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CN-122005926-A - Biological ink and preparation method and application thereof

CN122005926ACN 122005926 ACN122005926 ACN 122005926ACN-122005926-A

Abstract

The invention provides biological ink and a preparation method and application thereof, and belongs to the technical field of medical equipment. The preparation method comprises the steps of (1) adding biological raw materials into phosphate buffer solution, stirring at constant temperature until the biological raw materials are completely dissolved to obtain solution of the biological raw materials, (2) dropwise adding methacrylic anhydride into the solution of the biological raw materials for reaction, adding the phosphate buffer solution, stirring to terminate the reaction, dialyzing and freeze-drying to obtain the methacryloylated biological material, (3) mixing the methacryloylated biological material, sodium alginate and water to obtain pregelatinized solution, and (4) adding a photoinitiator into the pregelatinized solution to obtain the biological ink. According to the invention, through optimizing printing materials and processes and selecting specific biological ink components to be combined with specific printing conditions, under the proper ultraviolet irradiation condition, specific reactions occur between raw materials of the biological ink, namely, after printing, the vascular stent, artificial blood vessel or vascular organ chip with proper mechanical properties, biocompatibility and the like is obtained.

Inventors

  • ZHANG WEI
  • SUN DI
  • WANG CHENGMING
  • Peng Minyong
  • WU ZHIYUAN
  • LI XIAORUI
  • Xing Chenxu

Assignees

  • 首都医学科学创新中心

Dates

Publication Date
20260512
Application Date
20250225

Claims (10)

  1. 1. The preparation method of the biological ink is characterized by comprising the following steps: (1) Adding biological raw materials into phosphate buffer solution, and stirring at constant temperature until the biological raw materials are completely dissolved to obtain a solution of the biological raw materials; (2) Dripping methacrylic anhydride into the solution of the biological raw materials, reacting, adding phosphate buffer solution, stirring to terminate the reaction, dialyzing, and freeze-drying to obtain a methacryloylated biological material; (3) Mixing the methacryloylated biomaterial, sodium alginate and water to obtain a pregel solution; (4) And adding the photoinitiator and the light blocker into the pregel solution to obtain the biological ink.
  2. 2. The method according to claim 1, wherein, In the step (1), the biological raw materials comprise gelatin, sodium alginate, chitosan, silk fibroin or polylysine; In the step (1), the concentration of the solution of the biological raw material is 1-10wt%.
  3. 3. The method according to claim 1, wherein, In the step (2), the reaction temperature is 40-60 ℃, the reaction time is 1-5 h, preferably, the reaction temperature is 50 ℃, and the reaction time is 3h; in the step (2), the volume ratio of methacrylic anhydride, the solution of biological raw materials and the phosphate buffer solution is 5:100:250; In step (2), the methacryloylated biomaterial comprises methacryloylated gelatin, methacryloylated sodium alginate, methacryloylated chitosan, methacryloylated silk fibroin, or methacryloylated polylysine.
  4. 4. The method according to claim 1, wherein, In the step (3), the concentration of the methacryloylated biomaterial in the pregel solution is 5-10 wt% and the concentration of sodium alginate is 5-10 wt%.
  5. 5. The method according to claim 1, wherein, In step (4), the photoinitiator comprises phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate, 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone, 2-hydroxy-2-methyl-1-phenyl-1-propanone; In the step (4), the mass concentration of the photoinitiator in the pregel solution is 0.01-0.1wt%; In the step (4), the light blocking agent is lemon yellow, and the mass concentration of the light blocking agent in the pregel solution is 0.01-0.1wt%.
  6. 6. Use of the bio-ink according to any one of claims 1-5 for printing vascular stents, vascular prostheses or vascular organ-chips in 3D printing.
  7. 7. The use according to claim 6, characterized in that it comprises the steps of: and pouring the biological ink into a printing position of a 3D DLP printer for printing, setting a printing model, and performing photo-crosslinking reaction under the action of ultraviolet light to print the biological ink to form a vascular stent, an artificial blood vessel and a vascular organ chip.
  8. 8. The use according to claim 7, wherein, In the printing process, the printing device is divided into a main body layer and a construction platform layer, wherein the construction platform layer adopts the intensity of 18 mw/cn 2 , the exposure time is 3s, three layers are selected, the height of each layer is 0.1mm, the intensity of the main body layer is 21mw/cn 2 , and the exposure time is 6s.
  9. 9. The use according to claim 7, wherein, When the biological ink is used for printing the vascular stent, the ultraviolet light source is arranged at the bottom of the tiled biological ink; when the biological ink is used for printing artificial blood vessels, the ultraviolet light source is positioned on two opposite sides of the tiled biological ink.
  10. 10. The use according to claim 7, wherein, When the biological ink is used for printing blood vessel organ chips, the ultraviolet light source is arranged at the bottom of the tiled biological ink.

Description

Biological ink and preparation method and application thereof Technical Field The invention belongs to the technical field of medical equipment, and particularly relates to biological ink and a preparation method and application thereof. Background With the rapid development of 3D printing, the application of 3D printing technology in the vascular industry has been significantly advanced, especially in the aspects of development of bio-ink, innovation of printing technology, and construction of vascular models. These advances provide new possibilities for vascular tissue repair and regenerative medicine. A vascular stent is a medical device for treating vascular diseases, and is generally made of metal or polymer materials, and is used for supporting stenosed or occluded blood vessels, reducing elastic retraction and reshaping of the blood vessels, and thus maintaining lumen blood flow. Vascular prostheses are medical devices used to replace or repair damaged or missing blood vessels, have a complex structure resembling human blood vessels, and are typically made of synthetic or biological materials. Such vascular prostheses also face the challenges of biocompatibility, antithrombotic and tissue regeneration. The vascular organ chip is a bionic micro-physiological system constructed based on a micro-fluidic technology and cell engineering, and is used for researching vascular biology, drug reaction, disease mechanism and the like by simulating the vascular structure and function of a human body. However, it still faces challenges in terms of bio-ink performance, etc. Hydrogel materials, which are the main components of bio-ink, have been gradually applied to research of the vascular industry in recent years due to their good biocompatibility and degradability. However, the hydrogel has poor biocompatibility and mechanical properties due to the influences of the composition, the reaction conditions and the like, so that the large-scale use of the hydrogel is still limited. Disclosure of Invention The invention provides a biological ink, a preparation method and application thereof, and a vascular stent, an artificial blood vessel, a vascular organ chip and the like printed by the biological ink under a certain condition have good biocompatibility and mechanical properties. The invention provides a preparation method of biological ink, which comprises the following steps: (1) Adding biological raw materials into phosphate buffer solution, and stirring at constant temperature until the biological raw materials are completely dissolved to obtain a solution of the biological raw materials; (2) Dripping methacrylic anhydride into the solution of the biological raw materials, reacting, adding phosphate buffer solution, stirring to terminate the reaction, dialyzing, and freeze-drying to obtain a methacryloylated biological material; (3) Mixing the methacryloylated biomaterial, sodium alginate and water to obtain a pregel solution; (4) And adding the photoinitiator and the light blocker into the pregel solution to obtain the biological ink. Further, in the step (1), the biological raw material comprises gelatin, sodium alginate, chitosan, silk fibroin or polylysine; In the step (1), the concentration of the solution of the biological raw material is 1-10wt%. Further, in the step (2), the reaction temperature is 40-60 ℃, the reaction time is 1-5 h, preferably, the reaction temperature is 50 ℃, and the reaction time is 3h; in the step (2), the volume ratio of methacrylic anhydride, the solution of biological raw materials and the phosphate buffer solution is 5:100:250; In step (2), the methacryloylated biomaterial comprises methacryloylated gelatin, methacryloylated sodium alginate, methacryloylated chitosan, methacryloylated silk fibroin, or methacryloylated polylysine. Further, in the step (3), the concentration of the methacryloylated biomaterial in the pregelatinized solution is 5-10 wt% and the concentration of sodium alginate is 5-10 wt%. Further, in step (4), the photoinitiator comprises phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate, 2-hydroxy-2-methyl-1- [4- (2-hydroxyethoxy) phenyl ] -1-propanone, 2-hydroxy-2-methyl-1-phenyl-1-propanone; In the step (4), the mass concentration of the photoinitiator in the pregel solution is 0.01-0.1wt%; In the step (4), the light blocking agent is lemon yellow, and the mass concentration of the light blocking agent in the pregel solution is 0.01-0.1wt%. The invention also provides application of any biological ink in 3D printing, wherein the biological ink is used for printing vascular stents, artificial blood vessels or vascular organ chips. Further, the application comprises the steps of: and pouring the biological ink into a printing position of a 3D DLP printer for printing, setting a printing model, and performing photo-crosslinking reaction under the action of ultraviolet light to print the biological ink to form a vascular stent, an artificial blood vessel and a