Spray printing combined tool for in-situ preparation of vascular surgery and use method of spray printing combined tool

Abstract

The invention relates to the technical field of vascular repair surgeries, in particular to a jet printing combined tool for in-situ preparation of vascular surgeries and a use method of the jet printing combined tool. The jet printing combined tool comprises a sacrificial tubular stent and an annular printing nozzle, and the two ends of the sacrificial tubular stent are used for being inserted into two fractures of a vascular defect part respectively; the sacrificial tubular stent is dissolved in blood after blood circulation, and when the sacrificial tubular stent penetrates through the annular printing spray head, the moving annular printing spray head is used for spraying printing ink towards the peripheral wall of the sacrificial tubular stent; the interior of the annular printing nozzle is of a hollow tubular structure, a feeding port is formed in the outer side of the annular printing nozzle, and a plurality of discharging ports are formed in the inner side of the annular printing nozzle in the radial direction. The annular printing nozzle and the sacrificial tubular stent are simple and portable in equipment, simple in operation process, short in printing time consumption, capable of effectively shortening the operation duration, low in technical requirement, capable of promoting tissue reperfusion, reducing the amputation rate and improving prognosis and suitable for the environment with poor medical conditions.

Description

Technical Field

[0001] The present application relates to the technical field of vascular repair surgery, and in particular to a printing assembly tool for in-situ vascular preparation surgery and a method of using the same. Background Art

[0002] Blood vessels are important channels for transporting nutrients. If there are no blood vessels, it will affect the necrosis of the blood supply area, such as myocardial necrosis caused by coronary artery obstruction; limb amputation will lead to limb necrosis if only tissue suture is performed without treating blood vessels. At present, the main methods for vascular defects are autologous blood vessel transplantation and artificial blood vessel transplantation, but these two methods have their own disadvantages. Autologous blood vessel transplantation will cause damage to the donor area. For the elderly and patients with severe trauma, there are also problems such as poor quality of blood vessels in the donor area and few donor area options. Artificial small blood vessel transplants smaller than 6mm have poor patency. If severe trauma cannot be performed for vascular transplantation / anastomosis fine surgery, amputation will be considered to save life.

[0003] 3D bioprinting uses computer-aided accumulation to create objects with structures and sizes that match the target tissue, and can produce functional tissues or organs. Common 3D bioprinting technology requires first reconstructing a three-dimensional image of the defect through software, sending it to the printer, and then working. After printing is completed, it needs to be disinfected before moving to the defect site.

[0004] With respect to the above-mentioned related technologies, the inventor believes that there are the following technical defects that need to be improved:

[0005] The process of common 3D printing technology is cumbersome. Not only is the machine expensive and the production cost high, but the process is also complicated and time-consuming. There is also a risk of contamination during the transplantation process, and it is impossible to achieve the purpose of in situ printing of blood vessels. Summary of the invention

[0006] The present application provides a printing assembly tool for in-situ preparation of vascular surgery and a method of using the same to improve the following technical problems:

[0007] The process of common 3D printing technology is cumbersome. Not only is the machine expensive and the production cost high, but the process is also complicated and time-consuming. There is also a risk of contamination during the transplantation process, and it is impossible to achieve the purpose of in situ printing of blood vessels.

[0008] In a first aspect, the present application provides a printing assembly tool for in-situ preparation of vascular surgery, which adopts the following technical solution:

[0009] A printing combination tool for in-situ preparation of vascular surgery and a method of using the same, comprising a sacrificial tubular stent and an annular printing nozzle, wherein the two ends of the sacrificial tubular stent are respectively used to be inserted into two breaks of a vascular defect, the sacrificial tubular stent dissolves in the blood after blood circulation, and the moving annular printing nozzle is used to print ink toward the outer peripheral wall of the sacrificial tubular stent when the sacrificial tubular stent passes through the annular printing nozzle; the annular printing nozzle has an internal hollow tubular structure, a feed port is arranged on the outer side of the annular printing nozzle, and a plurality of discharge ports are radially arranged on the inner side of the annular printing nozzle.

[0010] In an achievable technical solution of the present application, the annular printing nozzle includes a first semi-annular tube, a second semi-annular tube, a plurality of liquid spraying tubes and a liquid inlet tube whose inner cavities are connected to each other, the liquid inlet tube is vertically connected to the outer side of the first semi-annular tube, the plurality of liquid spraying tubes are radially connected to the inner side of the first semi-annular tube, the plurality of liquid spraying tubes are radially connected to the inner side of the second semi-annular tube, the end of the first semi-annular tube and the end of the second semi-annular tube are detachably plug-assembled, the feed port is the outer end of the liquid inlet tube, and the discharge port is the inner end of the liquid spraying tube.

[0011] In an achievable technical solution of the present application, the length of the spray tube is 0.8-0.95 times the inner radius of the annular printing nozzle, and the number of the spray tubes is between 4-8, and the multiple spray tubes are evenly and symmetrically arranged along the annular printing nozzle, and the inner ends of the multiple spray tubes form a regular polygon structure for the sacrificial tubular bracket to pass through.

[0012] In an achievable technical solution of the present application, the outer diameter of the sacrificial tubular stent gradually decreases from one end toward the other end.

[0013] In an achievable technical solution of the present application, the manufacturing method of the annular printing nozzle is as follows: using three-dimensional drawing software to design the annular printing nozzle, and then using a 3D printer to print it to obtain a detachable annular printing nozzle;

[0014] The method for making the sacrificial tubular support is as follows: using three-dimensional drawing software to design the sacrificial tubular support, and then using a 3D printer to print it to obtain the sacrificial tubular support.

[0015] In an achievable technical solution of the present application, the printing raw material of the annular printing nozzle is red wax, and the printing raw material of the sacrificial tubular support is polyvinyl alcohol.

[0016] In an achievable technical solution of the present application, the three-dimensional drawing software is UG software, Pro / E software or SolidWorks software, the 3D printer used to make the annular printing nozzle is a DLP printer, and the 3D printer used to make the sacrificial tubular bracket is a fused deposition printer.

[0017] In a second aspect, the present application provides a method for using the above-mentioned printing assembly tool for in-situ preparation of blood vessels for surgery, which adopts the following technical solution:

[0018] A method for using a printing assembly tool for in-situ preparation of blood vessels for surgery comprises the following steps:

[0019] Step 1, preparing printing ink: dissolving o-nitrobenzyl alcohol-modified polyethylene glycol, methacrylate hyaluronic acid, and phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt in a phosphate buffer solution to obtain a hydrogel precursor solution, and mixing the hydrogel precursor solution with vascular endothelial cells as printing ink;

[0020] Step 2, assembling the printing: assembling the annular printing nozzle until the sacrificial tubular support passes through the annular printing nozzle, adding printing ink to the feed port of the annular printing nozzle through a syringe, gradually moving the annular printing nozzle along the sacrificial tubular support and evenly coating the printing ink on the outer peripheral wall of the sacrificial tubular support;

[0021] Step 3: Curing: Use ultraviolet light to perform light curing until the printed ink is cured into a tube shape.

[0022] In an achievable technical solution of the present application, in step 1, the mass concentration of o-nitrobenzyl alcohol-modified polyethylene glycol is 5-15%, the mass concentration of methacrylate hyaluronic acid is 1-3%, and the mass concentration of phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt is 0.4-0.6%.

[0023] In a feasible technical solution of the present application, the wavelength of the ultraviolet rays in step three is between 360-400nm.

[0024] In summary, the present application includes at least one of the following beneficial technical effects:

[0025] Based on the overlapping effect of the sacrificial tubular stent, the printing ink can be sprayed directly on the defective part of the blood vessel. As the printing ink solidifies and the sacrificial tubular stent dissolves, an "in situ vascular structure" is formed. The endothelial cells of the blood vessels in the defective part can grow into the inner wall of the printed "in situ vascular structure", replacing the existing in vitro 3D printing and then transferring to the incubator for incubation, reducing costs. In addition, the human body, as a natural bioreactor, is far superior to in vitro culture conditions in terms of tissue regeneration, and reduces the chance of contact contamination, making it safer.

[0026] With the assistance of sacrificial tubular stents, the degree of fit between the in-situ printed "in-situ vascular structure" and the size of the broken end of the vascular defect can be precisely controlled. The adhesion between the reconstructed blood vessel and the broken end of the blood vessel is enhanced through in-situ cross-linking, so that the tissue cells around the vascular defect grow into the "in-situ vascular structure" in a natural way, and the survival rate of the printed blood vessels is higher, thereby improving the quality of defective blood vessel repair.

[0027] A photo-cross-linked hydrogel with good biocompatibility is used. This hydrogel has the mechanical strength required for vascular tissue and is mixed with vascular endothelial cells as the raw material for extrusion printing. The printing ink is evenly applied to the sacrificial tubular stent using a circular nozzle. After the blood circulates again and the stent dissolves, a blood vessel that meets the size of the affected area can be obtained. The circular printing nozzle and the sacrificial tubular stent are simple and portable, with a simple operation process and a short printing time, which effectively shortens the operation time. The technical requirements are low, and the system can promote tissue reperfusion, reduce the amputation rate, and improve the prognosis. The system is suitable for environments with poor medical conditions and can meet the needs of immediate and rapid treatment on the spot in accidental disasters, battlefields, etc. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0029] Figure 1 It is a schematic diagram of the operating principle of the printing combination tool in the application embodiment.

[0030] Figure 2 It is a schematic diagram of the cross-sectional structure of the annular printing nozzle in the embodiment of the present application.

[0031] Figure 3 It is a modeling diagram of the sacrificial tubular support in the embodiment of the present application.

[0032] Figure 4 It is a physical picture of the sacrificial tubular support in the embodiment of the present application.

[0033] Figure 5 It is an operational experimental status diagram of the inkjet printing assembly tool in the application embodiment.

[0034] Figure 6 It is a flowchart of the method of using the printing combination tool of an embodiment of the present application.

[0035] Figure 7 It is a schematic diagram of the state of in situ vascular structure formation in the application embodiment.

[0036] Figure 8 It is a cross-sectional view of the in-situ blood vessel structure after printing in the application embodiment.

[0037] Description of reference numerals:

[0038] 100. Ring-shaped printing nozzle; 1. First semi-ring tube; 2. Second semi-ring tube; 3. Liquid spraying tube; 4. Liquid inlet tube; 200. Sacrificial tubular support. DETAILED DESCRIPTION

[0039] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the present application is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0040] It should be noted that when an element is referred to as being "fixed to" or "disposed on" another element, it can be directly on the other element or indirectly on the other element. When an element is referred to as being "connected to" another element, it can be directly connected to the other element or indirectly connected to the other element.

[0041] It should be understood that the terms "length", "width", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", etc., indicating the orientation or position relationship, are based on the orientation or position relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as a limitation on the present application.

[0042] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of this application, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0043] The following is combined with Figure 1-8 This application is described in further detail.

[0044] The present application embodiment discloses a printing assembly tool for in-situ preparation of blood vessels for surgery. Figure 1-8The printing assembly tool for in-situ preparation of vascular surgery includes a sacrificial tubular stent 200 and an annular printing nozzle 100. The two ends of the sacrificial tubular stent 200 are respectively used to be inserted into the two breaks of the vascular defect. The sacrificial tubular stent 200 dissolves in the blood after blood circulation. When the sacrificial tubular stent 200 passes through the annular printing nozzle 100, the moving annular printing nozzle 100 is used to print ink toward the outer peripheral wall of the sacrificial tubular stent 200; the internal hollow tubular structure of the annular printing nozzle 100, the outer side of the annular printing nozzle 100 is provided with a feed port, and the inner side of the annular printing nozzle 100 is radially provided with multiple discharge ports.

[0045] In an achievable technical solution of the present application, the annular printing nozzle 100 includes a first semi-annular tube 1, a second semi-annular tube 2, a plurality of liquid spraying tubes 3 and a liquid inlet tube 4 whose inner cavities are connected to each other, the liquid inlet tube 4 is vertically connected to the outer side of the first semi-annular tube 1, the plurality of liquid spraying tubes 3 are radially connected to the inner side of the first semi-annular tube 1, and the plurality of liquid spraying tubes 3 are radially connected to the inner side of the second semi-annular tube 2, the end of the first semi-annular tube 1 and the end of the second semi-annular tube 2 are detachably plug-assembled, the feed inlet is the outer end of the liquid inlet tube 4, and the discharge outlet is the inner end of the liquid spraying tube 3.

[0046] In an achievable technical solution of the present application, the length of the spray tube 3 is 0.8-0.95 times the inner radius of the annular printing nozzle 100 (try to ensure that each discharge port is close to the outer surface of the sacrificial tubular support 200200 to facilitate precise and uniform coating), and the number of the spray tubes 3 is between 4 and 8 (preferably 5), and the multiple spray tubes 3 are evenly and symmetrically arranged along the annular printing nozzle 100, and the inner ends of the multiple spray tubes 3 form a regular polygonal structure for the sacrificial tubular support 200 to pass through.

[0047] The annular printing nozzle 100100 designed as above has a simple structure and is easy to manufacture. It is very convenient to assemble and disassemble. In addition, it has multiple outlets, so the printing ink can be ejected from multiple outlets at the same time, which is convenient for rapid molding of in-situ vascular structures.

[0048] The outer diameter of the sacrificial tubular stent 200 gradually decreases from one end to the other end.

[0049] The method for making the annular printing nozzle 100 is as follows: using 3D drawing software to design the annular printing nozzle 100, and then using a 3D printer to print it to obtain a detachable annular printing nozzle 100;

[0050] The method for making the sacrificial tubular support 200 is as follows: the sacrificial tubular support 200 is designed using three-dimensional drawing software, and then printed using a 3D printer to obtain the sacrificial tubular support 200.

[0051] Specifically, the printing raw material of the annular printing nozzle 100 is red wax, the printing raw material of the sacrificial tubular support 200 is polyvinyl alcohol, the three-dimensional drawing software is UG software, Pro / E software or SolidWorks software, the 3D printer used to make the annular printing nozzle 100 is a DLP printer, and the 3D printer used to make the sacrificial tubular support 200 is a fused deposition printer.

[0052] The present application provides a method for using the above-mentioned inkjet printing assembly tool for in-situ preparation of blood vessels for surgery, which adopts the following technical solution:

[0053] A method for using a printing assembly tool for in-situ preparation of blood vessels for surgery comprises the following steps:

[0054] Step 1 S1, preparing printing ink: dissolving o-nitrobenzyl alcohol-modified polyethylene glycol, methacrylate hyaluronic acid, and phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt in a phosphate buffer solution to obtain a hydrogel precursor solution, and mixing the hydrogel precursor solution with vascular endothelial cells as printing ink;

[0055] Step 2 S2, assembling and printing: using a vascular clamp to stop bleeding at the defective part of the blood vessel, inserting the two ends of the sacrificial tubular stent 200 into the two broken ends of the defective part of the blood vessel respectively, assembling the annular printing nozzle 100 along the defective part of the blood vessel until the sacrificial tubular stent 200 passes through the annular printing nozzle 100, adding printing ink to the feed port of the annular printing nozzle 100 through a syringe, gradually moving the annular printing nozzle 100 along the sacrificial tubular stent 200 and evenly coating the printing ink on the outer peripheral wall of the sacrificial tubular stent 200;

[0056] Step three S3, curing treatment: use ultraviolet light from a UV lamp to perform light curing treatment until the printing ink is cured and formed into a tube, then disassemble and remove the annular printing nozzle 100, loosen the blood vessel clamp and allow blood to flow to dissolve the sacrificial tubular stent 200.

[0057] In step 1, the mass concentration of o-nitrobenzyl alcohol-modified polyethylene glycol is 5-15%, the mass concentration of methacrylate hyaluronic acid is 1-3%, and the mass concentration of phenyl (2,4,6-trimethylbenzoyl) lithium phosphate is 0.4-0.6%.

[0058] The wavelength of the ultraviolet light in step 3 is between 360-400 nm (preferably 365 nm).

[0059] In step 3 of this embodiment, the annular printing nozzle 100 is fixed by a mechanical arm to control the printing path, and the syringe is an electric syringe. In other embodiments, if there is no condition of a mechanical arm and an electric syringe, the annular printing nozzle 100 can also be fixed by a doctor holding it and controlling the printing path, and the syringe is a hand-push syringe.

[0060] The beneficial technical effects of the inkjet printing assembly tool for in-situ preparation of vascular surgery and the method of using the same in the embodiments of the present application are as follows:

[0061] Based on the overlapping effect of the sacrificial tubular stent 200, the printing ink can be directly sprayed on the defective part of the blood vessel. As the printing ink solidifies and the sacrificial tubular stent 200 dissolves, an "in situ vascular structure" is formed. The vascular endothelial cells at the defective part can grow into the inner wall of the printed "in situ vascular structure", replacing the existing in vitro 3D printing and then transferring to the incubator for incubation process, reducing costs. In addition, the human body, as a natural bioreactor, is far superior to in vitro culture conditions in terms of tissue regeneration, and reduces the chance of contact contamination, which is safer.

[0062] With the assistance of the sacrificial tubular stent 200, the degree of fit between the in-situ printed "in-situ vascular structure" and the size of the fracture of the defective part of the blood vessel can be accurately controlled, and the adhesion between the reconstructed blood vessel and the broken end of the blood vessel is enhanced through in-situ cross-linking, so that the tissue cells around the defective part of the blood vessel grow into the "in-situ vascular structure" in a natural way, and the survival rate of the printed blood vessel is higher, thereby improving the quality of defective blood vessel repair;

[0063] A photo-cross-linked hydrogel with good biocompatibility is used. This hydrogel has the mechanical strength required for vascular tissue and is mixed with vascular endothelial cells as the raw material for extrusion printing. The printing ink is evenly applied to the sacrificial tubular stent 200 using an annular nozzle. After the blood circulates again and the stent dissolves, a blood vessel that meets the size of the affected area can be obtained. The annular printing nozzle 100 and the sacrificial tubular stent 200 are simple and portable, with a simple operation process and a short printing time, which effectively shortens the operation time. The technical requirements are low, and the reperfusion of tissues is promoted, the amputation rate is reduced, and the prognosis is improved. The annular printing nozzle 100 and the sacrificial tubular stent 200 are suitable for environments with poor medical conditions and can meet the needs of immediate and rapid treatment on the spot in accidental disasters, battlefields, etc.

[0064] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the application should be included in the protection scope of the present application.

Claims

1. A printing assembly tool for in-situ preparation of blood vessels for surgery, characterized in that: The invention comprises a sacrificial tubular stent (200) and an annular printing nozzle (100), wherein the two ends of the sacrificial tubular stent (200) are respectively used to be inserted into two fractures of a vascular defect, the sacrificial tubular stent (200) dissolves in the blood after blood circulation, and when the sacrificial tubular stent (200) passes through the annular printing nozzle (100), the moving annular printing nozzle (100) is used to spray printing ink toward the outer peripheral wall of the sacrificial tubular stent (200); the inner hollow tubular structure of the annular printing nozzle (100) is provided with a feed port on the outer side of the annular printing nozzle (100), and a plurality of discharge ports are radially provided on the inner side of the annular printing nozzle (100).

2. The inkjet printing assembly tool for in-situ preparation of blood vessels for surgery according to claim 1, characterized in that: The annular printing nozzle (100) comprises a first semi-annular tube (1), a second semi-annular tube (2), a plurality of liquid spraying tubes (3) and a liquid inlet tube (4) whose inner cavities are interconnected, the liquid inlet tube (4) being vertically connected to the outer side of the first semi-annular tube (1), the plurality of liquid spraying tubes (3) being radially connected to the inner side of the first semi-annular tube (1), the plurality of liquid spraying tubes (3) being radially connected to the inner side of the second semi-annular tube (2), the end of the first semi-annular tube (1) and the end of the second semi-annular tube (2) being detachably plug-connected and assembled, the feed inlet being the outer end of the liquid inlet tube (4), and the discharge outlet being the inner end of the liquid spraying tube (3).

3. The inkjet printing assembly tool for in-situ preparation of blood vessels for surgery according to claim 2, characterized in that: The length of the liquid spray pipe (3) is 0.8-0.95 times the inner radius of the annular printing nozzle (100), and the number of the liquid spray pipes (3) is between 4 and 8, and the plurality of liquid spray pipes (3) are evenly and symmetrically arranged along the annular printing nozzle (100), and the inner ends of the plurality of liquid spray pipes (3) form a regular polygonal structure for the sacrificial tubular support (200) to pass through.

4. The inkjet printing assembly tool for in-situ preparation of blood vessels for surgery according to claim 1, characterized in that: The outer diameter of the sacrificial tubular stent (200) gradually decreases from one end to the other end.

5. The inkjet printing assembly tool for in-situ preparation of blood vessels for surgery according to claim 2, characterized in that: The manufacturing method of the annular printing nozzle (100) is as follows: using three-dimensional drawing software to design the annular printing nozzle (100), and then using a 3D printer to print it to obtain a detachable annular printing nozzle (100); The method for manufacturing the sacrificial tubular support (200) is as follows: using three-dimensional drawing software to design the sacrificial tubular support (200), and then using a 3D printer to print it to obtain the sacrificial tubular support (200).

6. The inkjet printing assembly tool for in-situ preparation of blood vessels for surgery according to claim 5, characterized in that: The printing material of the annular printing nozzle (100) is red wax, and the printing material of the sacrificial tubular support (200) is polyvinyl alcohol.

7. The inkjet printing assembly tool for in-situ preparation of blood vessels for surgery according to claim 5, characterized in that: The three-dimensional drawing software is UG software, Pro / E software or SolidWorks software, the 3D printer used to manufacture the annular printing nozzle (100) is a DLP printer, and the 3D printer used to manufacture the sacrificial tubular support (200) is a fused deposition type printer.

8. A method for using the inkjet printing assembly tool for in-situ vascular preparation surgery as claimed in any one of claims 1 to 7, characterized in that: The steps include: Step 1, preparing printing ink: dissolving o-nitrobenzyl alcohol-modified polyethylene glycol, methacrylate hyaluronic acid, and phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt in a phosphate buffer solution to obtain a hydrogel precursor solution, and mixing the hydrogel precursor solution with vascular endothelial cells as printing ink; Step 2, assembling and printing: assembling the annular printing nozzle (100) until the sacrificial tubular support (200) passes through the annular printing nozzle (100), adding printing ink to the feed port of the annular printing nozzle (100) through a syringe, gradually moving the annular printing nozzle (100) along the sacrificial tubular support (200) and evenly coating the printing ink on the outer peripheral wall of the sacrificial tubular support (200); Step 3: Curing: Use ultraviolet light to perform light curing until the printed ink is cured into a tube shape.

9. The method for using the inkjet printing assembly tool for in-situ preparation of blood vessels according to claim 8, characterized in that: In step 1, the mass concentration of o-nitrobenzyl alcohol-modified polyethylene glycol is 5-15%, the mass concentration of methacrylate hyaluronic acid is 1-3%, and the mass concentration of phenyl (2,4,6-trimethylbenzoyl) phosphate lithium salt is 0.4-0.6%.

10. The method for using the inkjet printing assembly tool for in-situ vascular preparation surgery according to claim 8, characterized in that: The wavelength of the ultraviolet light in step three is between 360-400nm.

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