阅读说明：本技术 聚乳酸改性β-TCP增强聚酯复合材料用于椎间融合器的制备方法及其产品 (Preparation method of polylactic acid modified β -TCP (Transmission control protocol) reinforced polyester composite material for interbody fusion cage and product thereof ) 是由 王杰林 于建树 杨迪诚 金彩虹 于 2019-10-12 设计创作，主要内容包括：本发明涉及一种聚乳酸改性β-TCP增强聚酯复合材料用于椎间融合器的制备方法。以生物可降解聚合物为基体,以生物相容性的小分子量聚乳酸接枝改性的β-TCP为增强剂和骨诱导剂,得到的复合材料通过3D打印的方式制备可降解椎间融合器。通过本发明方法制备的生物可降解复合材料与其它直接共混的复合材料相比不仅可以满足椎间融合器的基本力学性能,同时有促成骨效果。该复合材料制备的椎间融合器生物相容性好能满足临床应用的需求。(The invention relates to a preparation method of a polylactic acid modified β -TCP reinforced polyester composite material for an interbody fusion cage, which takes a biodegradable polymer as a matrix, takes biocompatible small molecular weight polylactic acid graft modified β -TCP as a reinforcing agent and an osteoinductive agent, and prepares the degradable interbody fusion cage in a 3D printing mode.)

1. A preparation method of a polylactic acid modified β -TCP reinforced polyester composite material for an interbody fusion cage is characterized in that a biodegradable polymer is used as a matrix, a biocompatible small molecular weight polylactic acid graft modified β -TCP is used as a reinforcing agent and an osteoinductive agent, and the obtained composite material is used for preparing the degradable interbody fusion cage in a 3D printing mode, and the preparation method comprises the following steps:

(1) small molecular weight polylactic acid modified nano β -TCP

Firstly weighing dried β -TCP, adding diluted phosphoric acid with the concentration of 2% under stirring to ensure that the mass ratio of β -TCP to diluted phosphoric acid is 1/1-1/5, after phosphoric acid and β -TCP are uniformly mixed into paste, continuously reacting in a small beaker at room temperature for 1-2 h, after the reaction is finished, pumping the reactant through a circulating water type vacuum pump, washing a large amount of deionized water to remove redundant phosphoric acid, drying in a vacuum drying oven at 45 ℃ for 2 days to obtain a protonated β -TCP product, wherein the mark is β -TCP⁺；

Next, the protonated β -TCP prepared above was thoroughly dispersed in a three-necked flask containing 30 to 50 mL of xylene, and then 0.001 to 0.01 mL of Sn (Oct) was added under a nitrogen atmosphere₂Fully stirring, heating to 120 ℃, adding purified lactide to ensure that the mass ratio of β -TCP to lactide is 1/1-1/5, reacting for 12-28 h at 120 ℃, and reactingAfter the reaction, the suspension was cooled to room temperature, the mixture was centrifuged at 4000rpm, and the resulting white precipitate was washed with chloroform to remove the non-grafted β -TCP⁺Finally filtering, and vacuum drying for 2 days at the temperature of 45 ℃, and marking as p β -TCP;

(2) preparation of composite material for degradable interbody fusion cage

The composite material is prepared by adopting a solution pouring method, wherein the degradable copolymer is dissolved in a dichloromethane solvent at the concentration of 5-20 w/v%, dry p β -TCP nanoparticles are added into the copolymer solution, magnetic stirring and ultrasonic treatment are carried out simultaneously, and after the mixture is uniformly mixed, the mixture is transferred into a glassware to be naturally volatilized and dried, so that the composite material for preparing the in-vitro visual degradable interbody fusion cage is obtained;

(3) 3D printing of interbody fusion cage

Cutting the composite material obtained in the step (2) into small pieces, and performing biological 3D printing on the degradable interbody fusion cage, namely melting the material into a flowable liquid state by using high temperature, extruding the flowable liquid state by using a printing head, curing the extruded material in a cold state, finally arranging the extruded material layer by layer in a three-dimensional space to form a three-dimensional object, modeling the interbody fusion cage, introducing the three-dimensional object into 3D printer software, setting printing parameters including layer height, printing interval and filament outlet rate, and setting the printing rate to be 2-10 mm/s according to the fluidity of the melted sample.

2. The method of claim 1, wherein the polylactic acid modified β -TCP reinforced polyester composite material is used for preparing an intervertebral cage, and the degradable copolymer comprises polylactic-co-glycolic acid (PLGA).

3. The method for preparing the polylactic acid modified β -TCP reinforced polyester composite material for the intervertebral fusion cage as claimed in claim 2, wherein the ratio of the two components in the PLGA is in the range of PLLA/PGA = 80/20-90/10.

4. The method for preparing the polylactic acid modified β -TCP reinforced polyester composite material for the interbody fusion cage of claim 3, wherein the PLGA has a viscosity coefficient of 1-2 dl/g.

5. The method for preparing the polylactic acid modified β -TCP reinforced polyester composite material for the interbody fusion cage as claimed in claim 1, wherein the p β -TCP nanoparticles are added in an amount of 2-10 wt%.

6. A polylactic acid modified β -TCP reinforced polyester composite material for an interbody fusion cage, which is prepared according to the method of any one of claims 1 to 5.

Technical Field

The invention relates to a preparation method of a polylactic acid modified β -TCP (transmission control protocol) reinforced polyester composite material for an interbody fusion cage and a product thereof, in particular to a degradable interbody fusion cage which really meets the requirements of a human body and is prepared by taking a biodegradable polymer as a matrix and modified β -TCP as a reinforcing agent and an osteoinductive agent.

Background

The existing intervertebral cage is mainly made of metal materials, but the stress shielding brought by the existing intervertebral cage causes delayed or even no fusion of vertebral bodies. The shortcomings of the existing fusion cage provide a chance for the development of a bioabsorbable fusion cage, lactic acid and glycolic acid exist in biochemical metabolic pathways of cells and organisms, and PLA, PGA or PLGA copolymer thereof can be degraded into natural metabolites. Based on years of research and good safety reports, both polymers have obtained the application permission of the U.S. food and drug administration (food and drug administration), thereby further promoting the commercial development and popularization and the practical clinical use thereof.

In order to fully utilize the degradable property of polylactic acid and the initial stability and the processability of the polylactic acid and overcome the side effect of the degradation product of the polylactic acid, β -TCP. β -TCP with a certain proportion can be added to have good degradation property and excellent bone conductivity and have similar calcium/phosphorus ratio compared with autologous bone and is used in bone repair and spinal fusion, an organic polymer matrix is compounded with inorganic β -TCP to form a composite material, so that the degradation property of PLA can be adjusted, the acidic product generated by PLA can be buffered, and the excellent bone conductivity can be brought into a composite with the polylactic acid.

Therefore, the biodegradable interbody fusion cage is prepared from the composite material by taking the biodegradable polymer as a matrix and the biocompatible small molecular weight polylactic acid graft modified β -TCP as a reinforcing agent and an osteoinductive agent through a 3D printing mode.

Disclosure of Invention

Aiming at the defects that the existing intervertebral fusion cage made of degradable high polymer materials has insufficient mechanical properties and is easy to degrade to cause inflammation, the invention aims to provide a preparation method of polylactic acid modified β -TCP reinforced polyester composite material for the intervertebral fusion cage.

The invention further aims to provide the polylactic acid modified β -TCP reinforced polyester composite material prepared by the method for the interbody fusion cage product.

The invention aims to realize the preparation method of the polylactic acid modified β -TCP reinforced polyester composite material for the interbody fusion cage, which is characterized in that a biodegradable polymer is used as a matrix, the biocompatible small molecular weight polylactic acid graft modified β -TCP is used as a reinforcing agent and an osteoinductive agent, and the obtained composite material is used for preparing the degradable interbody fusion cage in a 3D printing mode, and the preparation method comprises the following steps:

(1) small molecular weight polylactic acid modified nano β -TCP

Firstly weighing a certain mass of dried β -TCP, adding 2% diluted phosphoric acid under stirring to ensure that the mass ratio of β -TCP to diluted phosphoric acid is 1/1-1/5, continuously reacting in a small beaker at room temperature for 1-2 hours after phosphoric acid and β -TCP are uniformly mixed to form paste, draining the reactant by a circulating water type vacuum pump after the reaction is finished, washing a large amount of deionized water to remove redundant phosphoric acid, drying in a vacuum drying oven at 45 ℃ for 2 days, and marking the product as β -TCP⁺；

Next, the protonated β -TCP prepared above was thoroughly dispersed in a three-necked flask containing 30 to 50 mL of xylene, and then 0.001 to 0.01 mL of Sn (Oct) was added under a nitrogen atmosphere₂Is sufficientStirring, heating to 120 ℃, adding a certain amount of purified lactide to ensure that the mass ratio of β -TCP to lactide is 1/1-1/5, reacting at 120 ℃ for 12-28 h, separating the mixture in a centrifuge at the speed of 4000rpm when the suspension is cooled to room temperature after the reaction is finished, and washing the obtained white precipitate with a large amount of trichloromethane to wash off the precipitate which is not grafted to β -TCP⁺Finally filtering, and vacuum drying for 2 days at the temperature of 45 ℃, and marking as p β -TCP;

(2) preparation of composite material for degradable interbody fusion cage

The composite material is prepared by adopting a solution pouring method, and the specific flow is that the degradable copolymer is dissolved in a dichloromethane solvent at the concentration of 5-20 w/v%, dry p β -TCP nano particles are added into the copolymer solution, magnetic stirring and ultrasonic treatment are carried out simultaneously, after the mixture is uniformly mixed, the mixture is transferred into a glassware to be naturally volatilized and dried, and the material for preparing the in-vitro visual degradable interbody fusion cage is obtained;

(3) 3D printing of interbody fusion cage

Cutting the composite material obtained by drying in the step (2) into small pieces, wherein the biological 3D printing of the degradable interbody fusion cage is mainly realized by a fused deposition molding technology, namely, the material is fused into a flowable liquid state by high temperature, is extruded by a printing head and then is solidified in a cooling way, and finally is arranged layer by layer in a three-dimensional space to form a three-dimensional solid object, modeling the interbody fusion cage and guiding the three-dimensional solid object into 3D printer software, setting printing parameters including layer height, printing interval, wire outlet speed and the like, and setting the printing speed to be 2-10 mm/s according to the fluidity of the melted sample.

The invention relates to a degradable intervertebral fusion cage which is prepared by taking modified β -TCP as a reinforcing agent and an osteoinductive agent and really meets the requirements of a human body.

The degradable copolymer mainly refers to polylactic-co-glycolic acid (PLGA).

Further, the proportion range of the two components in the PLGA is PLLA/PGA = 80/20-90/10.

Preferably, the PLGA has a viscosity coefficient of 1 to 2 dl/g.

The p β -TCP nanoparticles can be added in an amount of 2-10 wt%.

The invention provides a polylactic acid modified β -TCP reinforced polyester composite material for an interbody fusion cage, which is prepared according to any one of the methods.

The key point of the method is that β -TCP nanoparticles are subjected to surface chemical modification, low molecular weight poly-L-lactic acid (PLLA) is grafted to the surface of β -TCP nanoparticles by a lactide ring-opening polymerization method, and then the interfacial compatibility of the inorganic nanoparticles in the composite material is researched.

The β -TCP nano-particles prepared by the method are uniformly dispersed in the degradable interbody fusion cage, have good interface compatibility and bone-promoting effect, and the interbody fusion cage prepared by the composite material has good biocompatibility and can meet the requirements of clinical application.

Drawings

FIG. 1 is a compressive strength curve of the modified p β -TCP reinforced PLGA composite prepared in example 1;

FIG. 2 is a compressive strength curve of the unmodified β -TCP reinforced PLGA composite prepared in example 2.

Detailed Description

The technical solution of the present invention is further described below by specific examples. The following examples are further illustrative of the present invention and do not limit the scope of the present invention.