CN110063815A - A kind of direct write preparation method of the artificial blood vessel using ultrasonic nozzle preparation with spiral fold inwall - Google Patents

Abstract

The present invention relates to the ultrasonic nozzle preparation methods that a kind of application longitudinal wave prepares intravascular stent, belong to mechanical subject, biological manufacturing field.Using the method, preparation artificial blood vessel has become the big research hotspot of biological manufacturing field one.By reasonably applying ultrasonic spiral vibrating on direct write extrusion device, when so that hydrogel squeezing out, the artificial blood vessel's material contacted with vibration core is by along the Hybrid transducer vibration stress squeezed out on direction, the spiral flow of the minute yardstick of certain thickness is formed, and the surface topography for spiral fold of finally rerunning a movie out on crosslinking curing tubular fiber inner wall；It is allowed to be more nearly blood vessel physiological characteristic.

Description

A kind of direct writing of artificial blood vessel with spiral fold inner wall prepared by ultrasonic nozzle Preparation

technical field

The invention relates to a method for preparing an ultrasonic nozzle for preparing a vascular stent by applying longitudinal waves, and belongs to the field of mechanical science and biological manufacturing.

Background technique

The artificial blood vessels prepared by traditional methods (such as electrospinning technology, pouring technology infusion or traditional 3D printing technology) do not have the fold characteristics of real blood vessels on the inner wall surface, and are prone to thrombosis after transplantation. Compared with ordinary methods and equipment for preparing artificial blood vessels, small-diameter artificial blood vessels can be prepared by coaxial direct writing through ultrasonic spiral vibration nozzles, and the surface of artificial blood vessels can form spiral folds, making it closer to the physiological structure of the real blood vessel surface. The blood flows through the blood vessel to form a spiral flow to scour the inner wall of the blood vessel, thereby inhibiting the formation of thrombosis.

At present, with the rise of bio-3D printing, the use of sodium alginate, chitosan and other hydrogels that can be quickly reacted and cross-linked and cured are used as carrier materials for drugs and cells, and hollow fibers are directly formed by coaxial direct writing. Artificial blood vessels or biological scaffolds deposited with them as basic units have a certain geometric shape, and have good application prospects in the fields of tissue engineering, pharmacy and clinical medicine. The preparation of artificial blood vessels by this method has become a research hotspot in the field of biomanufacturing. By reasonably applying ultrasonic spiral vibration on the direct writing extrusion device, when the hydrogel is extruded, the artificial blood vessel material in contact with the vibrating core is subjected to longitudinal-torsional compound vibration stress along the extrusion direction, forming a certain layer thickness. Micro-scale helical flow, and finally reflected the surface morphology of helical folds on the inner wall of the cross-linked and solidified tubular fibers.

The international patent document (application number PCT/CN2014/078238) relates to a medical biological tissue structure and its preparation method and special equipment. Then, the biological material is sprayed and adhered to the hollow tube to form a functional layer, and then stacked layer by layer to form a composite body, and finally the synthetic polymer solution is sprayed on the outer surface of the composite body to form a three-dimensional structure. complex. On the basis of this patent, the Chinese patent document (application number CN201410589938.1) relates to a one-stop preparation method for vascularized life structures, which is positioned in the integrated manufacturing of life structures and realizes the realization of cells, structural materials, and growth factors. Simultaneous processing of other multi-scale objects, thereby greatly reducing the complexity of traditional biofabrication. The preparation system consists of a syringe pump, two medical piston syringes, and a coaxial nozzle. The biological material stock solution and the cross-linking agent stock solution are respectively introduced into the coaxial nozzle under the push of the syringe pump. The nozzle extrudes the cross-linked and solidified hollow fiber. This design method has the advantages of multi-objective, multi-scale and simple process. However, neither of the above two patents can extrude cross-linked and solidified hollow fibers with spiral folds. Different from the above two patent devices, the core of this design adopts an ultrasonic horn to connect with a stainless steel needle, and there is a spiral groove on the horn. Distribution, by installing the ultrasonic spiral vibration nozzle, the hydrogel has a longitudinal torsional composite vibration along the extrusion direction when extruding, so as to extrude the cross-linked and solidified hollow fibers with spiral wrinkles on the inner wall, so that the hydrogel is extruded along the extrusion direction. There is a longitudinal-torsional composite vibration in the outgoing direction to extrude the cross-linked and solidified hollow fibers with spiral folds on the inner wall.

SUMMARY OF THE INVENTION

In order to solve the disadvantage that the artificial blood vessel prepared by the existing equipment and method cannot form helical folds on the inner surface of the blood vessel, an ultrasonic spiral vibration nozzle is used, so that when the cross-linked and solidified hydrogel is extruded, there will be a longitudinal direction along the extrusion direction. Torsional composite vibration, the artificial blood vessel material in contact with it will reflect the surface morphology of the spiral folds under the action, making it closer to the physiological characteristics of blood vessels.

In order to achieve the above purpose, the present patent adopts the following scheme: a direct writing method for preparing an artificial blood vessel with a spiral folded inner wall using an ultrasonic nozzle, comprising an ultrasonic transducer (101), a hollow spiral groove ultrasonic horn ( 102), fixing bracket (103), inner needle or solid needle (104), outer needle (105), transducer housing (106), fixing bolt (107), flange plate (108), special tee (109) ), tower type anti-suck back rubber pad (110), heating rod (111) as shown in Figure 1. It is characterized in that: a transducer housing (106), an ultrasonic transducer (101), a horn and an inner needle or a solid needle (104), the outer needle (105) is coaxially installed, and the outer needle (105) and the inner needle Or the coaxiality of the thin solid needle bar (104) is ensured by the cooperation with the inner and outer cylindrical surfaces of the special tee (109), and the outer needle (105) and the special tee (109) adopt an interference fit. The lower end of the transducer housing (106) is connected to the flange (108) through fixing bolts (107), and the upper end of the special tee (109) is also connected to the flange (108) through fixing bolts (107). The solid needle (104) is helically connected to the lower end of the helical groove type ultrasonic horn (102), the surface of the hollow helical groove type ultrasonic horn (102) has evenly distributed helical grooves, and the heating rod (111) is embedded in the surface. In the special tee (109); the required special tee (109) is made of aluminum alloy, and its coaxiality with the horn is in contact with the circular surface of the flange (108) through the upper circular surface , ensure the tight connection with multiple bolts, and install a small cylindrical heating rod (111) in the wall thickness of the special tee (109) for heating during the extrusion process; the required heating rod (111), choose heating The size of the rod must be compatible with the wall thickness of the special tee (109), so the smaller size is used for easy installation; the selected heating rod is connected to the electronic display through heat-resistant wires, and must be used in conjunction with the thermocouple in the working process until it reaches the desired temperature.

A direct-writing preparation method for preparing artificial blood vessels with a spirally folded inner wall by using an ultrasonic nozzle, characterized in that: as shown in Figure 2, the preparation of hollow fibers is as follows, and the raw material liquid flows into the lumen through the three-way boss (201), cross-linking The agent is in contact with the raw material solution at the bottom through the inner needle cavity (202) or the solid needle, and is immediately cross-linked and solidified. Due to the vibration of the longitudinal-torsion compound, the cross-linked solidified tubular shape with the surface morphology of the spiral folds on the inner wall is finally reflected. Fiber (203).

A direct-writing preparation method for preparing an artificial blood vessel with a spirally folded inner wall using an ultrasonic nozzle, the specific preparation steps are as follows:

1. Preparation of stock solution: The biological material and its cross-linking agent are respectively prepared into a biological material stock solution and a cross-linking agent stock solution with a corresponding solvent according to a set ratio. 4% sodium alginate sol and 3% calcium chloride solution;

2. Equipment connection: connect the ultrasonic generator to the ultrasonic transducer, the stainless steel inner needle or solid needle is screwed with the horn, the outer needle is connected to the special tee, and the last tee is connected to the flange, all of the above is a coaxial installation;

3. Release of cross-linking agent and biological material stock solution: 4% sodium alginate sol flows in from the tee boss and flows down the inner needle, 3% calcium chloride solution flows out from the inner needle, and the outlet is mixed with the biological material stock solution. Cross-linking, in this process, the extrusion power is provided by the syringe pump, and at the same time, the mechanical wave is transmitted to the spiral groove ultrasonic horn through the conversion of the ultrasonic transducer, so as to give the stainless steel inner needle or solid needle a longitudinal torsion compound vibration ;

4. Preparation of hollow fibers: 4% sodium alginate sol and 3% calcium chloride solution are cross-linked in the outer needle to form a coaxial fluid, and the formed annular biomaterial stock solution is cross-linked and solidified by the cross-linking agent stock solution in the core, and the solution is released. After leaving the outer needle, a tubular hollow fiber with spiral folds is formed;

5. At the end of the test, turn off the syringe pump and disconnect the ultrasonic generator.

Compared with the prior art, the present invention has the following outstanding substantive features and remarkable technical progress

1. In this patent, the hollow spiral horn and the special tee can satisfy the extrusion of a single material or the cross-linked extrusion of two materials;

2. The existing artificial blood vessels are mostly in the form of no surface helical folds. This patent uses a helical groove ultrasonic vibrator, the longitudinal component and the torsional component are increased, and the prepared artificial blood vessels with helical folds are closer to the physiological environment. vascular structure;

3. In this patent, a heating rod is embedded in a special tee, which can be heated to keep it in a molten state during the extrusion of a single material;

4. In this patent, the transducer shell plays a protective role, and a plurality of holes are opened in its structure to dissipate heat during its operation;

5. The tower-type anti-suckback rubber pad can block the influx of experimental materials into the upper half of the tee to prevent the impact on the horn.

Description of drawings

Fig. 1 is a structural schematic diagram;

Figure 2 is a schematic diagram of a hollow fiber with a spiral shape on the extruded surface

Figure 3 is a top view of the structure

In Fig. 1, ultrasonic vibration transducer (101), helical groove ultrasonic horn (102), fixing bracket (103), inner needle or thin solid needle bar (104), outer needle (105), transducer housing (106), fixing bolts (107), flanges (108), special tee (109), anti-sucking sponge (110), heating rod (111);

In Fig. 2, the tee boss (201), the inner needle lumen (202), and the cross-linked and solidified tubular fibers (203) with the surface morphology of the spiral folds.

specific embodiment

Example 1: Preparation of sodium alginate-calcium chloride hollow fibers with spiral texture

1. Screw the inner needle or solid needle (104) around the thread to the lower end of the helical groove ultrasonic horn (102);

2. Connect the transducer housing (106) protecting the ultrasonic transducer (101) to the flange (108) through fixing bolts (107);

3. The upper end of the special tee (109) is fixed on the flange (108), and the bracket of the fixing device is also fixed on the flange;

4. Connect the syringe filled with calcium chloride solution to the hollow part of the upper part of the transducer, connect the syringe filled with sodium alginate to the tee boss (201) with the corresponding leather tube, and fix the device through the fixing bracket (103). The whole is installed on the 3D bioprinter;

5. The two poles of the ultrasonic transducer (101) are connected to the ultrasonic generator, and at the same time, the sodium alginate-calcium chloride hollow fibers with spiral texture are obtained by extrusion.

Example 2: Direct extrusion of PLA material with spiral texture on the surface

1. Screw the inner needle or thin solid needle bar (104) around the thread to the lower end of the helical groove ultrasonic horn (102);

2. Connect the transducer housing (106) protecting the ultrasonic transducer (101) to the flange (108) through fixing bolts (107);

3. The upper end of the special tee (109) is fixed on the flange (108), and the fixing bracket (103) is also fixed on the flange (108);

4. Connect the molten PLA to the tee boss (201) through a pipe, and install it on the 3D bioprinter as a whole;

5. The heating rod (111) is heated first, until the temperature reaches the melting temperature of PLA;

6. The two poles of the ultrasonic transducer (101) are connected to the ultrasonic generator, and the PLA material with the spiral texture on the surface is extruded and cooled naturally.

Claims (5)

1. a kind of direct write preparation method of the artificial blood vessel with spiral fold inwall and ultrasonic Coaxial nozzle, including ultrasonic transduction Device (101), hollow screw groove type ultrasonic amplitude transformer (102), fixed bracket (103), interior syringe needle or solid syringe needle (104), Outer syringe needle (105), transducer enclosure (106), fixing bolt (107), ring flange (108), special threeway (109), tower is anti-down It inhales rubber pad (110), heating rod (111) such as Fig. 1 is it is characterized by: transducer enclosure (106), ultrasonic transducer (101), luffing Bar and interior syringe needle or solid syringe needle (104), outer syringe needle (105) are co-axially mounted, outer syringe needle (105) and interior syringe needle or thin solid needle bar (104) concentricity with the cooperation on the inside and outside cylindrical surface of special threeway (109) by respectively ensureing, outer syringe needle (105) and special Threeway (109) processed is using interference fit；Transducer enclosure (106) lower end is connected to ring flange by fixing bolt (107) (108), the upper end of special threeway (109) is connected to ring flange (108), interior syringe needle or solid needle also by fixing bolt (107) Head (104) is connect with screw groove type ultrasonic amplitude transformer (102) lower end spiral, hollow screw groove type ultrasonic amplitude transformer (102) there are equally distributed spiral grooves on surface, and heating rod (111) is inner embedded in special threeway (109).

2. the direct write preparation method of artificial blood vessel with spiral fold inwall according to claim 1 a kind of and ultrasound Coaxial nozzle, steps are as follows for specific preparation manipulation:

Syringe equipped with crosslinking agent passes through transducer enclosure and is connected with hollow portion at the top of energy converter；Note equipped with material stoste Emitter is connect with threeway boss, and syringe connects syringe pump；

Ultrasonic transducer is connected, mechanical wave is passed into screw groove type ultrasonic amplitude transformer, to give interior syringe needle or solid needle The vibration of first Hybrid transducer；

Extruded material, should be noted at this time must crosslinked fluid first squeeze out, conducive to hollow structure is formed；

It by fixed bracket, is integrally assemblied on 3D biometric print machine, there is the hollow of spiral fold by outer syringe needle expression surface Fiber；

Syringe pump is closed in off-test.

3. the direct write preparation method of artificial blood vessel with spiral fold inwall according to claim 1 a kind of and ultrasound Coaxial nozzle, required special threeway (109) are characterized in that material selection aluminium alloy, the concentricity with amplitude transformer passes through Upper circular face contacts with each other with ring flange (108) rounded face, closely connects guarantee with multiple bolts, in special threeway (109) The heating rod (111) of small cylindrical is packed into wall thickness, for the heating in extrusion process.

4. the direct write preparation method of artificial blood vessel with spiral fold inwall according to claim 1 a kind of and ultrasound Coaxial nozzle, required heating rod (111) are characterized in that, heating rod is selected to be adapted with special threeway (109) wall thickness greatly, so Small volume type is selected, is easily installed；Selected heating rod is connect by heat-resisting wire with electronic console, and in the course of work It must be used cooperatively with thermocouple, until reaching required temperature.

5. the direct write preparation method of artificial blood vessel with spiral fold inwall according to claim 1 a kind of and ultrasound Coaxial nozzle, prepares that doughnut operation is as follows, and by material stoste by threeway boss (201) inflow inner cavity, crosslinking agent passes through Interior needle lumen (202) or solid syringe needle are contacted in bottom with material stoste, and crosslinking curing immediately, since there are Hybrid transducers Vibration, have the crosslinking curing tubular fiber (203) of spiral wrinkled surface pattern on inner wall of finally rerunning a movie out.