CN114058011A - Preparation method and application of epsilon-polylysine derivative biological ink - Google Patents
Preparation method and application of epsilon-polylysine derivative biological ink Download PDFInfo
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- CN114058011A CN114058011A CN202210025227.6A CN202210025227A CN114058011A CN 114058011 A CN114058011 A CN 114058011A CN 202210025227 A CN202210025227 A CN 202210025227A CN 114058011 A CN114058011 A CN 114058011A
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- polylysine
- biological ink
- ink
- aqueous solution
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- 108010039918 Polylysine Proteins 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000007864 aqueous solution Substances 0.000 claims abstract description 14
- 239000008367 deionised water Substances 0.000 claims abstract description 13
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 13
- 238000010146 3D printing Methods 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 238000009777 vacuum freeze-drying Methods 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 4
- 238000000016 photochemical curing Methods 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims abstract 3
- 239000000243 solution Substances 0.000 claims description 21
- 239000003999 initiator Substances 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 125000003700 epoxy group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 238000007259 addition reaction Methods 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 238000007142 ring opening reaction Methods 0.000 claims 1
- 239000008204 material by function Substances 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 7
- 238000007639 printing Methods 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000000502 dialysis Methods 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 3
- 229920006317 cationic polymer Polymers 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- -1 hydrogen ions Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- 125000005395 methacrylic acid group Chemical group 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000004298 light response Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Images
Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/48—Polymers modified by chemical after-treatment
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Materials Engineering (AREA)
- General Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Epoxy Resins (AREA)
Abstract
The invention belongs to the technical field of new functional materials, and the specific technical scheme is as follows: the epsilon-polylysine derivative biological ink is prepared by carrying out chemical reaction on glycidyl methacrylate and epsilon-polylysine, and can be converted from a liquid state into a gel state under the irradiation of an ultraviolet light source under the action of a photoinitiator; the preparation method comprises the following steps: mixing the epsilon-polylysine aqueous solution and the glycidyl methacrylate according to the volume ratio of 50:1-5, reacting for 4-8h at the temperature of 50-80 ℃, dialyzing and removing unreacted substances, carrying out vacuum freeze drying, and dissolving with deionized water to obtain the biological ink; the specific application is as follows: the biological ink is characterized by having photoresponse capability, being capable of being converted from a liquid state into a gel state under the irradiation of ultraviolet light, thereby completing photocuring 3D printing, and being efficient, stable and safe.
Description
Technical Field
The invention belongs to the technical field of new functional materials, and particularly relates to a preparation method and application of epsilon-polylysine biological ink with a light response characteristic.
Background
3D printing (also known as "additive manufacturing") has become an important force to drive a new round of technological innovation and industrial revolution. The biomedical field is an important application field of the 3D printing technology due to the characteristics of large demand, high individuation degree and high product added value. Although biological 3D printing technology has been applied to the fields of preoperative planning, external medical auxiliary instruments and the like, and the development is in the future towards degradable internal implants and 3D printing of biological tissues/organs and the like, the selection of suitable ink materials is still a big problem faced by biological 3D printing, and medical 3D printing materials become the bottleneck of industrial development.
Epsilon-polylysine is a natural polymer material, is usually prepared by microbial fermentation, has a molecular weight of between 3000 and 5000 Da, and has a large amount of amino active groups on a molecular chain. The cationic polymer can be combined with hydrogen ions to carry positive charges to form a cationic polymer in an aqueous solution or an acidic environment, the cationic polymer can be well combined on the surface of a cell to achieve the purpose of adhering the cell, the biocompatibility is good, and the degradation product lysine is amino acid necessary for a human body. Currently, in the field of biomaterial medicine, since epsilon-polylysine is rich in cations, can generate strong electrostatic force with substances having anions, and has good penetration to biological membranes, it is currently used as a carrier for some drugs.
Disclosure of Invention
In order to solve the technical problems in the prior art, the invention provides the epsilon-polylysine biological ink with the photoresponse characteristic, the biological ink is obtained by reacting the epsilon-polylysine with glycidyl methacrylate, the glycidyl methacrylate is a monomer simultaneously having acrylate groups and epoxy groups, the reactivity of the acrylate groups is higher, the acrylic ink can carry out self-polymerization reaction, and the acrylic ink can also carry out copolymerization reaction with a plurality of other monomers; the epoxy group can react with hydroxyl, amino, carboxyl or acid anhydride to introduce more functional groups. By this reaction, an acrylate group is introduced to the active amino group of epsilon-polylysine, thereby imparting the photo-responsive property to the bio-ink.
The invention also provides the application of the biological ink in photocuring 3D printing.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: the preparation method of the epsilon-polylysine derivative biological ink comprises the following specific steps:
dissolving epsilon-polylysine with the molecular weight of 3500-5000 in deionized water at room temperature, stirring to form a clear solution, and preparing into an aqueous solution with the concentration of 10 wt%.
Mixing epsilon-polylysine and glycidyl methacrylate according to the volume ratio of 50: 1-5.
The mixed solution is reacted for 4 to 8 hours at the temperature of 50 to 80 ℃.
The reacted solution was dialyzed against deionized water for 4 days to remove substances not participating in the reaction.
The dialyzed solution was subjected to vacuum freeze-drying to obtain a pale yellow sponge-like solid.
Dissolving the obtained light yellow spongy solid by using deionized water to obtain an aqueous solution of the epsilon-polylysine biological ink.
Adding an ultraviolet initiator LAP (2, 4, 6-trimethylbenzoyl phosphinic acid phenyl lithium) with the mass fraction of 0.1% into an aqueous solution of the epsilon-polylysine biological ink with the concentration of 10 wt%, placing the aqueous solution in a Nova3D printer with the wavelength of 405mm, and printing to obtain a gel model.
Compared with the prior art, the invention has the following specific beneficial effects: the invention adopts natural biological materials, has simple process, quick and controllable reaction, and the epsilon-polylysine hydrogel has no toxicity to receptors, can be decomposed into amino acid by human bodies, and has biodegradability and biocompatibility. The gel forming speed and the mechanical strength can be adjusted by changing the concentration of epsilon-polylysine and adjusting the substitution degree of glycidyl methacrylate. The hydrogel material prepared by the invention can be used as 3D printing biological ink, and is efficiently, stably and safely applied to a3D printing technology.
Drawings
FIG. 1 is a schematic diagram of the molecular structure and printing of the epsilon-polylysine bio-ink prepared by the present invention.
Fig. 2 is a molecular structure of a polylysine polymer grafted with methacrylic groups.
FIG. 3 is a photograph of a gel model printed by 3D in accordance with the present invention in comparison to a CAD designed model.
Detailed Description
In order to make the technical problems, technical solutions and advantageous effects to be solved by the present invention more clearly apparent, the present invention is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Example 1
Weighing 10g of epsilon-polylysine with the molecular weight of 3500-5000-; mixing an epsilon-polylysine aqueous solution and glycidyl methacrylate according to the volume ratio of 50:1, and stirring for 6 hours under the water bath heating condition at 60 ℃; taking out the reacted solution, dialyzing the solution in deionized water with the pH =6-7 for 4 days (the molecular weight cut-off of a dialysis bag is 1000), and performing vacuum freeze drying after dialysis to prepare the glycidyl methacrylate modified epsilon-polylysine bio-ink, wherein the molecular structure and the printing schematic diagram of the epsilon-polylysine bio-ink are shown in figure 1, and the molecular structure of the polylysine polymer grafted with methacrylic acid groups is shown in figure 2.
Dissolving the prepared epsilon-polylysine biological ink powder into deionized water again to obtain a glycidyl methacrylate modified epsilon-polylysine solution with the concentration of 10 wt%; adding ultraviolet initiator LAP with the mass fraction of 0.1% into the solution and stirring to completely dissolve the ultraviolet initiator LAP; and (3) at room temperature, placing the glycidyl methacrylate modified epsilon-polylysine solution added with the photoinitiator in a Nova3D printer with the wavelength of 405mm for printing to obtain the gel model.
The results of the comparison of the printed gel model with the CAD design model are shown in fig. 3.
Example 2
Weighing 10g of epsilon-polylysine with the molecular weight of 3500-5000-; mixing an epsilon-polylysine aqueous solution and glycidyl methacrylate according to the volume ratio of 50:3, and stirring for 6 hours under the water bath heating condition of 55 ℃; taking out the reacted solution, dialyzing the solution in deionized water with the pH =6-7 for 4 days (the molecular weight cut-off of a dialysis bag is 1000), and performing vacuum freeze drying after dialysis to prepare the glycidyl methacrylate modified epsilon-polylysine biological ink; dissolving the prepared epsilon-polylysine biological ink powder into deionized water again to obtain a glycidyl methacrylate modified epsilon-polylysine solution with the concentration of 10 wt%; adding ultraviolet initiator LAP with the mass fraction of 0.1% into the solution and stirring to completely dissolve the ultraviolet initiator LAP; and (3) at room temperature, placing the glycidyl methacrylate modified epsilon-polylysine solution added with the photoinitiator in a Nova3D printer with the wavelength of 405mm, and printing to obtain the gel model.
Example 3
Weighing 10g of epsilon-polylysine with the molecular weight of 3500-5000-; mixing an epsilon-polylysine aqueous solution and glycidyl methacrylate according to the volume ratio of 10:1, and stirring for 6 hours under the water bath heating condition at 70 ℃; taking out the reacted solution, dialyzing the solution in deionized water with the pH =6-7 for 4 days (the molecular weight cut-off of a dialysis bag is 1000), and performing vacuum freeze drying after dialysis to prepare the glycidyl methacrylate modified epsilon-polylysine biological ink; dissolving the prepared epsilon-polylysine biological ink powder into deionized water again to obtain a glycidyl methacrylate modified epsilon-polylysine solution with the concentration of 10 wt%; adding ultraviolet initiator LAP with the mass fraction of 0.1% into the solution and stirring to completely dissolve the ultraviolet initiator LAP; and (3) at room temperature, placing the glycidyl methacrylate modified epsilon-polylysine solution added with the photoinitiator in a Nova3D printer with the wavelength of 405mm for printing to obtain the gel model.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principles of the present invention are intended to be included therein.
Claims (3)
1. The preparation method of the epsilon-polylysine derivative biological ink is characterized in that the biological ink is obtained by the ring-opening addition reaction of an epoxy group on glycidyl methacrylate and an amino group on a side chain of epsilon-polylysine, and the preparation method comprises the following steps:
dissolving epsilon-polylysine in deionized water to obtain a 10 wt% epsilon-polylysine aqueous solution, mixing the epsilon-polylysine aqueous solution with glycidyl methacrylate according to the volume ratio of 50:1-5, and reacting at the temperature of 50-80 ℃ for 4-8 h;
II, performing secondary filtration; dialyzing the reacted solution in deionized water for 4 days to remove substances which do not participate in the reaction;
thirdly, carrying out vacuum freeze drying treatment on the dialyzed solution to obtain a light yellow spongy solid;
dissolving the obtained light yellow spongy solid by using deionized water to obtain an aqueous solution of the epsilon-polylysine biological ink with the concentration of 10 wt%;
and fifthly, adding the ultraviolet initiator with the mass fraction of 0.1 percent into the aqueous solution prepared in the fourth step, and converting the aqueous solution from a liquid state into a gel state under the irradiation of an ultraviolet light source.
2. The method for preparing epsilon-polylysine derivative biological ink as defined in claim 1, wherein the molecular weight of epsilon-polylysine is 3500-5000.
3. Use of the bio-ink prepared by the preparation method of claim 1 as an ink material for photo-curing 3D printing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210025227.6A CN114058011A (en) | 2022-01-11 | 2022-01-11 | Preparation method and application of epsilon-polylysine derivative biological ink |
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| CN202210025227.6A CN114058011A (en) | 2022-01-11 | 2022-01-11 | Preparation method and application of epsilon-polylysine derivative biological ink |
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| CN202210025227.6A Pending CN114058011A (en) | 2022-01-11 | 2022-01-11 | Preparation method and application of epsilon-polylysine derivative biological ink |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115252886A (en) * | 2022-07-30 | 2022-11-01 | 西北大学 | Preparation method of autocatalytic injectable hydrogel dressing for treating bacterial infection |
| WO2023194587A1 (en) * | 2022-04-06 | 2023-10-12 | The University Of Liverpool | Hydrogels |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105238132A (en) * | 2015-10-20 | 2016-01-13 | 中山大学 | Biological ink for 3D printing |
| CN111138682A (en) * | 2019-12-12 | 2020-05-12 | 苏州永沁泉智能设备有限公司 | Fluorescence-labeled biological material and preparation method thereof |
| CN112111072A (en) * | 2020-09-17 | 2020-12-22 | 南京工业大学 | 3D-printable polylysine antibacterial hydrogel and preparation method and application thereof |
| CN113185718A (en) * | 2021-05-19 | 2021-07-30 | 河南工业大学 | PH/temperature double-sensitive type interpenetrating network hydrogel and preparation method thereof |
-
2022
- 2022-01-11 CN CN202210025227.6A patent/CN114058011A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105238132A (en) * | 2015-10-20 | 2016-01-13 | 中山大学 | Biological ink for 3D printing |
| CN111138682A (en) * | 2019-12-12 | 2020-05-12 | 苏州永沁泉智能设备有限公司 | Fluorescence-labeled biological material and preparation method thereof |
| CN112111072A (en) * | 2020-09-17 | 2020-12-22 | 南京工业大学 | 3D-printable polylysine antibacterial hydrogel and preparation method and application thereof |
| CN113185718A (en) * | 2021-05-19 | 2021-07-30 | 河南工业大学 | PH/temperature double-sensitive type interpenetrating network hydrogel and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| HUANG XIAOBO等: "Enhancement of Antibacterial and Mechanical Properties of Photocurable ε‑Poly‑L‑lysine Hydrogels by Tannic Acid Treatment" * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023194587A1 (en) * | 2022-04-06 | 2023-10-12 | The University Of Liverpool | Hydrogels |
| CN115252886A (en) * | 2022-07-30 | 2022-11-01 | 西北大学 | Preparation method of autocatalytic injectable hydrogel dressing for treating bacterial infection |
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Application publication date: 20220218 |