2020-08-31 | 2020-12-08 | 西南交通大学 | Preparation method of bionic oriented double-layer hydrogel for bone/cartilage repair |
-
2022
- 2022-07-18 CN CN202210841681.9A patent/CN115054728B/en active Active
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001292503A1 (en) * | 2000-10-02 | 2002-04-15 | Astrazeneca Ab | New oxabispidine compound useful in the treatment of cardiac arrhythmias |
| ITPD20030286A1 (en) * | 2003-11-27 | 2005-05-28 | Fidia Advanced Biopolymers Srl | COMPOSITE MULTISTRATE STRUCTURES CONTAINING HYALURONIC ACID |
| WO2007055431A1 (en) * | 2005-11-14 | 2007-05-18 | Seoul National University Industry Foundation | Method for producing collagen/apatite composite membrane for guided bone regeneration |
| CN102188753A (en) * | 2011-05-10 | 2011-09-21 | 中原工学院 | Nano bone biomimetic material containing tussah silk fibroin, and preparation method thereof |
| US20130218291A1 (en) * | 2012-02-21 | 2013-08-22 | Thierry Giorno | Plga/ha hydroxyapatite composite bone grafts and method of making |
| KR20140025221A (en) * | 2012-08-22 | 2014-03-04 | 가톨릭대학교 산학협력단 | Scaffolds having double layer structure with gradient mineral concentration for tissue regeneration and preparation method thereof |
| CN103990182A (en) * | 2014-05-30 | 2014-08-20 | 东华大学 | Three-dimensional scaffold material for bone tissue repair and preparation method thereof |
| CN105343936A (en) * | 2015-11-05 | 2016-02-24 | 深圳市第二人民医院 | Poly-L-lactide-caprolactone copolymer (PLCL) three-dimensional porous scaffold, PLCL and collagen (PLCL-COL) composite scaffold and preparation methods of scaffolds |
| CN105999406A (en) * | 2016-06-02 | 2016-10-12 | 温州医科大学 | Method for preparing high-efficiency antibacterial quaternary ammonium salt chitosan composite gel coating layer |
| CN107137774A (en) * | 2017-06-06 | 2017-09-08 | 上海理工大学 | A kind of fibroin albumen with three-dimensional structure/hydroxyapatite compound rest and preparation method thereof |
| CN107670115A (en) * | 2017-10-20 | 2018-02-09 | 上海纳米技术及应用国家工程研究中心有限公司 | Fibroin albumen/hydroxyapatite/poly-（Racemic lactic acid co caprolactones）The preparation method of composite nano-fiber membrane |
| CN111375088A (en) * | 2020-04-29 | 2020-07-07 | 陕西巨子生物技术有限公司 | Double-layer osteochondral tissue repair scaffold and preparation method thereof |
| CN112043871A (en) * | 2020-08-31 | 2020-12-08 | 西南交通大学 | Preparation method of bionic oriented double-layer hydrogel for bone/cartilage repair |
Non-Patent Citations (1)
| Title |
|---|
| 广东省科学技术协会: "《2005广东高性能、功能材料研究与产业化及发展循环经济研讨会论文集》", 中国铁道出版社, pages: 247 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116102637A (en) * | 2022-09-26 | 2023-05-12 | 西北大学 | Stable I-type recombinant collagen and application thereof |
| CN116102637B (en) * | 2022-09-26 | 2023-09-26 | 西北大学 | Stable I-type recombinant collagen and application thereof |
| CN115581805A (en) * | 2022-10-13 | 2023-01-10 | 苏州大学附属第一医院 | Preparation method of dam-like two-phase bionic periosteum for promoting bone regeneration |
| CN116392639A (en) * | 2023-02-17 | 2023-07-07 | 无锡市中医医院 | Full-layer repair double-layer bracket and preparation method and application thereof |
| CN116392639B (en) * | 2023-02-17 | 2024-02-13 | 无锡市中医医院 | Full-layer repair double-layer bracket and preparation method and application thereof |
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