CN113398325B - Fibrous membrane for enhancing screw stability and inducing bone regeneration and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of biological materials, and particularly relates to a fibrous membrane for enhancing screw stability and inducing bone regeneration and a preparation method thereof. A preparation method of a fiber membrane mainly comprises the steps of preparing a hollow porous, oriented and ordered-unordered fiber structure by using an electrostatic spinning technology, and fixing osteogenic induction components on the fiber by using a coaxial or self-assembly technology. The fiber prepared by the method can be in the shape of a film, a cylinder and a screw sleeve, so that the technical problems of infirm screw fixation and delayed or non-union of fracture healing in the existing orthopedic operation technology are solved. The fiber membrane can realize controllable in-vivo degradation according to the requirement, and is not required to be taken out by secondary operation.

Description

Fibrous membrane for enhancing screw stability and inducing bone regeneration and preparation method thereof

Technical Field

The invention belongs to the technical field of biological materials, and particularly relates to a fibrous membrane for enhancing screw stability and inducing bone regeneration and a preparation method thereof.

Background

The common injury of human beings during fracture refers to a disease caused by partial or complete fracture of bone due to trauma or pathology. In the current internal fixation treatment of fracture, for fracture patients, when the fracture is incised and reset in operation and the steel plate screw is internally fixed, the current clinically used screw sometimes cannot meet the requirement of fixing all fracture blocks, and in the fracture internal fixation operation process, the screw can be loosened or completely loosened due to repeated screw in-out, screw replacement or osteoporosis, so that internal fixation failure is caused to cause a series of complications, the intensity and effect of internal fixation are affected, the failure of the internal fixation operation is possibly caused, and no good solution is available at present. Inspired by the condom, if the condom is also put on the screw and then screwed into the loose duct, the stability of the screw fixation may be increased immediately.

The electrostatic spinning technology is one kind of efficient low consumption nanometer fiber preparing technology, and the principle is that high voltage static electricity is applied between the nozzle with polymer solution and the receiver to produce electric field force opposite to the surface tension force under the action of high voltage electric field to drive the solution to stretch into one Taylor cone at the end of the nozzle. The electrospun fiber has a diameter of tens of nanometers to several micrometers, a staggered grid structure on a microstructure, controllable mechanical property and high friction, and fiber arrangement with high porosity and pore diameter can simulate the structure of extracellular matrix so as to promote cell adhesion, growth and differentiation.

Poly (3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer, P34HB, has good biocompatibility, biodegradability and spinnability, and also has good mechanical properties, and the P34HB electrospun fiber material can be partially repaired in SD rat skull defects, but has poor hydrophilicity, thereby limiting the application of the polymer in biomedicine. Graphene Oxide (GO) has better mechanical strength and hydrophilicity due to special sp2 bonding and a hexagonal carbon structure, can effectively regulate and control cell behaviors, provides locating points for cells and induces bone marrow mesenchymal stem cells to undergo osteogenic differentiation, can be used as a coating material to improve the compatibility between titanium alloy internal fixation and bone tissues, and in addition, the Graphene-based material has good antibacterial performance, so that the infection risk of an internal fixation implant can be further reduced, but GO does not have spinnability, and needs to be compounded with other materials to be electrospun into nano-micron fibers to play a role. Polyethylene glycol (Polyethylene glycol, PEG) is a hydrophilic biomaterial, has good biocompatibility and spinnability and is widely applied in the field of bio-pharmaceuticals, and a composite fiber material with P34HB has been demonstrated to promote bone regeneration, and polyethylene glycol acts as a binder to form alumina powder into a solid, indicating good metal adhesion properties.

Disclosure of Invention

In order to overcome the technical problems, the invention provides a fibrous membrane for enhancing screw stability and inducing bone regeneration and a preparation method thereof. The fiber prepared by the method can be in the shape of a film, a cylinder and a screw sleeve, so that the technical problems of infirm screw fixation and delayed or non-union of fracture healing in the existing orthopedic operation technology are solved. The fiber membrane can realize controllable in-vivo degradation according to the requirement, and is not required to be taken out by secondary operation.

In order to achieve the above object, the technical scheme provided by the invention is as follows:

a method for preparing a nano/micro fiber membrane, comprising the steps of:

s1: dispersing graphene oxide in dichloromethane or hexafu isopropanol to prepare a solution, and dissolving polyhydroxyalkanoate and polyethylene glycol in the solution to obtain a solution A;

s2: taking a syringe and an injection needle, using a tinfoil paper roller as a receiver, setting positive voltage, negative voltage, temperature, pushing injection speed and receiving distance, preparing a film, drying and sterilizing.

Preferably, in step S1, the polyhydroxyalkanoate is any one of a first generation-Polyhydroxybutyrate (PHB), a second generation-hydroxybutyrate/valerate copolyester (PHBV), a third generation-hydroxybutyrate caproate copolyester (PHBHHx) or a fourth generation-poly 3-hydroxybutyrate/4-hydroxybutyrate copolymer (P34 HB).

Preferably, in step S1, the solution A contains 7% of polyhydroxyalkanoate, 5% of polyethylene glycol, and 1mg/mL graphene oxide per 10mL of dichloromethane or hexafu isopropanol.

Preferably, in step S2, the syringe has a specification of 10mL; the injection needle is a 23G injection needle.

Preferably, in the step S2, the positive voltage is 10kV, the negative voltage is 10kV, the temperature is 37 ℃, the injection speed is 0.3mm/min, and the receiving distance is 15-20cm.

Preferably, in step S2, the dried mixture is then dried in a vacuum dryer for 48 hours, and the residual organic solvent is evaporated.

The invention also aims at providing a preparation method of the hollow porous nano/micron fiber membrane, which comprises the following steps:

(1) Dispersing graphene oxide in dichloromethane or hexafu isopropanol to prepare a solution, and dissolving polyhydroxyalkanoate and polyethylene glycol in the solution to obtain a solution A;

(2) Dissolving polyethylene glycol and an osteogenic active peptide or a natural small molecular compound in water to prepare a solution B;

(3) Taking a syringe, respectively loading a solution A and a solution B, using a coaxial spray head, taking the solution A as a shell layer, taking the solution B as a core layer, using a tinfoil paper roller as a receiver, setting positive voltage, negative voltage, temperature and pushing speed, respectively, receiving distance, preparing a fiber film, placing the fiber film in an aqueous solution, carrying out ultrasonic vibration to obtain a micrometer fiber film with a hollow porous structure, and carrying out vacuum drying and sterilization.

Another object of the present invention is to provide a method for preparing an ordered-disordered hollow porous nano/micro fiber film, characterized by comprising the steps of:

(1) Dispersing graphene oxide in dichloromethane or hexafu isopropanol to prepare a solution, and dissolving polyhydroxyalkanoate and polyethylene glycol in the solution to obtain a solution A;

(2) Dissolving polyethylene glycol in water to obtain solution B;

(3) Taking a syringe, respectively loading a solution A and a solution B, using a coaxial spray head, taking the solution A as a shell layer, taking the solution B as a core layer, using a high-speed orientation device as a receiver, setting positive voltage, negative voltage, temperature and pushing speed, respectively, receiving distance, preparing a fiber film, placing the fiber film in an aqueous solution, carrying out ultrasonic vibration to obtain a nano/micro fiber film with an ordered-disordered hollow porous structure, repeatedly soaking the fiber film in a solution with an osteogenic active peptide or a natural micromolecular compound, and carrying out vacuum drying and sterilization.

Preferably, in step (3), the osteogenic active peptide or natural small molecule compound comprises: arg-Gly-Asp (RGD) peptide, collagen mimetic peptide P-15, heparin binding peptide, bone morphogenic protein-7 derived peptide, bone morphogenic protein-2 derived peptide, glucagon-like peptide-1 (GLP-1), osteogenic growth peptide (osteogenic growth peptide, OGP), parathyroid hormone-related peptide (PTHrP-1), QK peptide, promin-1 derived peptide (Prominin-1derived peptide,PR1P); any one or more of quercetin, puerarin, resveratrol, curcumin, epigallocatechin gallate (EGCG), and berberine.

Preferably, in the step (3), the specification of the syringe is 5mL.

Preferably, in the step (3), the positive voltage is 15kV, the negative voltage is 5kV, the temperature is 37 ℃, the injection speed is 0.5/0.1mm/min, and the receiving distance is 15-20cm; the rotation speed of the receiving device is 2000r/min.

Preferably, in step (3), the dried mixture is dried in a vacuum dryer for 48 hours, and the residual organic solvent is evaporated.

Another object of the present invention is to provide a nano/micro fiber film prepared by the preparation method.

Preferably, the nano/micro fibers are in the shape of a film or hollow or solid cylinder or in the shape of a screw sleeve.

Preferably, the nano/micro fibers have a hollow porous microstructure.

It is another object of the present invention to provide a functional absorbable orthopedic screw sleeve made from the cellulose film or nano/micro fibers.

The invention also aims at providing a preparation method of the functional absorbable orthopedic screw sleeve, which comprises the following steps:

according to the diameter and length requirements of the clinical orthopaedics screw, the intelligent rolling shaft is used for making the fibrous membrane with the same thickness into sleeve shapes with different diameters and different lengths, and the fibrous membrane is integrated with the screw body.

The diameter and the length of the screw sleeve are matched with those of the clinical orthopedic screw, and the screw sleeve is tightly combined on the surface of the screw body, so that the initial stability and the anti-extraction force of the screw in operation can be effectively increased.

Preferably, the preparation of the functional absorbable orthopedic screw sleeve can also connect an orthopedic metal screw with the electrospinning receiver, and the integral structure of the screw and the screw sleeve is obtained by one-step molding.

Compared with the prior art, the invention has the technical advantages that:

(1) The fiber membrane provided by the invention is prepared by taking the biodegradable polyhydroxyalkanoate with biocompatibility and the graphene oxide as main materials through an electrostatic spinning technology. The fiber has a hollow porous or oriented structure, and the fiber membrane prepared by the method has good mechanical properties, can effectively enhance the initial stability and axial anti-extraction force of the screw after being combined with the orthopedic screw, and solves the clinical problem of screw loosening in operation.

(2) According to the invention, through the coaxial electrostatic spinning technology and combining the advantages of graphene oxide, polyhydroxyalkanoate and polyethylene glycol, a hollow porous fiber membrane with controlled slow-release components is constructed, so that the screw stability and axial anti-extraction force can be increased immediately and maintained after the screw operation, the fracture healing is promoted, and an effective solution is provided for clinical screw loosening.

(3) Simultaneously, an osteogenesis inducing component is added into the fiber with the hollow porous microstructure, so that the biological stability is improved, and the generation of new bone is induced, thereby avoiding the technical problems of weak screw fixation, delayed fracture healing, malunion or nonunion in the clinic at present; the preparation is slowly released in the bone repair process, promotes fracture healing, and has wide application prospect in the field of biological medicine, especially orthopaedics.

(4) The screw sleeve is prepared by preparing a solution of polyhydroxyalkanoate, polyethylene glycol and graphene oxide serving as bioabsorbable materials, and spinning the material into a nano-scale film, a three-dimensional sleeve shape and a screw body under a high-voltage electric field by utilizing an electrostatic spinning technology. The polyhydroxyalkanoate, polyethylene glycol and graphene oxide materials adopted are completely degradable, meanwhile, no acidic metabolite is generated, the occurrence of aseptic inflammatory reaction complications generated by the existing internal fixation materials in clinic is effectively avoided, and meanwhile, the graphene oxide has good biological activity and biomechanical property. The screw has better early biological stability, and can prevent the screw loosening problem after operation.

Further, the functional screw sleeve is prepared by adding osteogenic active peptide or natural small molecular compound into a solution of polyhydroxyalkanoate, polyethylene glycol and graphene oxide, and spinning the material into a nano-micron fiber membranous, hollow or solid cylinder shape and screw sleeve shape under a high-voltage electric field by utilizing an electrostatic spinning technology. In the material absorption process, the osteogenic active peptide or the natural small molecular compound has osteogenic induction effect, and can promote fracture healing and bone regeneration.

(5) The hollow porous fiber prepared by the invention can regulate the size of the pores on the fiber yarn so as to control the release speed of the osteogenic component.

Drawings

Fig. 1: the fibrous membrane produced in example 1;

fig. 2: an electron microscopy image of the fibrous membrane of example 1;

fig. 3: the fibrous membrane made in example 2;

fig. 4: example 2 micro pore size structure of fibrous membrane; wherein, (4-1) is a fiber hollow structure diagram; (4-2) A porous structure of the fiber surface.

Fig. 5: the fibrous membrane produced in example 3;

fig. 6: example 3 fibrous membrane fibrous arrangement microstructure; wherein, (6-1) is a fiber orientation arrangement chart; (6-2) A fiber disorder-order arrangement chart.

Fig. 7: schematic preparation of example 4; wherein 1 is solution A,2 is solution B,3 is fibrous membrane, and 4 is screw.

Fig. 8: the shape of the screw sleeve of example 4;

fig. 9: mechanical properties of the fibrous membrane of example 5; wherein a is a stress-displacement diagram; b is an elastic modulus diagram; c is an elongation diagram; d is the maximum tensile strength plot;

fig. 10: the pull-out curve versus pull-out force for example 5; a is an extraction force curve of the screw under the conditions of primary axial extraction force, secondary axial extraction force and complete looseness in an in-vitro standard test piece; b, under the condition of partial looseness, screwing each group of condom screws into an original nail channel after combining, and performing extraction force test to obtain an extraction force curve; c, under the condition of complete loosening, screwing each group of condoms into a nail channel after combining the condoms with the bolts, and performing a pull-out force test to obtain a pull-out force curve; d is the comparison of the magnitudes of the primary axial extraction force, the secondary axial extraction force and the extraction force under the condition of complete loosening in the standard test piece; e is the axial extraction force after the condoms of each group are combined with the screws under the condition of partial looseness; f is the axial extraction force after the condoms of each group are combined with the screws under the condition of complete looseness;

fig. 11: in-vitro anti-pulling test results, wherein a is a schematic operation diagram; b is a schematic diagram of the arrow nail path and the fracture line position; c is a schematic diagram of the use of a conventional set of screws; d is a schematic diagram of the use of experimental group screws; e is a schematic diagram of a non-loosening group fracture; f is a schematic diagram of the non-loosening group after healing; g is a schematic diagram of a CBCT examination result of the looseness group; h is a fracture schematic diagram of the condom group; i is a schematic diagram of a condom group after healing; j is a CBCT examination result schematic diagram of the condom group; k is a schematic diagram of a complete loosening group fracture; l is a schematic diagram after healing of the complete loosening group; m is a schematic diagram of the complete loose group CBCT examination result.

The invention will now be further described with reference to the accompanying drawings and examples:

Detailed Description

The present invention will be described by way of specific examples, to facilitate understanding and grasping of the technical solution of the present invention, but the present invention is not limited thereto. The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials, unless otherwise specified, are commercially available.

Example 1

A method of making a fibrous membrane comprising the steps of:

(1) Preparing a solution: dispersing graphene oxide in 10mL of dichloromethane for 3 hours in a dark ultrasonic manner to prepare a solution with a w/v gradient of 1mg/mL, dissolving 0.7g P34HB and 0.5g polyethylene glycol 4000 in the solution, and adding hexaflumol to 10mL to obtain a solution A (the solution A represents 10mL of hexaflumol, contains 7% P34HB,5% polyethylene glycol 4000 and 1mg/mL graphene oxide);

(2) Electrospinning: taking a 10ml syringe and a 23G syringe needle, using a tinfoil paper roller as a receiver, setting a positive voltage of about 10kV, a negative voltage of 10kV, a temperature of 37 ℃, a pushing speed of 0.3mm/min, a receiving distance of 15-20cm, and placing the obtained film in a vacuum dryer for drying for 48 hours to evaporate residual organic solvent; and (3) performing double-sided ultraviolet irradiation for 4h for sterilization to obtain a fiber membrane (a visual image is shown in figure 1), and observing the fiber structure of the fiber membrane by using a scanning electron microscope (shown in figure 2).

Example 2

A method for preparing a hollow porous fiber membrane, comprising the steps of:

(1) Preparing a solution: dispersing graphene oxide in 10mL of hexafu isopropanol for 3 hours in a dark ultrasonic manner to prepare a solution with a w/v gradient of 1mg/mL, dissolving 0.7g of P34HB and 0.5g of polyethylene glycol 4000 in the solution, adding hexafu isopropanol to 10mL to obtain a solution A, and dissolving 0.5g of polyethylene glycol 4000 and osteogenic active peptide in 10mL of water to obtain a solution B;

(2) Electrospinning: taking 2 5ml syringes to respectively load A and B solutions, using a coaxial spray head, taking the solution A as a shell layer, taking the solution B as a core layer, using a tinfoil paper roller as a receiver, setting a positive voltage of about 15kV, a negative voltage of 5kV, a temperature of 37 ℃ and a pushing speed of 0.5/0.1mm/min respectively, receiving a distance of 15-20cm, placing the obtained fiber films into an aqueous solution, fully oscillating by using an ultrasonic oscillator to obtain a micrometer fiber film with a hollow porous structure, and drying in a vacuum dryer for 48 hours to evaporate residual organic solvents; performing double-sided ultraviolet irradiation for 4h sterilization to obtain a fiber membrane (visual image is shown in figure 3), and observing the fiber structure of the fiber membrane by using a scanning electron microscope as shown in figure 4, wherein (4-1) is a fiber hollow structure diagram; (4-2) A porous structure of the fiber surface.

Example 3

A method for preparing an ordered-disordered hollow porous fibrous membrane, comprising the steps of:

(1) Preparing a solution: dispersing graphene oxide in 10mL of hexaflumol for 3 hours in a dark ultrasonic manner, preparing a solution with a w/v gradient of 1mg/mL, dissolving 0.7g P34HB and 0.5g polyethylene glycol 4000 in the solution, and adding hexaflumol to 10mL to obtain a solution A (the solution A represents that the 10mL of hexaflumol contains 7% P34HB,5% polyethylene glycol 4000 and 1mg/mL graphene oxide);

(2) Electrospinning: taking an injector to respectively load a solution A and a solution B, using a coaxial spray head, taking the solution A as a shell layer, taking the solution B as a core layer, using a high-speed orientation device as a receiver, setting a positive voltage of about 15kV, a negative voltage of 5kV, a temperature of 37 ℃ and a pushing speed of 0.5/0.1mm/min respectively, receiving the solution at a distance of 15-20cm to prepare a fiber film, placing the fiber film in an aqueous solution, carrying out ultrasonic vibration to obtain a nano/micro fiber film with an ordered-disordered hollow porous structure, repeatedly soaking the fiber film in the solution with a natural micromolecule compound, drying the fiber film in a vacuum dryer for 48 hours, irradiating two sides with ultraviolet for 4 hours for sterilization, and obtaining the fiber film (visual image is shown as figure 5), and observing the ordered-disordered fiber structure by using a scanning electron microscope, wherein (6-1) is a fiber orientation alignment chart; (6-2) A fiber disorder-order arrangement chart.

Example 4

(1) Preparing a solution: dispersing graphene oxide in 10mL of dichloromethane in a dark ultrasonic manner for 3 hours to prepare a solution with a w/v gradient of 1mg/mL, dissolving 0.7g P34HB and 0.5g polyethylene glycol 4000 in the solution, adding dichloromethane to 10mL to obtain a solution A, and dissolving 0.5g polyethylene glycol 4000 and osteogenic active peptide in 10mL of water to obtain a solution B;

(2) Preparing a screw sleeve: connecting an orthopaedics metal screw with a receiver, taking 2 5mL syringes to respectively contain A and B solutions, taking the solution A as a shell layer and the solution B as a core layer by using a coaxial spray head, setting a positive voltage of about 15kV, a negative voltage of 5kV, a temperature of 37 ℃ and a pushing speed of 0.5/0.1mm/min respectively, receiving a distance of 15-20cm, drying in a vacuum dryer for 48 hours after the screw-screw sleeve is integrated, and evaporating residual organic solvent; and (5) double-sided ultraviolet irradiation for 4 hours for sterilization. The process diagram is shown in fig. 7.

The visual diagram of the screw sleeve is shown in fig. 8, and the screw sleeve is a functional absorbable orthopedic screw sleeve and comprises a screw and a screw sleeve made of a bioabsorbable material. The screw sleeve is sleeved on the screw body part like a condom. The screw sleeve is prepared by preparing polyhydroxyalkanoate, polyethylene glycol and graphene oxide into a solution, adding osteogenic active peptide into the solution, and spinning the material into a nano-scale three-dimensional sleeve shape by using a coaxial nozzle under a high-voltage electric field by utilizing an electrostatic spinning technology. In the material absorption process, the release of the osteogenic active peptide has osteogenic induction effect, can induce the generation of new bone while increasing the biostability, and avoids the technical problems of weak screw fixation, delayed fracture healing, malunion or nonunion in the clinic at present.

Example 5

With reference to the procedure of example 1, the starting materials were used, respectively, without changing the experimental procedure: p34HB and PEG are added with graphene oxide in different proportions (0.5-2.5) to prepare a film (n=5 for each group) with the size of 10mm multiplied by 15mm multiplied by 0.14mm and the effective stretching length of 10 mm; wherein, pure P34HB is (P), the PEG is (P-P) after being added, and the graphene oxide is (P-P-G) after being added; the product is prepared: p, P-P, P-P-G0.5, P-P-G1, P-P-G1.5, P-P-G2, P-P-G2.5.

Effect evaluation:

1. mechanical property test

The experimental method comprises the following steps: the mechanical properties of the product of example 5 were tested, including stress-displacement relationship, modulus of elasticity, elongation, maximum tensile strength.

Carrying out a tensile test (100N sensor, tensile speed 1 mm/min) by a universal mechanical tester (titling science and technology Co., ltd., china); the tensile strength and Young's modulus were obtained.

As a result, as shown in fig. 9, the stress-displacement relationship of each group of film materials was measured by a mechanical tester, the average horizontal curve of each group was taken to represent each group of stress-displacement (a), the elastic modulus (b), the elongation (c), and the maximum tensile strength (d) (n=5 for each group) P < 0.05 (one-way ANOVA) (P < 0.05 "in the figure) were obtained by the mechanical tester.

2. Loose model test

The method comprises the following steps: rigid polyurethane foam has little difference in material properties, uniformity, usability, and the like, and thus is used as a substitute for bone materials. Grade 20 (0.32 g/cm) was selected according to the American society for testing and materials (ASTM: F1839-08) Specification ³ ) Standard rigid polyurethane foam was used as a standard test piece for bone model replacement.

Sample: the product of example 5.

Partial loosening model test: drilling a drill bit with the diameter of 1.0mm on a test piece (Shanghai supergroup rubber plastic limited company, china), screwing a self-tapping screw with the diameter of 1.5mm (Guangzhou Hua Chuan medical treatment, china), and axially pulling out the drill bit by a mechanical tester to measure the axial pulling-out force of a screw in a blank group; screwing out the screw after screwing in the screw, screwing in the screw again along the original nail channel, and measuring the second axial anti-pulling force; and simultaneously, screwing the film coated screw in again to detect the axial anti-pull-out force.

Complete loosening model test: drilling holes on a drill bit with the diameter of 1.5mm to cause a completely loosened nail channel, screwing in a self-tapping screw with the diameter of 1.5mm, screwing in a film-coated screw again, and detecting axial withdrawal force; all tests were repeated 5 times.

The results are shown in FIG. 10, where a is the plot of the pullout force of the screw in the in vitro standard test piece for the first axial pullout force, the second axial pullout force, and the complete loosening. And b, under the condition of partial looseness, screwing the condom screws of each group into the original nail channel after combining, and carrying out extraction force test to obtain an extraction force curve. And c, under the condition of complete loosening, screwing each group of condoms into the nail channel after combining the condoms with the bolts, and performing extraction force test to obtain an extraction force curve. d is the comparison of the magnitudes of the primary axial extraction force, the secondary axial extraction force and the extraction force under the condition of complete loosening in the standard test piece. And e is the axial extraction force after the condoms of each group are combined with the screws under the condition of partial looseness. f is the axial extraction force after the condom and the screw are combined under the condition of complete looseness. (n=5 for each group), < P < 0.05, (one-way ANOVA).

3. In vivo complete loosening model test

According to the results of the membrane mechanical test, the cell compatibility test and the in vitro anti-pulling test, the prepared membrane of the example 2 is selected for the in vivo complete loosening model test.

New Zealand white rabbits (males, average 2-2.5 kg). 10% of chloral hydrate, after anesthesia according to 3.5mL/kg intraperitoneal injection, preparing the skin of the bilateral hip joint, sterilizing and spreading, cutting the skin at the femoral trochanter for about 3cm, entering exposed bone tissues layer by layer, and preparing the intertrochanteric incomplete fracture by an electric saw, wherein the three groups are as follows: an electric drill with the diameter of 1.5mm is perpendicular to the fracture line, and is respectively screwed in by self-tapping screws with the diameter of 1.5mm (complete loosening group), and the coating material is screwed in by backward screws (condom group); the looseness-free group is screwed by self-tapping metal screws with the diameter of 1.5mm after drilling by a drill with the diameter of 1.0 mm. After closing the incision, 8 ten thousand units of penicillin are intramuscular injected into the double lower limbs for 3 days to prevent infection. The result is shown in fig. 11, wherein a is a schematic diagram of the operation; b is a schematic diagram of the arrow nail path and the fracture line position; c is a schematic diagram of the use of a conventional set of screws; d is a schematic diagram of the use of experimental group screws;

imaging examination: the first Day (Day 1) and fourth Day (Day 28) after the operation, and the result of CBCT examination at 4 weeks after the operation is shown in fig. 11, wherein e is a schematic diagram of a control fracture; f is a schematic diagram of the non-loosening group after healing; g is a schematic diagram of a CBCT examination result of the looseness group; h is a schematic diagram of a condom group (MS-CL) fracture; i is a schematic diagram of a condom group after healing; j is a CBCT examination result schematic diagram of the condom group; k is a schematic representation of a complete loosening group (NS-CL) fracture; l is a schematic diagram after healing of the complete loosening group; m is a schematic diagram of the complete loose group CBCT examination result.

The foregoing detailed description is directed to one of the possible embodiments of the present invention, which is not intended to limit the scope of the invention, but is to be accorded the full scope of all such equivalents and modifications so as not to depart from the scope of the invention.

Claims (4)

1. The preparation method of the hollow porous nano/micron fiber membrane is characterized by comprising the following steps of:

(1) Dispersing graphene oxide in dichloromethane or hexafluoroisopropanol to prepare a solution, and dissolving polyhydroxyalkanoate and polyethylene glycol in the solution to obtain a solution A;

(2) Dissolving polyethylene glycol in water to obtain solution B;

(3) Taking a syringe, respectively loading a solution A and a solution B, using a coaxial spray head, taking the solution A as a shell layer, taking the solution B as a core layer, using a high-speed orientation device as a receiver, setting positive voltage, negative voltage, temperature, pushing speed and receiving distance to prepare a fiber film, placing the fiber film in an aqueous solution, carrying out ultrasonic vibration to obtain a nano/micro fiber film with an ordered-disordered hollow porous structure, repeatedly soaking the fiber film in a solution with an osteogenic active peptide or a natural small molecular compound, and carrying out vacuum drying and sterilization;

in the step (3), the specification of the injector is 5mL; the positive voltage is 15kV, the negative voltage is 5kV, the temperature is 37 ℃, the injection speed is 0.5/0.1mm/min, and the receiving distance is 15-20cm; the dried product was then dried in a vacuum dryer for 48 hours, and the residual organic solvent was evaporated.

2. The method of preparing a hollow porous nano/micro fiber membrane according to claim 1, wherein in the step (3), the osteogenic active peptide or natural small molecule compound comprises: arg-Gly-Asp peptide, collagen mimetic peptide P-15, heparin binding peptide, bone morphogenetic protein-7 derived peptide, bone morphogenetic protein-2 derived peptide, glucagon-like peptide-1, osteogenic growth peptide, parathyroid hormone-related peptide, QK peptide, promin-1 derived peptide; any one or more of quercetin, puerarin, resveratrol, curcumin, epigallocatechin gallate and berberine.

3. A nano/micro fiber film prepared by the preparation method of the nano/micro fiber film according to any one of claims 1-2, wherein the nano/micro fiber film is in a film shape or a hollow or solid cylinder shape or a screw sleeve shape.

4. A functional absorbable orthopedic screw sleeve prepared from the fibrous membrane of claim 3, the preparation method of the orthopedic screw sleeve comprising the following steps:

according to the diameter and length requirements of the clinical orthopaedics screw, the intelligent rolling shaft is used for making the fibrous membrane with the same thickness into sleeve shapes with different diameters and different lengths, and the fibrous membrane is integrated with the screw body.

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