Preparation method of composite alveolar bone repair scaffold

Abstract

The invention discloses a preparation method of a composite alveolar bone repair stent. The method comprises the following steps: mixing nano-scale hydroxyapatite powder and medical-grade PLA plastic powder according to a mass ratio of 10-20%: 1, melting and drawing wires to obtain a PLA / HAP wire for 3D printing, setting 3D printing parameters, introducing a bone repair scaffold three-dimensional model, starting printing to obtain a PLA / HAP composite material bone repair scaffold, soaking the scaffold in a 1-3mg / mL BMP bone morphological protein solution, and carrying out 3D printing to obtain the bone repair scaffold with the PLA / HAP composite material bone morphological protein / PLA / HAP composite material bone morphological protein / PLA / HAP composite material bone morphological protein / PLA / HAP composite material bone morphological protein composite material. The BMP-PLA / HAP composite material bone repair scaffold is obtained. The hydroxyapatite / PLA composite material prepared by adopting a 3D printing technology, taking the nano-scale hydroxyapatite powder and the medical-grade PLA plastic powder as raw materials and loading the BMP bone growth factor with high biological inductivity has high strength, high hardness and impact resistance, and can be used for preparing the medical-grade hydroxyapatite / PLA composite material. The invention aims to provide a safer and more effective bone graft material for clinically repairing alveolar bone defects.

Description

Technical Field

[0001] The invention relates to the technical field of bionic materials, and in particular to a method for preparing a polylactic acid / nano hydroxyapatite composite material alveolar bone repair scaffold loaded with a bone morphological protein (BMP) drug. Background Art

[0002] Alveolar bone defect is a common symptom of bone defect in clinical practice. Alveolar bone defect refers to the loss of tissue in the area of ​​the upper and lower jaws surrounding the teeth. Once the alveolar bone defect is formed, it cannot be repaired by the patient alone. For bone defects in dentistry, traditional treatments include autologous bone transplantation, distraction osteogenesis, guided tissue regeneration, etc. Autologous bone transplantation is the gold standard for repairing large bone defects. However, surgical transplantation will cause new wounds at the donor site, leading to secondary trauma and patient pain. Rejection and secondary infection in allogeneic transplantation can lead to bone transplant failure. Artificial bone transplant materials (such as metal alloys and polymers) are not completely satisfactory in terms of biocompatibility, infection risk, rejection, and biological or mechanical properties.

[0003] In recent years, material repair and filling technology has been used for alveolar bone defects. For example, the alveolar bone repair material described in Chinese patent CN107469151B is a powdered, granular or block-shaped composite material formed by bone powder, metal salts and amino sugars, which can promote bone defect repair. However, the material is a mixture of various materials and has poor strength and cannot support the biomechanical use of alveolar bone. Patent CN114028616A discloses a method for preparing tissue engineering materials for alveolar bone defect repair, which can reduce surgical trauma, avoid immune rejection, and improve the adaptability of patients after transplantation, thereby providing a new comprehensive treatment strategy for clinical alveolar bone defect repair. However, this patent also has problems such as poor biomechanics, high production costs, and long repair time. Invention patent CN104587529A relates to a method for preparing alveolar bone repair materials, which cuts the cancellous bone of the mammalian spine and femur into small pieces, boils them, dries them and performs related operations, and uses materials such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). This method not only overcomes the shortcomings of HA being too stable and β-TCP degrading too quickly, but also adjusts the degradation rate of the material through the ratio between the two, so that its degradation rate matches the growth rate of the surrounding bone tissue, and has a significant effect of promoting bone healing; and it has a certain hardness and strength, is easy to plasticize and has abundant sources, which solves the production difficulties of artificial synthetic materials in terms of porosity, pore traffic, pore size, etc. However, this patent uses animal-derived bones, which have problems such as immune rejection and biocompatibility. Invention patent CN105497981A discloses an alveolar bone repair method based on three-dimensional printing technology. This method analyzes and locates the defective alveolar bone based on the medical imaging data of patients with moderate to severe alveolar bone defects caused by chronic periodontitis before surgery, determines the shape and size of the defective alveolar bone, establishes a three-dimensional model, selects biocompatible materials that are degradable and can induce bone regeneration, and uses biological three-dimensional printing technology to print the defective alveolar bone model. This method reduces the miscalculation of the amount of bone powder added by human factors by accurately measuring the size and volume of the alveolar bone repair module; the change in the molding properties of the bone powder particles enables the bone defect repair morphology made by the implant to not only effectively fill the bone defect, but also steadily increase the vertical height of the bone regeneration material accumulation, repair part of the horizontal alveolar bone absorption, and increase the amount of alveolar bone regeneration; using rapid prototyping technology, the alveolar bone repair module required by different patients can be formed, the internal porosity is adjustable, and the molding efficiency is high. However, this patent has the problem of poor powder bonding, as well as poor biomechanical strength and poor biological activity.

[0004] In summary, the current technical solutions mostly have problems such as insufficient mechanical properties, high cost, long repair cycle and biological rejection, making it difficult to properly solve the problem of alveolar bone repair. Summary of the invention

[0005] In order to provide a new material with excellent biomechanical properties, good immune rejection performance, and safe and effective repair of alveolar bone defects, the present invention proposes a method for preparing a composite material alveolar bone repair scaffold. Technical Solution

[0006] A method for preparing a composite material alveolar bone repair scaffold comprises the following steps: S1. Mixing nano-hydroxyapatite powder and medical-grade PLA plastic powder in a mass ratio of 10% to 20%:1, melting and drawing, and obtaining PLA / HAP filament for 3D printing; S2. Setting 3D printing parameters in the 3D printer, importing the three-dimensional model of the bone repair scaffold and starting printing to obtain a PLA / HAP composite bone repair scaffold; S3. Soak the PLA / HAP composite bone repair scaffold printed in step S2 in a 1-3 mg / mL BMP solution to obtain a BMP-PLA / HAP composite bone repair scaffold.

[0007] Furthermore, the nano-hydroxyapatite powder and the medical-grade PLA plastic powder are both sieved through a 200-mesh sieve.

[0008] Furthermore, bone morphogenic proteins include BMP4, BMP7 and BMP9.

[0009] Bone morphogenetic proteins (BMPs) belong to the TGF-β superfamily. Studies have shown that BMPs are not general growth factors, but a class of multifunctional cell differentiation factors. BMP4 is an important member of the bone morphogenetic protein family. It plays a very important role in embryonic development and the formation of various tissues and organs. It can induce bone development and differentiation of hematopoietic tissues, and can induce ectopic bone formation. BMP4, 7 and 9 all have strong osteoinductive activity. BMP plays a role in bone and cartilage development, tendon and ligament biology, adult bone homeostasis and fracture healing, cleft palate, fibrodysplasia ossificans progressiva (FOP), osteogenesis imperfecta OI, osteoarthritis and other bone-related pathologies. Beneficial Effects

[0010] The present invention adopts 3D printing technology, uses nano-hydroxyapatite powder and medical-grade PLA plastic powder as raw materials, and loads BMP bone growth factor with high bioinductivity. The prepared composite material has biomechanical properties such as high strength, high hardness and impact resistance, excellent immune rejection performance, and safer and more reliable clinical performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0011] Figure 1 It is a logic flow chart of the present invention.

[0012] Figure 2 This is an image of an X-ray examination performed after surgery in an embodiment of the present invention.

[0013] Figure 3 This is a statistical chart of bone density detected 1 month and 2 months after surgery in an embodiment of the present invention. DETAILED DESCRIPTION

[0014] In order to enable those skilled in the art to better understand the content of the present invention, the present invention is further described in conjunction with the accompanying drawings and specific implementation methods. Example

[0015] The first step is to prepare the composite material alveolar bone repair scaffold disclosed in the present invention, which specifically includes the following three steps.

[0016] S1. Mix nano-hydroxyapatite powder and medical-grade PLA plastic powder in a mass ratio of 1:5, melt and draw, and both the nano-hydroxyapatite powder and medical-grade PLA plastic powder are sieved through a 200-mesh sieve to obtain PLA / HAP filament for 3D printing; S2. Setting 3D printing parameters in the 3D printer, importing the three-dimensional model of the bone repair scaffold and starting printing to obtain a PLA / HAP composite bone repair scaffold; S3. The PLA / HAP composite bone repair scaffold printed in step S2 is immersed in a 3 mg / mL BMP solution, wherein the bone morphological proteins include BMP4, BMP7 and BMP9, to obtain a BMP-PLA / HAP composite bone repair scaffold.

[0017] In the second stage, a live pig was selected as the experimental pig. The experimental pig was fasted and deprived of water for 24 hours before the operation. General anesthesia was given by intravenous injection. The injection dose was 30 mg / kg of 3% sodium pentobarbital. A trapezoidal incision was made on the buccal gingiva of the extraction area, and then the flap was turned. The buccal cortical bone of the alveolar bone around the extraction socket was removed, and the lingual cortical bone was completely retained to form a box-shaped hole to prevent the displacement and loss of the implant material. A hole of about 3×3×3mm was established, and the implant material disinfected with ethylene oxide was placed in it as the experimental group. During the implantation, the bracket was clamped with tweezers and carefully pushed into the alveolar socket to ensure that the bracket could completely fill the alveolar socket. The wound was sutured and the wound was checked again after the operation to see if it was firmly sutured. The other side was selected to create only a bone defect without placing a bracket as the control group. Minimally invasive tooth extraction instruments were used during the tooth extraction process to reduce damage to the extraction socket. Amoxicillin was continued to be used for 2 days after the operation for continuous anti-inflammatory treatment.

[0018] The third step is to perform an X-ray examination after the operation to check the implantation condition.

[0019] In the fourth step, the bone density of the experimental group and the control group was tested one month and two months after surgery respectively.

[0020] Traditional animal models of periodontal bone defects are mainly established in small and medium-sized animals such as dogs and rabbits. However, the overall similarity between these animals and humans is low, which affects the validity and reliability of the results. In this study, pigs were selected as experimental animals. Not only are their species closer to humans, but the anatomical and functional status of their periodontal system is also similar to that of humans.

[0021] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a composite material alveolar bone repair scaffold, characterized in that: The following steps are involved: S1. Mixing nano-hydroxyapatite powder and medical-grade PLA plastic powder in a mass ratio of 10% to 20%:1, melting and drawing, and obtaining PLA / HAP filament for 3D printing; S2. Setting 3D printing parameters in the 3D printer, importing the three-dimensional model of the bone repair scaffold and starting printing to obtain a PLA / HAP composite bone repair scaffold; S3. Soak the PLA / HAP composite bone repair scaffold printed in step S2 in a 1-3 mg / mL BMP solution to obtain a BMP-PLA / HAP composite bone repair scaffold.

2. The method for preparing a composite material alveolar bone repair scaffold according to claim 1, characterized in that: The nanometer-grade hydroxyapatite powder and the medical-grade PLA plastic powder are both sieved through a 200-mesh sieve.

3. The method for preparing a composite material alveolar bone repair scaffold according to claim 1, characterized in that: The bone morphological proteins include BMP4, BMP7 and BMP9.

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