PLGA / HA stent prepared based on 3D printing technology

Abstract

The utility model discloses a PLGA / HA stent prepared based on the 3D printing technology, which comprises a stent main body, the material of the stent main body is a mixture of PLGA and HA biocompatible materials, the stent main body is provided with a plurality of through holes, the through holes are uniformly distributed regular-shaped holes, and the stent with a regular grid structure and good pore interconnection is prepared by the 3D printing technology. By means of the stent body formed by mixing PLGA with HA and other biocompatible materials, the hydrophilicity and cell adhesion of the stent are improved, meanwhile, the mechanical property of the stent is improved, and the toughness of the stent is improved; by arranging the orthohexagonal through holes, the stent with a regular grid structure and good pore interconnection is prepared through the 3D printing technology, and the mechanical property and biocompatibility of the stent are improved; a high polymer material, an extracellular matrix (ECM) simulating material and an organic material are used as the coating, so that the cell adhesion of the PLGA is further improved, and the tissue adaptability is enhanced.

Description

Technical Field

[0001] The utility model relates to the technical field of PLGA / HA scaffolds, in particular to a PLGA / HA scaffold prepared based on 3D printing technology. Background Art

[0002] PLGA / HA scaffold is a biomaterial used for bone tissue engineering, which combines the biodegradability of poly(lactic-co-glycolic acid) (PLGA) with the osteoinductivity of hydroxyapatite (HA). This scaffold has potential application value in repairing bone defects.

[0003] The patent document with Chinese patent announcement number CN210096010U has an authorization announcement date of February 21, 2020. The application discloses a bone tissue engineering scaffold, which includes a hollow grid-shaped scaffold and porous zinc-based metal balls filled therein. The porous zinc-based metal balls are solid balls with holes and grooves on the surface or fluffy balls rolled up from metal wires; support columns can also be provided in the scaffold to provide better mechanical properties; β-TCP particles can also be filled to enrich bone marrow mesenchymal stem cells. The utility model combines a grid scaffold made of titanium or zinc-based metal and its internal support columns to prepare a bone tissue engineering scaffold with excellent mechanical properties. The porous zinc-based metal balls therein can promote osteoblastic differentiation and inhibit osteoclastic differentiation. While providing support, they promote the regeneration and ingrowth of bone tissue, and then are gradually replaced by bone tissue during the degradation process. The β-TCP particles can enrich mesenchymal stem cells and promote bone repair. The utility model can be applied to large bone defects in load-bearing parts, and promotes bone tissue regeneration on the basis of providing mechanical support, thereby achieving the therapeutic effect of repairing large bone defects.

[0004] It can be seen from the above application that the hydrophobicity of existing bone tissue engineering scaffolds limits their application as cell scaffolds, resulting in poor cell adhesion; and the toughness is poor, especially in the pure form, which limits their application in bearing large mechanical loads. For this reason, a PLGA / HA scaffold prepared based on 3D printing technology is proposed. Utility Model Content

[0005] The purpose of the utility model is to provide a PLGA / HA scaffold prepared based on 3D printing technology. The scaffold body is a mixture of PLGA and other biocompatible materials such as HA, thereby improving the hydrophilicity and cell adhesion of the scaffold, while increasing its mechanical properties and improving the toughness of the scaffold. By setting the through holes as regular hexagons, 3D printing technology is used to prepare a scaffold with a regular grid structure and good pore interconnection, thereby improving the mechanical properties and biocompatibility of the scaffold. Polymer materials, materials that imitate extracellular matrix (ECM) and organic materials are used as coatings to further improve the cell adhesion of PLGA and enhance tissue adaptability.

[0006] In order to achieve the above purpose, the main technical solutions adopted by this utility model are:

[0007] A PLGA / HA scaffold prepared based on 3D printing technology includes: a scaffold body formed by printing a mixture of PLGA and HA biocompatible materials using a 3D printer, the scaffold body having a plurality of through holes, each of which is a uniformly distributed, regularly shaped hole. Under the action of the through holes, the scaffold body forms a PLGA / HA scaffold with a regular grid structure and interconnected pores.

[0008] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the through-hole is a regular hexagon.

[0009] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: end holes are opened at both ends of the scaffold body.

[0010] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the end holes are provided with at least three at each end of the scaffold body.

[0011] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the surface of the scaffold body is coated with a coating prepared by imitating extracellular matrix material.

[0012] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the scaffold body is a scaffold with gradient mechanical properties, and the surface hardness of the scaffold body is greater than its internal hardness.

[0013] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the pores of the scaffold body are coated with a platelet-rich plasma biological factor coating.

[0014] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the porosity of the scaffold body is greater than 50%, and the pore size is between 1-800 μm.

[0015] The above-mentioned PLGA / HA scaffold prepared based on 3D printing technology, wherein: the length of the scaffold body is 2-4 mm, the width is 1-3 mm, the height is 0.5-2 mm, and the layer thickness is 0.1-0.2 mm.

[0016] Compared with the prior art, the beneficial effects of the present invention are:

[0017] The PLGA / HA scaffold prepared based on 3D printing technology improves the hydrophilicity and cell adhesion of the scaffold by mixing PLGA with other biocompatible materials such as HA, while increasing its mechanical properties and improving the toughness of the scaffold. By setting the through holes as regular hexagons, 3D printing technology is used to prepare a scaffold with a regular grid structure and good pore interconnection, thereby improving the mechanical properties and biocompatibility of the scaffold. The use of polymer materials, materials that mimic the extracellular matrix (ECM), and organic materials as coatings further improves the cell adhesion of PLGA and enhances tissue adaptability. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is a schematic diagram of the main view of the PLGA / HA scaffold prepared based on 3D printing technology in the present invention;

[0019] Figure 2 This is a schematic diagram of the main cross-section of the PLGA / HA scaffold prepared based on 3D printing technology in the present invention;

[0020] Figure 3 This is a schematic cross-sectional view of the stent wall in the PLGA / HA stent prepared based on 3D printing technology in the present invention.

[0021] In the figure: 100, bracket body; 101, coating; 200, through hole; 300, end hole. DETAILED DESCRIPTION

[0022] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0023] See Figure 1-Figure 3This embodiment provides a PLGA / HA scaffold prepared based on 3D printing technology, including: a scaffold body 100. The preparation material of the scaffold body 100 is a mixture of PLGA and other biocompatible materials such as HA. This material can improve the hydrophilicity and cell adhesion of the scaffold, while increasing its mechanical properties. The scaffold body 100 is printed using a 3D bioprinter. In the PCL / PLGA / HA composite scaffold prepared by 3D printing, the addition of PCL improves the toughness of the scaffold, while the mixture of PLGA / HA improves the hydrophilicity, which is conducive to cell adhesion. The scaffold body 100 is formed by printing. 0 is a scaffold with gradient mechanical properties. The surface of the scaffold body 100 is hard and the inside is soft, which can better simulate the mechanical properties of natural bone. The scaffold is a rectangular parallelepiped with a length of 2-4 mm, a width of 1-3 mm, a height of 0.5-2 mm, a layer thickness of 0.1-0.2 mm, a printing speed of 3D printer is 3.3 mm / s, a fiber spacing of 0.5 mm, and a fiber diameter of 0.15 mm. The scaffold body 100 has a plurality of through holes 200. The through holes 200 are evenly distributed regular-shaped holes. The through holes 200 are regular hexagons and are made using 3D printing technology. A scaffold with a regular grid structure and good pore interconnection is prepared to improve the mechanical properties and biocompatibility of the scaffold. End holes 300 are provided at both ends of the scaffold body 100, and at least three end holes 300 are provided at each end. The surface of the scaffold body 100 is coated with a coating 101. The coating uses polymer materials, imitation extracellular matrix (ECM) materials and organic materials as coatings to improve the cell adhesion of PLGA and enhance tissue adaptability. By changing the composition ratio of PLGA, the mechanical properties and degradation rate of the scaffold are adjusted to better meet the needs of bone tissue engineering. With the increase of , the mechanical strength of the scaffold increases and the degradation rate decreases, but the changes are not linear. The scaffold with a ratio of 70:30 has the highest tensile strength, while the degradation rates of the scaffolds with ratios of 70:30 and 80:20 have no significant difference; the PLGA / HA nanofiber matrix is ​​prepared by electrospinning technology to improve the hydrophilicity, protein adsorption rate and mechanical properties of the scaffold, thereby improving the mechanical strength and toughness of the scaffold; the scaffold body 100 uses bioactive materials, and the bioactive materials are bioglass or calcium phosphate coatings, which can not only improve the bone integration of the scaffold, but also improve its mechanical properties.

[0024] The extracellular matrix (ECM) is a complex network of various macromolecules surrounding cells in multicellular organisms. It is primarily composed of five types of substances: collagen, non-collagenous proteins, elastin, proteoglycans, and aminoglycans. Together, these components provide support, protection, nutrition, and signaling for cells. The ECM plays an important role in maintaining tissue structure and function and is a key factor in tissue regeneration and repair.

[0025] The pores of the stent body 100 are coated with a platelet-rich plasma biological factor coating, and the growth factors in the platelet-rich plasma can be effectively activated and released, which can promote the growth and differentiation of cells on the stent surface and in the pores.

[0026] The porosity of the stent body 100 is greater than 50%, and the pore size is between 1-800 μm, so that the PLGA / HA stent has an excellent pore structure and biocompatibility, and can better support cell growth and differentiation.

[0027] In this embodiment, the PLGA / HA scaffold is combined with biological factors such as PRP to achieve the best bone healing effect.

[0028] Scaffold preparation

[0029] (1) Raw material selection: Polylactic acid-glycolic acid copolymer (PLGA) and hydroxyapatite (HA) powder with good biocompatibility are selected as the main raw materials of the scaffold.

[0030] (2) 3D printing: Using a 3D bioprinter and direct ink writing (DIW) technology, PLGA and HA powders are dispersed in an organic solvent as ink to quickly print a PLGA / HA scaffold with a porous structure. During the printing process, the ink formula and printing parameters are adjusted to achieve uniform distribution and interconnectedness of the pores within the scaffold.

[0031] The specific printing method is as follows:

[0032] Step 1. Construction of 3D printing model

[0033] A scaffold model (cuboid, 3 mm in length, 2 mm in width, and 1 mm in height) for rat tibial defects was constructed using 3D Max software and exported as an STL file. The STL file was imported into IdaeMaker software to generate slices, with settings for a layer thickness of 0.15 mm, a print speed of 3.3 mm / s, a fiber spacing of 0.5 mm, and a fiber diameter of 0.15 mm. The slices were then exported as GCode files for subsequent 3D printing.

[0034] Step 2. Preparation of HA / PLGA printing materials

[0035] Grind the HA powder in advance and pass it through a 400-mesh sieve. Add a certain amount of PLGA to dichloromethane and stir to dissolve, where the PLGA concentration is 10wt%. After the PLGA is completely dissolved, disperse the sieved HA powder in the PLGA solution (PLGA:HA mass ratio is 3:1) and stir the solution to evenly distribute the HA particles. Pour the prepared solution into a glass culture dish and let it stand in a fume hood overnight to allow the dichloromethane to completely evaporate, resulting in a HA / PLGA film. Cut the film into small pieces and store sealed in a refrigerator at 4°C.

[0036] Step 3. 3D printing of HA / PLGA composite scaffold

[0037] Load the HA / PLGA printing material into the barrel and set the temperature to 130°C for 30 minutes to allow the material to completely melt. Set the base temperature to 60°C and extrude the material layer by layer onto the base through a 27G stainless steel needle at 3-4 bar pressure to produce a 3D-printed HA / PLGA composite scaffold. Store the scaffold in a sealed container at 4°C.

[0038] (3) Post-processing: The printed stents are cleaned, dried, and disinfected to ensure the purity and sterility of the stents.

[0039] Combined platelet-rich plasma

[0040] (1) PRP preparation: Platelet-rich plasma (PRP) is obtained by centrifuging whole blood, and an appropriate amount of thrombin and catalysts such as calcium chloride are added to it to form a colloid or gel.

[0041] (2) Binding method: The prepared PRP is evenly coated on the surface and pores of the PLGA / HA scaffold. The PRP is firmly bound to the scaffold through physical adsorption or chemical cross-linking. At the same time, the growth factor activation effect of the PRP is utilized to further promote the growth and differentiation of cells on the scaffold surface and in the pores.

[0042] Application of stents

[0043] The PLGA / HA scaffold combined with PRP is implanted into the bone defect site, which promotes the regeneration and repair of bone tissue through the support of the scaffold, the biodegradability and osteoconductivity of the PLGA / HA material, and the repair-promoting effect of the growth factors in PRP.

[0044] The PLGA / HA scaffold of the present application has excellent pore structure and biocompatibility, and can better support cell growth and differentiation.

[0045] After combining with biological factors such as platelet-rich plasma (PRP), the scaffold can release a large amount of growth factors, significantly promoting the regeneration and repair of bone tissue.

[0046] The scaffold preparation method of the present application is simple, low-cost, and easy to customize, and has broad application prospects and market value.

[0047] Structural principle:

[0048] like Figure 1-Figure 3 As shown, a 3D-printed scaffold 100 with 200 regular hexagonal through-holes and well-interconnected pores is prepared using a mixture of PLGA and HA biocompatible materials. Polymer materials, extracellular matrix (ECM)-mimicking materials, and organic materials are used as surface coatings for the scaffold 100. During 3D printing, the HA / PLGA printing material is loaded into the barrel, set to 130°C, and maintained for 30 minutes to allow the material to completely melt. The base temperature is set to 60°C, and the material is extruded layer by layer onto the base through a 27G stainless steel needle at a pressure of 3-4 bar to produce the 3D-printed HA / PLGA composite scaffold, which is then sealed and stored in a refrigerator at 4°C.

[0049] In summary, the PLGA / HA scaffold prepared based on 3D printing technology improves the hydrophilicity and cell adhesion of the scaffold through the scaffold body 100 mixed with PLGA and other biocompatible materials such as HA, while increasing its mechanical properties and improving the toughness of the scaffold; by setting the through holes 200 as regular hexagons, 3D printing technology is used to prepare a scaffold with a regular grid structure and good pore interconnection, thereby improving the mechanical properties and biocompatibility of the scaffold; using polymer materials, mimicking extracellular matrix (ECM) materials and organic materials as coatings, the cell adhesion of PLGA is further improved and the tissue adaptability is enhanced.

[0050] Any portion not described in the present invention is the same as the prior art or can be implemented using the prior art. Although the embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A PLGA / HA scaffold prepared based on 3D printing technology, characterized in that: include: A stent body (100) is formed by printing a mixture of PLGA and HA biocompatible materials using a 3D printer. The stent body (100) has a plurality of through holes (200), and the through holes (200) are evenly distributed holes of regular shape. Under the action of the through holes (200), the stent body (100) forms a PLGA / HA stent with a regular grid structure and interconnected pores.

2. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 1, characterized in that: The through hole (200) is a regular hexagon.

3. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 1, characterized in that: End holes (300) are provided at both ends of the bracket body (100).

4. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 3, characterized in that: At least three end holes (300) are provided at each end of the bracket body (100).

5. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 4, characterized in that: The surface of the stent body (100) is coated with a coating (101) made of a material that mimics the extracellular matrix.

6. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 5, characterized in that: The stent body (100) is a stent with gradient-varying mechanical properties.

7. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 6, characterized in that: The surface hardness of the bracket body (100) is greater than the internal hardness thereof.

8. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 7, characterized in that: The pores of the stent body (100) are coated with a platelet-rich plasma biological factor coating.

9. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 8, characterized in that: The porosity of the stent body (100) is greater than 50%, and the pore size is between 1-800 μm.

10. The PLGA / HA scaffold prepared based on 3D printing technology according to claim 9, characterized in that: The stent body (100) has a length of 2-4 mm, a width of 1-3 mm, a height of 0.5-2 mm, and a layer thickness of 0.1-0.2 mm.

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