CN116942923A - Medical composite absorbable interface screw and preparation method thereof - Google Patents
Medical composite absorbable interface screw and preparation method thereof Download PDFInfo
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- CN116942923A CN116942923A CN202310934849.5A CN202310934849A CN116942923A CN 116942923 A CN116942923 A CN 116942923A CN 202310934849 A CN202310934849 A CN 202310934849A CN 116942923 A CN116942923 A CN 116942923A
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- polylactic acid
- hydroxyapatite
- interface screw
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- 238000002360 preparation method Methods 0.000 title abstract description 17
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- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims description 2
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- 102000004190 Enzymes Human genes 0.000 description 1
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- 239000000427 antigen Substances 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/028—Other inorganic materials not covered by A61L31/022 - A61L31/026
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Abstract
The invention belongs to medical implant materials, and particularly relates to a medical composite absorbable interface screw and a preparation method thereof. The interface screw is formed by mixing modified hydroxyapatite, low-molecular-weight polylactic acid and L-polylactic acid; the weight percentage of the modified hydroxyapatite is 1-50%, the weight percentage of the low molecular weight polylactic acid is 1-15%, and the weight percentage of the L-polylactic acid is 50-100%; the modified hydroxyapatite is obtained by carrying out surface chemical grafting polymerization on the hydroxyapatite by a polyester monomer composition. The modified hydroxyapatite provided by the invention realizes the self-reinforcing effect of nano hydroxyapatite in the levorotatory polylactic acid matrix, and improves the mechanical property of the material; the introduction of low molecular polylactic acid allows the degradation rate of the interface screw to be matched with the bone tissue repair rate.
Description
Technical Field
The invention belongs to medical implant materials, and particularly relates to a medical composite absorbable interface screw and a preparation method thereof.
Background
The interface screw is clinically used for transplanting and fixing bone, tendon and bone or soft tissues in the operation of reconstructing the anterior cruciate ligament and the posterior cruciate ligament of the knee ligament injury. Compared with the interface screw prepared from the traditional stainless steel and titanium alloy, the absorbable interface screw has unique biodegradability, so that the loss of human body caused by secondary operation extraction can be avoided. In addition, the absorbable interface screw also has the advantages of good biocompatibility and safety, induction of rapid bone tissue repair and the like, so that the absorbable interface screw becomes an orthopedic implant internal fixture widely used in clinic at present.
Hydroxyapatite/polylactic acid composite materials are one of the current research hotspots as the material composition of absorbable interface screws. Hydroxyapatite (HA) is a main inorganic component of human bone tissue, and calcium ions and phosphorus ions released by degradation of the HA can induce bone cells to adsorb, proliferate and grow. Polylactic acid (PLA) polymeric materials provide the mechanical strength required to maintain bone growth and are gradually degraded and absorbed by the body as the osteogenesis process proceeds. Although the existing composite material has considered to integrate the degradation performance, mechanical strength and osteoinductive performance of the composite material and improves the comprehensive performance and effect of the absorbable interface screw to a certain extent, the composite material still has some problems in practical application.
Chinese patent CN102490308A discloses a method for preparing an absorbable composite internal fixation device. The patent method adopts a mixed injection molding integrated process, and the poly-L-lactic acid and the hydroxyapatite are dried and blended to obtain a composite material, and then the composite material is molded by a micro injection machine and maintained in pressure to obtain the composite internal fixing device. Because the fusion and blending of the hydroxyapatite and the polylactic acid are extremely easy to generate the agglomeration effect of nano particles, and the high temperature of the mixing reaction (the reaction temperature disclosed by the patent is 170-250 ℃) can also cause the breakage and degradation of polylactic acid molecular chains, so that the mechanical property of an interface screw product is greatly reduced. According to the description of the examples of this patent, the internal fixation device was prepared with a maximum flexural strength of 128.43Mpa and a corresponding elastic modulus of 0.49Gpa.
Chinese patent CN101293116 discloses an absorbable bone interface screw and its preparation method. The patent method mixes the nanometer beta-tricalcium phosphate powder with polylactic acid by adopting a solution, uniformly disperses the nanometer beta-tricalcium phosphate powder in a polymer matrix by using a tape casting quick drying method, and forms the nanometer beta-tricalcium phosphate powder in an injection molding machine. Because the beta-tricalcium phosphate has very large specific surface area, not only can the degradability of the bone nail be enhanced, but also the strength of the interface screw can be increased. But the degradation rate of beta-tricalcium phosphate is very fast and is difficult to match with the rate of bone growth.
Chinese patent CN104984414a discloses a composite absorbable interface screw and method for making same. The patent prepares the composite absorbable interface screw by dissolving 70-95% of polylactic acid polymer and 5-30% of heterogeneous antigen-removed cortical bone powder into mixed solution by methylene dichloride, quick casting, drying, film forming, crushing and injection molding. However, the antigen in the heterogeneous cortical bone powder is difficult to ensure complete removal, a small amount of residue is very easy to exist, and inflammatory reaction is caused after the interfacial screw is implanted into the body. According to the description of the examples of this patent, the highest flexural strength of the interfacial screw prepared from the modified bone powder was 145Mpa.
In view of the foregoing, there is a need for new methods and strategies to ameliorate at least one of the above problems.
Disclosure of Invention
The invention aims to provide a medical composite absorbable interface screw and a preparation method thereof, and the specific technical scheme is as follows.
The medical composite absorbable interface screw is formed by mixing modified hydroxyapatite, low-molecular-weight polylactic acid and levorotatory polylactic acid; the weight percentage of the modified hydroxyapatite is 1-50%, the weight percentage of the low molecular weight polylactic acid is 1-15%, and the weight percentage of the L-polylactic acid is 50-100%; the modified hydroxyapatite is obtained by carrying out surface chemical grafting polymerization on the hydroxyapatite by a polyester monomer composition; the polyester monomer composition includes epsilon-caprolactone and lactide.
Further, the low molecular weight polylactic acid has a number average molecular weight of 500 to 5000.
Further, the weight average molecular weight of the L-polylactic acid is 30-100 ten thousand, and the intrinsic viscosity is 2.5-4.2 dL/g.
Further, the mole ratio of epsilon-caprolactone to lactide is 1:0.1 to 10.
The preparation method of the medical composite absorbable interface screw comprises the following steps:
1) Carrying out surface chemical grafting polymerization on the hydroxyapatite by the polyester monomer composition under the action of a catalyst to obtain modified hydroxyapatite, wherein the catalyst comprises at least one of stannous octoate, stannous chloride or stannous oxide;
2) Adding the modified hydroxyapatite, low molecular weight polylactic acid and levorotatory polylactic acid into chloroform for ultrasonic dispersion and stirring to form a mixed solution, and sequentially carrying out methanol sedimentation, centrifugation and drying to obtain composite material particles;
3) And adding the composite material particles into a miniature horizontal injection molding machine, melting, extruding and injection molding an interface screw blank, and performing annealing heat treatment in an oven to obtain the medical composite absorbable interface screw.
Further, the mole percentage of the catalyst is 0.001-2%; the reaction temperature of the grafting polymerization reaction is 60-180 ℃ and the reaction time is 6-24 h.
Further, the ultrasonic dispersion time in the step 2 is 2-4 hours, and the ultrasonic dispersion power is 80-560 w.
Further, the blending temperature of the mixed solution in the step 2 is 20-50 ℃, and the stirring time is 1-4 h.
Further, in the step 3, the injection temperature is 180-220 ℃, the injection pressure is 300-900 bar, the dwell time is 10-50 s, and the mold temperature is 40-100 ℃.
Further, in the step 3, the annealing heat treatment temperature is 60-180 ℃ and the annealing time is 1-10 h.
Beneficial technical effects
The invention mainly solves the problem that the mechanical strength of the absorbable interface screw is weak in the degradation process of the implanted body; the degradation rate is not matched with the bone tissue repair rate. The solution is proposed from the aspects of material composition control (polyester monomer modified hydroxyapatite) and molding process optimization (annealing treatment).
1) Firstly, carrying out surface chemical grafting modification on nano-hydroxyapatite by using a polyester monomer combination, polymerizing on the surface of the nano-hydroxyapatite to generate topological structures with different chain lengths, and combining the topological structures on the surface of the nano-hydroxyapatite by chemical covalent bonds (see fig. 3 and 4, wherein characteristic group peak C=O appears in FTIR in fig. 4), so as to obtain the nano-hydroxyapatite modified by the polyester monomer. The interfacial compatibility of the modified hydroxyapatite and the levorotatory polylactic acid and the agglomeration effect of the nano particles are improved, and the self-enhancement effect of the nano hydroxyapatite in the levorotatory polylactic acid matrix is realized.
2) And then the polylactic acid with low molecular weight is selected to effectively improve the injection molding processing fluidity of the L-polylactic acid, meanwhile, the distribution of the molecular weight of the polylactic acid is increased, and the degradation speed of the L-polylactic acid is regulated and controlled to be matched with the repairing speed of bone tissues.
3) After the injection molding of the composite material, the invention carries out annealing heat treatment to perfect the crystallization of the absorbable interface screw, thus obtaining higher initial mechanical strength, the bending strength reaches 190MPa at most, and the elastic modulus is 3.9Gpa.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below. Like elements or portions are generally identified by like reference numerals throughout the several figures. In the drawings, elements or portions thereof are not necessarily drawn to scale. It will be apparent to those of ordinary skill in the art that the drawings in the following description are of some embodiments of the invention and that other drawings may be derived from these drawings without inventive faculty.
FIG. 1 is a flow chart of a method of making a composite absorbable interface screw in accordance with the present invention;
FIG. 2 is an in vitro cytotoxicity result of the composite absorbable interface screw prepared in example 2 of the present invention;
FIG. 3 shows a modified hydroxyapatite (a represents an example of hydroxyapatite and b represents a polyester monomer) prepared by the method of the present invention;
FIG. 4 is an infrared spectrum (FTIR) diagram of hydroxyapatite and modified hydroxyapatite.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Herein, "and/or" includes any and all combinations of one or more of the associated listed items.
Herein, "plurality" means two or more, i.e., it includes two, three, four, five, etc.
It should be noted that, in this document, 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 one … …" does not exclude the presence of other like elements in a process, method, article, or apparatus that comprises the element.
As used in this specification, the term "about" is typically expressed as +/-5% of the value, more typically +/-4% of the value, more typically +/-3% of the value, more typically +/-2% of the value, even more typically +/-1% of the value, and even more typically +/-0.5% of the value.
In this specification, certain embodiments may be disclosed in a format that is within a certain range. It should be appreciated that such a description of "within a certain range" is merely for convenience and brevity and should not be construed as a inflexible limitation on the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all possible sub-ranges and individual numerical values within that range. For example, a rangeThe description of (c) should be regarded as having been specifically disclosedSub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc. are opened, as well as individual numbers within this range, such as 1,2,3,4,5, and 6. The above rule applies regardless of the breadth of the range.
The effective grafting rate of the invention refers to the mass proportion of the polyester monomer successfully grafted to the surface of the hydroxyapatite through grafting modification chemical reaction, and the effective grafting rate can be calculated by a thermogravimetric analyzer (TGA) according to different decomposition temperatures of the polyester monomer (400-500 ℃) and the hydroxyapatite (more than 1100 ℃).
Example 1
(1) Preparation of polyester monomer modified hydroxyapatite
10g of a polyester monomer combination (epsilon-caprolactone: lactide molar ratio of 1:0.1-10), 5g of hydroxyapatite (average particle diameter of 80 nm) and 0.001-2% stannous octoate catalyst were added to 500ml of a xylene solution to form a mixed solution. Under the protection of nitrogen atmosphere, the mixed solution is polymerized for 18 hours at the constant temperature of 120 ℃, a chloroform-ethanol system is selected to dissolve and ultrasonically wash the reaction product, and after centrifugal sedimentation and vacuum drying, the polyester monomer modified hydroxyapatite is obtained, and the effective grafting rate of the polyester monomer is 8 percent through a thermogravimetric Test (TGA).
(2) Preparation of composite materials
15 parts of polyester monomer modified hydroxyapatite (grafting rate 8%), 5 parts of low molecular weight polylactic acid (number average molecular weight 500-1000) and 80 parts of L-polylactic acid (weight average molecular weight 40-50 ten thousand, intrinsic viscosity 2.5-2.9 dL/g) are added into chloroform, the temperature is raised to 30 ℃, stirring and dispersing are carried out for 1-2 hours, then ultrasonic dispersing is carried out for 1 hour with 380w of power, a mixed solution is formed, and methanol sedimentation, centrifugation and vacuum drying are sequentially carried out, thus obtaining composite material particles.
(3) Forming heat treatment of absorbable interface screw
Drying the composite material particles (the water content is less than 300 ppm), adding the dried composite material particles into a miniature horizontal injection molding machine, carrying out melt extrusion injection molding on the composite material particles at the injection molding temperature interval of 180-200 ℃ under the injection molding pressure of 600bar for 20s under the pressure maintaining time of 60 ℃ and the die temperature of 60 ℃, and then carrying out annealing for 6h in a 140 ℃ oven to obtain the medical composite absorbable interface screw, wherein the crystallinity of the interface screw is 57 percent as measured by a differential thermal calorimeter (DSC).
Example 2
(1) Preparation of polyester monomer modified hydroxyapatite
10g of a polyester monomer combination (epsilon-caprolactone: lactide molar ratio of 1:0.1-10), 5g of hydroxyapatite (average particle diameter of 80 nm) and 0.001-2% stannous octoate catalyst were added to 500ml of a xylene solution to form a mixed solution. Under the protection of nitrogen atmosphere, carrying out polymerization reaction on the mixed solution at the constant temperature of 150 ℃ for 10 hours, selecting a chloroform-ethanol system to carry out dissolution ultrasonic washing on the reaction product, carrying out centrifugal sedimentation and vacuum drying, and obtaining the polyester monomer modified hydroxyapatite, wherein the effective grafting rate of the polyester monomer is 16% through a thermogravimetric Test (TGA).
(2) Preparation of composite materials
15 parts of polyester monomer modified hydroxyapatite (grafting rate 16%), 5 parts of low molecular weight polylactic acid (number average molecular weight 1000-2000) and 80 parts of L-polylactic acid (weight average molecular weight 50-80 ten thousand, intrinsic viscosity 2.8-3.1 dL/g) are added into chloroform, the temperature is raised to 30 ℃, stirring and dispersing are carried out for 1-2 hours, then ultrasonic dispersing is carried out for 1 hour with 380w of power, a mixed solution is formed, and methanol sedimentation, centrifugation and vacuum drying are sequentially carried out, thus obtaining composite material particles.
(3) Forming heat treatment of absorbable interface screw
Drying the composite material particles (the water content is less than 300 ppm), adding the dried composite material particles into a miniature horizontal injection molding machine, carrying out melt extrusion injection molding on the composite material particles at the injection molding temperature interval of 190-210 ℃, the injection molding pressure of 800bar, the dwell time of 20s and the mold temperature of 60 ℃, carrying out annealing heat treatment in an oven at 150 ℃ for 6 hours, and obtaining the medical composite absorbable interface screw, wherein the crystallinity of the interface screw is 68% measured by a differential calorimeter (DSC).
Example 3
(1) Preparation of polyester monomer modified hydroxyapatite
10g of a polyester monomer combination (epsilon-caprolactone: lactide molar ratio of 1:0.1-10), 5g of hydroxyapatite (average particle diameter of 80 nm) and 0.001-2% stannous octoate catalyst were added to 500ml of a xylene solution to form a mixed solution. Under the protection of nitrogen atmosphere, carrying out polymerization reaction on the mixed solution at the constant temperature of 150 ℃ for 6 hours, selecting a chloroform-ethanol system to carry out dissolution ultrasonic washing on the reaction product, carrying out centrifugal sedimentation and vacuum drying, and obtaining the polyester monomer modified hydroxyapatite, wherein the effective grafting rate of the polyester monomer is 10% through a thermogravimetric Test (TGA).
(2) Preparation of composite materials
15 parts of polyester monomer modified hydroxyapatite (grafting rate 10%), 5 parts of low molecular weight polylactic acid (number average molecular weight 1500-4000) and 80 parts of L-polylactic acid (weight average molecular weight 40-60 ten thousand, intrinsic viscosity 2.5-3.4 dL/g) are added into chloroform, the temperature is raised to 30 ℃, stirring and dispersing are carried out for 1-2 hours, then ultrasonic dispersing is carried out for 1 hour with 380w of power, a mixed solution is formed, and methanol sedimentation, centrifugation and vacuum drying are sequentially carried out, thus obtaining composite material particles.
(3) Forming heat treatment of absorbable interface screw
Drying the composite material particles (the water content is less than 300 ppm), adding the dried composite material particles into a miniature horizontal injection molding machine, carrying out melt extrusion injection molding on the composite material particles at the injection molding temperature interval of 180-200 ℃ under the injection molding pressure of 600bar for 20s under the pressure maintaining time of 20s under the mold temperature of 60 ℃, carrying out annealing in an oven at 150 ℃ for 4h, and obtaining the medical composite absorbable interface screw, wherein the crystallinity of the interface screw is 63% as measured by a differential calorimeter (DSC).
Example 4
(1) Preparation of polyester monomer modified hydroxyapatite
10g of a polyester monomer combination (epsilon-caprolactone: lactide molar ratio of 1:0.1-10), 5g of hydroxyapatite (average particle diameter of 80 nm) and 0.001-2% stannous octoate catalyst were added to 500ml of a xylene solution to form a mixed solution. Under the protection of nitrogen atmosphere, the mixed solution is polymerized for 6 hours at the constant temperature of 170 ℃, a chloroform-ethanol system is selected to dissolve and ultrasonically wash the reaction product, and after centrifugal sedimentation and vacuum drying, the polyester monomer modified hydroxyapatite is obtained, and the effective grafting rate of the polyester monomer is 13 percent through a thermogravimetric Test (TGA).
(2) Preparation of composite materials
15 parts of polyester monomer modified hydroxyapatite (grafting rate 13%), 5 parts of low molecular weight polylactic acid (number average molecular weight 4000-5000) and 80 parts of L-polylactic acid (weight average molecular weight 80-100 ten thousand, intrinsic viscosity 3.1-4.2 dL/g) are added into chloroform, the temperature is raised to 30 ℃, stirring and dispersing are carried out for 1-2 hours, then ultrasonic dispersing is carried out for 1 hour with 380w of power, a mixed solution is formed, and methanol sedimentation, centrifugation and vacuum drying are sequentially carried out, thus obtaining composite material particles.
(3) Forming heat treatment of absorbable interface screw
Drying the composite material particles (the water content is less than 300 ppm), adding the dried composite material particles into a miniature horizontal injection molding machine, carrying out melt extrusion injection molding on the composite material particles at the injection molding temperature interval of 180-220 ℃, the injection molding pressure of 800bar, the dwell time of 20s and the mold temperature of 60 ℃, carrying out annealing heat treatment in an oven at 170 ℃ for 2 hours, and obtaining the medical composite absorbable interface screw, wherein the crystallinity of the interface screw is 48 percent as measured by a differential calorimeter (DSC).
TABLE 1 interfacial screw prepared by the method of the present invention
Conclusion of experiment: the modified nano-hydroxyapatite is prepared successfully by regulating and controlling the conditions such as the proportion of the polyester monomer types, the reaction time, the reaction temperature and the like. Different effective grafting rate data are obtained under different preparation conditions, wherein the reaction temperature is the largest influencing factor, and the factor with the larger influence is the reaction time. The improvement of the effective grafting rate is beneficial to improving the interfacial compatibility and the binding force of the hydroxyapatite and the levorotatory polylactic acid, so that the mechanical property of the interfacial screw is improved, and the degradation property verification result is shown in the table 2. Secondly, the method also prepares the interface screw with different crystallinity through an annealing heat treatment process. The method of the invention ensures that the molecular chains are orderly and orderly stacked and arranged by adjusting proper temperature and time, and the crystal structure of the interface screw is continuously perfected. When the annealing time is the same, the temperature is increased, the molecular chain movement capability is enhanced, and the crystallinity is increased along with the temperature (examples 1 and 2); at the same annealing temperature, the molecular chain has sufficient movement time, and the crystallinity increases with the annealing time (examples 2, 3). However, when the annealing temperature is too high (example 4), the molecular chain breaks, and the interfacial screw thermally degrades, resulting in a significant decrease in crystallinity. In addition, crystallinity is related to the nature of the raw materials (molecular weight, component ratio), injection molding process (temperature, pressure, time), etc. In view of the crystallinity of the interface screw, generally, the higher the crystallinity, the higher the initial mechanical strength can be provided for the interface screw, but the higher the crystallinity at the same time means that the degradation rate is slower, so the low-molecular polylactic acid is introduced to regulate the molecular weight distribution so as to solve the problem of too slow degradation rate.
Comparative example 1
(1) Preparation of composite materials
Adding 20 parts of hydroxyapatite (average particle size of 80 nm) and 80 parts of levorotatory polylactic acid (weight average molecular weight of 50-80 ten thousand, intrinsic viscosity of 2.8-3.1 dL/g) into chloroform, heating to 30 ℃, stirring and dispersing for 1-2 h, then performing ultrasonic dispersion for 1h with 380w power to form a mixed solution, and sequentially performing methanol sedimentation, centrifugation and vacuum drying to obtain composite material particles.
(2) Forming heat treatment of absorbable interface screw
Drying the composite material particles (the water content is less than 300 ppm), adding the dried composite material particles into a miniature horizontal injection molding machine, and carrying out melt extrusion injection molding at the injection molding temperature range of 190-210 ℃, the injection molding pressure of 800bar, the dwell time of 20s and the mold temperature of 60 ℃ to obtain the medical composite absorbable interface screw, wherein the crystallinity of the interface screw is measured to be 42% by a differential thermal calorimeter (DSC).
Example 5
Simulated in vitro accelerated degradation performance of absorbable interface screw
100ml of PBS phosphate buffer solution (pH=7.40) was prepared, the prepared absorbable interface screw was put into a centrifuge tube containing 50ml of phosphate buffer solution, and the tube was placed in a shaker at 70℃for 5 test cycles of shaking for 0, 2, 4, 8 and 12 weeks, and then taken out, and evaluation results of pH, weight average molecular weight, intrinsic viscosity, mechanical strength (flexural strength and elastic modulus) were shown in Table 2.
Table 2 comparison of simulated in vitro accelerated degradation performance of absorbable interface screw samples from example 2 and comparative example 1
Conclusion of experiment: from the results of the simulated in vitro accelerated degradation performance of the absorbable interface screw in the above example 2 and comparative example 1, it can be found that the pH value of the medical composite absorbable interface screw prepared by the invention is maintained between 7.30 and 7.40 and is similar to the pH value of the blood environment of the human body along with the degradation process, which indicates that the degradation product of the interface screw can be absorbed and is not easy to cause inflammatory reaction. The introduction of the low molecular polylactic acid leads the weight average molecular weight and the molecular weight distribution of the L-polylactic acid to be obviously changed, which indicates that the degradation performance is improved. The polyester monomer is combined to modify the hydroxyapatite, so that the interface compatibility between the nano hydroxyapatite and the levorotatory polylactic acid matrix is improved, and the crystallinity of the interface screw is perfected by further annealing heat treatment, so that the initial mechanical strength is higher, wherein the bending strength reaches 190MPa, and the elastic modulus reaches 3.9GPa. And the bending strength can still be maintained to be more than 83% of the initial strength after the material is degraded for 12 weeks along with in vitro acceleration; the elastic modulus is maintained above 66% of the initial modulus, so that the bone can be effectively ensured to provide the required biomechanical strength within 3 months of rapid growth.
Example 6
Cytotoxicity test of absorbable interface screw
The absorbable interface screws of example 2 and comparative example 1 were sterilized and placed in sterile test tubes, respectively, and a 1640 medium extract was added thereto to extract at 37℃for 24 hours. 100. Mu.l of the absorbable interface screw extract (100 ul DMEM medium as a negative control) was added to a 96-well plate containing L929 cells, and cultured for 24, 48, and 72 hours, respectively, and cell activity was measured by MTT method. Absorbance (OD) values were measured at 570nm using an enzyme-labeled instrument. The relative proliferation rate (relative growth rate, RGR) =sample absorbance value/negative control absorbance value was calculated. The results are shown in FIG. 2, and the cytotoxicity test results show that the cell survival rate is more than 100% (OD > 1), the cytotoxicity is classified into 0 grade, and the cytotoxicity meets the biological evaluation requirements of GB/T16886-5 medical instruments.
The embodiments of the present invention have been described above with reference to the accompanying drawings, but the present invention is not limited to the above-described embodiments, which are merely illustrative and not restrictive, and many forms may be made by those having ordinary skill in the art without departing from the spirit of the present invention and the scope of the claims, which are to be protected by the present invention.
Claims (10)
1. The medical composite absorbable interface screw is characterized by being formed by mixing modified hydroxyapatite, low-molecular-weight polylactic acid and levorotatory polylactic acid; the weight percentage of the modified hydroxyapatite is 1-50%, the weight percentage of the low molecular weight polylactic acid is 1-15%, and the weight percentage of the L-polylactic acid is 50-100%; the modified hydroxyapatite is obtained by carrying out surface chemical grafting polymerization on the hydroxyapatite by a polyester monomer composition; the polyester monomer composition includes epsilon-caprolactone and lactide.
2. The medical composite absorbable interface screw of claim 1, wherein the low molecular weight polylactic acid has a number average molecular weight of 500 to 5000.
3. The medical composite absorbable interface screw of claim 1, wherein the l-polylactic acid has a weight average molecular weight of 30-100 ten thousand and an intrinsic viscosity of 2.5-4.2 dL/g.
4. The medical composite absorbable interface screw of claim 1, wherein the mole ratio of epsilon-caprolactone to lactide is 1:0.1 to 10.
5. The method of preparing a medical composite absorbable interface screw of any one of claims 1-4, comprising the steps of:
1) Carrying out surface chemical grafting polymerization on the hydroxyapatite by the polyester monomer composition under the action of a catalyst to obtain modified hydroxyapatite, wherein the catalyst comprises at least one of stannous octoate, stannous chloride or stannous oxide;
2) Adding the modified hydroxyapatite, low molecular weight polylactic acid and levorotatory polylactic acid into chloroform for ultrasonic dispersion and stirring to form a mixed solution, and sequentially carrying out methanol sedimentation, centrifugation and drying to obtain composite material particles;
3) And adding the composite material particles into a miniature horizontal injection molding machine, melting, extruding and injection molding an interface screw blank, and performing annealing heat treatment in an oven to obtain the medical composite absorbable interface screw.
6. The method according to claim 5, wherein the catalyst is present in an amount of 0.001 to 2 mol%; the reaction temperature of the grafting polymerization reaction is 60-180 ℃ and the reaction time is 6-24 h.
7. The method according to claim 5, wherein the time of the ultrasonic dispersion in the step 2 is 2 to 4 hours, and the ultrasonic dispersion power is 80 to 560w.
8. The method according to claim 5, wherein the blending temperature of the mixed solution in step 2 is 20 to 50℃and the stirring time is 1 to 4 hours.
9. The process according to claim 5, wherein the injection temperature in step 3 is 180 to 220 ℃, the injection pressure is 300 to 900bar, the dwell time is 10 to 50s, and the mold temperature is 40 to 100 ℃.
10. The method according to claim 5, wherein the annealing temperature in step 3 is 60 to 180℃and the annealing time is 1 to 10 hours.
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