Antioxidant degradable 3D printing scaffold and preparation method thereof

Abstract

The application discloses an antioxidant degradable 3D printing support and a preparation method thereof, and belongs to the technical field of bone defect repair. The application provides a PLGA / HA / MnO2 ternary composite 3D printing biological ink, wherein the introduction of MnO2 nanoparticles endows the ink with excellent printability, mechanical support, biological activity and immune regulation function. In terms of the structure of the prosthesis, the application relates to a degradable defect bone prosthesis with a shell-mesh composite structure, wherein the outer surface is a dense solid shell (thickness 0.2-0.5 mm) for providing early mechanical support and blocking soft tissue growth, and the inner part is a mesh structure (pore unit area 4-6 mm2, porosity 45-55%) for guiding new bone growth and bone integration. Through the synergistic design of the material and the structure, the application realizes early mechanical stability, mid-term bone regeneration and long-term functional reconstruction of the defect bone repair, is suitable for various defect bone types such as the skull, the mandible, the long bone of the limbs and the like, and has a good clinical application prospect.

Description

Technical Field

[0001] This invention belongs to the field of bone defect technology, and specifically relates to a 3D printing method for bone defect repair. Background Technology

[0002] Bone defects are often caused by trauma, tumor resection, or congenital malformations. Currently, 3D printing methods for bone defect repair have shortcomings in terms of materials and modeling.

[0003] Traditional repair materials such as titanium alloys and polyetheretherketone (PEEK) suffer from problems such as mismatched elastic modulus, lack of bioactivity, and non-degradability, which can easily lead to stress shielding, infection, or removal by secondary surgery. In recent years, composite scaffolds based on hydroxyapatite (HA) and polylactic-co-glycolic acid copolymer (PLGA) have attracted attention due to their good biocompatibility and osteoconductivity. However, existing 3D printing inks generally have the following shortcomings: (1) it is difficult to balance printing accuracy and mechanical strength; (2) they lack antioxidant and anti-inflammatory functions, which is not conducive to the regulation of the postoperative microenvironment; (3) the degradation rate is not synchronized with new bone formation. Manganese dioxide (MnO2) nanomaterials have the potential to scavenge reactive oxygen species (ROS), regulate inflammatory responses, and promote osteogenic differentiation, but there are no reports of combining them with the PLGA / HA system for use in bone repair 3D printing inks.

[0004] In terms of bone defect repair modeling technology, existing technologies have involved biodegradable mandibular prostheses with pure porous mesh structures, which aim to guide new bone ingrowth into the pores and ultimately achieve bone regeneration. However, biodegradable mandibular prostheses with pure mesh structures have the following significant problems when applied in the load-bearing environment of the mandible: (1) Insufficient mechanical properties. The overall stiffness of the pure mesh structure is low, and it is prone to excessive deformation or even collapse before the bone ingrowth is completed, which cannot maintain the continuity and arc contour of the mandible; in particular, the strength of PLGA decays rapidly in the early stage of degradation, and the prosthesis is more prone to deformation, resulting in the healing of new bone in non-anatomical positions, causing facial deformities and malocclusion. (2) Soft tissue ingrowth occupies the bone regeneration space. The surface of the pure mesh is completely open, and soft tissue occupies the pores first. By the time the new bone grows, the pores have been filled by fibrous tissue, forming fibrous wrapping rather than bone integration, and the prosthesis cannot achieve firm biological fixation. (3) Explosive release of degradation acid products. The large specific surface area of ​​the pure granular network causes the lactic acid and glycolic acid produced by PLGA degradation to be released in a short period of time. Even with HA neutralization, it is still easy to form a local acidic microenvironment, which activates osteoclasts and triggers bone resorption and aseptic inflammation. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide a 3D printing method for repairing bone defects.

[0006] The technical solution of the present invention is as follows:

[0007] The preparation of 3D printing bio-ink involves introducing MnO2 nanoparticles into the PLGA / HA system to construct a composite ink with excellent printability, mechanical support, bioactivity, and immunomodulatory functions, which can be used to prepare personalized bone repair scaffolds.

[0008] A biodegradable bone defect repair body with a shell-mesh composite structure. The shell ensures mechanical strength and prevents soft tissue from preemptively occupying the pores, while the internal mesh structure facilitates the ingrowth of new bone. The bone defect repair model is sliced ​​and imported into a 3D printer, where the repair body is printed using composite ink.

[0009] The preparation of 3D printing bio-ink includes the following steps:

[0010] S1 uses potassium permanganate as the manganese source and adds polyallylamine hydrochloride (PAH) as a template agent to prepare manganese dioxide nanoparticles. The product is washed with deionized water to obtain a manganese dioxide nanoparticle suspension.

[0011] S2 disperses a suspension of manganese dioxide nanoparticles in ethanol and adds the plasticizer dibutyl phthalate (DBP) to obtain a composite functional solvent;

[0012] S3 Polylactic acid-glycolic acid copolymer (PLGA) particles are added to dichloromethane and stirred thoroughly to obtain a uniform slurry; then the composite functional solvent described in S2 is added and thoroughly mixed; hydroxyapatite (HA) micron powder is added and stirred thoroughly to obtain a uniform slurry; the organic solvent is appropriately evaporated to adjust the viscosity of the solution, thus obtaining 3D printing bio-ink.

[0013] Preferably, the particle size of the manganese dioxide nanoparticles in the composite functional solvent described in step S2 is 30-250 nm.

[0014] Preferably, the composite functional solvent described in step S2 is composed of ethanol, manganese dioxide nanoparticle suspension and plasticizer dibutyl phthalate (DBP) in a volume ratio of 3:3:1.

[0015] Preferably, the ratio of PLGA, HA and MnO2 is 20:70:1.

[0016] Preferably, the HA powder is spherical with a particle size of 80 μm.

[0017] A biodegradable bone defect repair body with a shell-mesh composite structure is provided. The bone defect repair body is prepared according to the above-mentioned 3D printing bio-ink preparation method for bone defect repair, and includes a main body structure of the repair body and a bone defect fixation plate.

[0018] The defect fixation plate matches the shape of the outer surface of the patient's healthy bone, thus achieving a seamless fit.

[0019] The bone defect fixation plate has multiple screw holes for fixing the prosthesis to healthy bone with screws.

[0020] The main structure of the prosthesis is integrally formed by 3D printing using the aforementioned 3D printing bio-ink. The outer surface of the main structure of the prosthesis is a dense solid shell, and the internal area enclosed by the solid shell is a grid structure.

[0021] The solid outer shell has a thickness of 0.2-0.5 mm and is used to provide early mechanical support to resist deformation under physiological loads of defects, while preventing surrounding soft tissue from growing into the prosthesis.

[0022] The mesh structure consists of multiple interconnected porous units, each with a regular polygonal cross-section and an area of ​​4-6 mm². The mesh structure accounts for 45-55% of the total volume of the prosthesis (i.e., a porosity of 45-55%). This porosity range ensures sufficient space for new bone growth while also providing the prosthesis with adequate initial compressive and flexural strength. The mesh structure guides bone cell ingrowth, migration, and proliferation, ultimately achieving osseointegration.

[0023] The beneficial effects of this invention are:

[0024] 1. Closed-loop synergistic safety and effectiveness: PLGA encapsulates HA to prevent aggregation, and the high HA content enhances the rigidity of PLGA and slows down the accumulation of its acidic degradation byproducts; the hydroxyl groups on the HA surface promote the anchoring of MnO2 nanoparticles, and MnO2 removes ROS to protect HA from oxidative degradation; MnO2 neutralizes the local acidic environment generated by PLGA degradation, inhibiting uncontrolled autocatalytic degradation; PLGA limits the burst release of MnO2, achieving long-term sustained release. The three components complement each other, meeting both short-term fixation requirements and adapting to long-term physiological changes.

[0025] 2. Reliable mechanical properties to prevent bone growth deformation: The dense shell provides high elastic modulus and bending and compressive strength, resisting physiological loads in the early stages of bone healing, preventing deformation and collapse of the prosthesis, maintaining the continuity of the defective bone, and ensuring that new bone grows in the correct anatomical position;

[0026] 3. Guiding bone regeneration and preventing soft tissue from occupying pores: The outer shell physically blocks soft tissue from growing into the interior; the internal mesh provides directional growth channels for new bone, achieving three-dimensional bone integration and avoiding fibrous encapsulation;

[0027] 4. Regulating degradation products to reduce inflammation and bone resorption: The shell has a small specific surface area and degrades more slowly, maintaining early mechanical integrity; the acidic products generated by mesh degradation are confined by the shell and neutralized by HA particles, avoiding acidic outbreaks at the bone interface and reducing the risk of inflammation and osteolysis. Attached Figure Description

[0028] Figure 1 This is a diagram showing the overall structure of the mandibular prosthesis and healthy bone.

[0029] Figure 2 This is a detailed structural diagram of the mandibular bone prosthesis.

[0030] Figure 3 This is a diagram of the internal structure of the mandibular prosthesis. Detailed Implementation

[0031] The technical solution of the present invention will be further explained and described below through specific embodiments.

[0032] Example 1:

[0033] 3D Printing Bio-Ink for Bone Defect Repair and its Preparation Method:

[0034] 100 mg potassium permanganate was dissolved in 10 mL of deionized water, and 5 mL of polyallylamine hydrochloride (PAH) was added as a template agent to prepare manganese dioxide nanoparticles. The product was washed with deionized water to obtain a manganese dioxide nanoparticle suspension, and the concentration of manganese dioxide was adjusted to 33 mg / mL.

[0035] 3 mL of manganese dioxide nanoparticle suspension (MnO2) was dispersed in 3 mL of ethanol, and 1 mL of plasticizer dibutyl phthalate (DBP) was added to obtain a composite functional solvent.

[0036] 2 g of polylactic acid-glycolic acid copolymer (PLGA) particles were added to 15 mL of dichloromethane and stirred thoroughly to obtain a uniform slurry. The aforementioned composite functional solvent was then added and thoroughly mixed. 7 g of hydroxyapatite (HA) micron powder was added and stirred thoroughly to obtain a uniform slurry. The organic solvent was then evaporated appropriately to adjust the viscosity of the solution, thus obtaining the 3D printing bio-ink. The properties of the ternary composite slurries with different formulations in Table 1 are shown in Table 1 below.

[0037] Table 1

[0038]

[0039] Example 2

[0040] Taking mandibular bone repair modeling as an example, a biodegradable mandibular bone prosthesis with a shell-mesh composite structure, such as... Figure 1 As shown, it includes the main structure of the prosthesis 1, the left mandibular fixation plate 11, and the right mandibular fixation plate 12.

[0041] like Figure 2As shown, the left mandibular fixation plate 11 and the right mandibular fixation plate 12 are respectively disposed on the left and right sides of the main structure 1 of the prosthesis. The inner surface of the left mandibular fixation plate 11 matches the shape of the outer surface of the patient's left healthy bone 2, and the inner surface of the right mandibular fixation plate 12 matches the shape of the outer surface of the patient's right healthy bone 3, thereby achieving a seamless fit. The left mandibular fixation plate 11 and the right mandibular fixation plate 12 are each provided with multiple screw holes 111 for fixing the prosthesis to the left healthy bone 2 and the right healthy bone 3 using screws.

[0042] like Figure 3 As shown, the main structure 1 of the prosthesis is integrally formed by 3D printing using biodegradable biomaterials. The outer surface of the main structure of the prosthesis is a dense solid shell 13, and the internal area enclosed by the solid shell is a mesh structure 14.

[0043] The solid outer shell 13 has a thickness of 0.2-0.5 mm and is used to provide early mechanical support to resist deformation under physiological loads on the mandible, while preventing surrounding soft tissue from growing into the prosthesis.

[0044] The mesh structure 14 is composed of multiple interconnected pore units, each pore unit having a regular polygonal cross-sectional shape and an area of ​​4-6 mm². The volume of the mesh structure accounts for 45-55% of the total volume of the main structure of the restoration (i.e., the porosity is 45-55%).

[0045] The upper surface of the main structure 1 of the prosthesis is also provided with a plurality of tooth preparation implant holes 15. The tooth preparation implant holes 15 penetrate the solid shell 13 and extend to the surface of the mesh structure 14, and the position, diameter and angle of the preparation implant holes are matched with the implantation plan of the dental implant in the later stage.

Claims

1. A method for preparing 3D printing bio-ink for bone defect repair, characterized in that: Includes the following steps: S1 uses potassium permanganate as the manganese source and adds polyallylamine hydrochloride (PAH) as a template agent to prepare manganese dioxide nanoparticles. The product is washed with deionized water to obtain a manganese dioxide nanoparticle suspension. S2 disperses a suspension of manganese dioxide nanoparticles in ethanol and adds the plasticizer dibutyl phthalate (DBP) to obtain a composite functional solvent; S3 Polylactic acid-glycolic acid copolymer (PLGA) particles are added to dichloromethane and stirred thoroughly to obtain a uniform slurry; then the composite functional solvent described in S2 is added and thoroughly mixed; hydroxyapatite (HA) powder is added and stirred thoroughly to obtain a uniform slurry; the viscosity of the solution is adjusted by evaporating the organic solvent, thus obtaining the 3D printing bio-ink.

2. The method for preparing 3D printing bio-ink for bone defect repair according to claim 1, characterized in that: The particle size of manganese dioxide nanoparticles in composite functional solvents ranges from 30 to 250 nm.

3. The method for preparing 3D printing bio-ink for bone defect repair according to claim 2, characterized in that: The composite functional solvent is composed of ethanol, manganese dioxide nanoparticle suspension and plasticizer dibutyl phthalate (DBP) in a volume ratio of 2-4 parts: 3-6 parts: 1-2 parts.

4. The method for preparing 3D printing bio-ink for bone defect repair according to claim 3, characterized in that: The ratio of PLGA, HA and MnO2 is 10-20 parts: 60-70 parts: 1-5 parts.

5. The method for preparing 3D printing bio-ink for bone defect repair according to claim 4, characterized in that: The hydroxyapatite powder is spherical with a particle size of 20μm-200μm.

6. A biodegradable bone repair body with a shell-mesh composite structure, characterized in that, The prosthesis is integrally formed by 3D printing using 3D printing bio-ink prepared by any one of claims 1-5, and includes: a main structure of the prosthesis and a bone defect fixation plate. The inner surface of the bone defect fixation plate matches the shape of the outer surface of the patient's healthy bone. The bone defect fixation plate has multiple screw holes for fixing the prosthesis to the healthy bone with screws. The outer surface of the main structure of the prosthesis is a dense solid shell, and the internal area enclosed by the solid shell is a mesh structure.

7. A biodegradable bone repair body with a shell-mesh composite structure as described in claim 6, characterized in that: The thickness of the solid outer shell is 0.2-0.5 mm.

8. A biodegradable bone repair body with a shell-mesh composite structure as described in claim 7, characterized in that: The mesh structure is composed of multiple interconnected pore units, and the cross-sectional shape of the pore unit is a regular polygon with an area of ​​4-6 mm².

9. A biodegradable bone repair body with a shell-mesh composite structure as described in claim 8, characterized in that: The volume of the mesh structure accounts for 45-55% of the total volume of the main structure of the restoration.

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