CN102558304A - Self-assembling peptide, and application of self-assembling peptide to promoting tumor cell to form multicellular spheroid - Google Patents
Self-assembling peptide, and application of self-assembling peptide to promoting tumor cell to form multicellular spheroid Download PDFInfo
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Abstract
The invention discloses self-assembling peptide, and application of the self-assembling peptide to promoting a tumor cell to form a multicellular spheroid. The self-assembling peptide comprises an amino acid segment consisting of 3 to 20 continuous hydrophobic amino acids; specific peptides are connected to an N tail end or a C tail end of the amino acid segment or both the N tail end and the C tail end of the amino acid segment; and the sequence of the specific peptide is GYRGDS, GYRGDSPRGDS, YRGDS, PFSSTKT, SKPPGTSS, YRGDSPRGDS OR PRGDS. The self-assembling peptide can promote the tumor cell to migrate and form the multicellular spheroid. After the peptide forms hydrogel, the microenvironment that the tissue center necrosis which is caused by lack of oxygen and nutrition in in-vivo tumor tissues and extracellular matrix mutually react with each other can be simulated, so the cultured tumor cell can form the multicellular spheroid; and therefore, the growth condition of tumor in a body can be simulated really and a reliable experimental material is provided for various foundational or clinical researches of tumor.
Description
Technical field
But the present invention relates to a kind of self-assembly forms the polypeptide of hydrogel and is promoting tumour cell to form the application in the many cells spheroid.
Background technology
It is active that polypeptide has unique biological.1999; (the National Institutes of Health of NIH; NIH) announced the I clinical trial phase result that two kinds of human immunodeficiency virus (HIV-I) polypeptide vaccine carries out human body; Confirm that this two peptide species vaccine can stimulate body to produce specific antibody and specific immunity cell, and security is preferably arranged.Tsing-Hua University confirms that also one section polypeptide has very strong immunogenicity in the HIV-I membranin.The hepatitis C virus polypeptide vaccine also shows bright development prospect, and the foreign scholar filters out one section polypeptide in hepatitis C virus (HCV) outer membrane protein E2, and it can stimulate body to produce protection antibody.Total institute is known, virus through with host cell on special receptors bind adherent cell, the specific proteases that relies on himself carries out albumen processing and nucleic acid replication.Therefore, if in the peptide storehouse screening can with host cell receptor bonded polypeptide or can with virus protease isoreactivity site bonded polypeptide, these polypeptide just can be used for antiviral treatment so.In addition, polypeptide can also the analog cell factor, and the polypeptide with cytokine activity can be developed into newtype drug.
In sum, polypeptide exists unique biological active, has many-sided purposes, and therefore, in the last few years, life science and material science were also more and more to the research of polypeptide.Wherein, self-assembly polypeptide nano filamentary material (self-assembling peptide nanofiber scaffold SAPNS) has good material because of it especially---cell interface compatibility and BA are more and more paid close attention to.
In the life science field, cultivate for cells in vitro, concern be not only the merisis of cell, their proterties through can keep growth in the body after going down to posterity the time of what is more important.Under many circumstances, (achievement in research that 2D) is obtained and intravital situation also do not meet conventional monolayer culture technique for two-dimentional cell cultures, Two-dimensional.Cell is bred under external two-dimensional environment, and conduction of gene expression of cells, signal and morphological feature all have differently with intravital, and cell can be lost original proterties gradually, causes the scientific research personnel can't obtain reliable experimental.
The cardinal principle that cell in vitro is cultivated is the environment of growth in the analog cell body; This environment can not only let the cell growth go down to posterity; Proterties in the time of can also farthest keeping cell and grow in vivo, and differentiation produces new weave construction, so that study growth course comprehensively.
Tissue is that (Three-dimensional, 3D) structure but often rely on external 2D cell cultures or animal model to three-dimensional when still scientific circles are studied aspects such as human tissue structure, function, pathology at present.Because growing environment has a great difference in the cell culture environment created of external 2D cell cultures and the cell paste,, so utilize external 2D cell cultures to be not enough to reflect the real upgrowth situation of cell like the interaction of cell and cell, cell and matrix etc.Animal model is owing to exist species variation with human body, equally truly antimer inner cell growth characteristics.In the case, the three-dimensional cell culture technique is arisen at the historic moment.Three-dimensional cell culture technique (three dismensional cell culture; TDCC) be in external co-cultivation with the carrier with three-dimensional structure and various different types of cell; Make cell can in the three-dimensional space structure of carrier, move, grow, constitute three-dimensional " cell---carrier complexes " system.
At present; Though the three-dimensional cell cultivated material that sell the home market has improved the cell cultures effect to a certain extent; But because wherein most products are to adopt non-biodegradable material or chemical material to process; Its degraded product and residual organic solvent often pair cell have certain toxic side effect, often cause the cell aseptic inflammation, influence the safety of experimental result and data; Though portioned product is to adopt Biodegradable material to process, some biomaterials contain does not identify composition in a large number, and this brings great risk for clinical study; In addition, it is short that the three-dimensional cell cultured product that a part of biomaterial is processed has the quality guaranteed period, is difficult for the characteristics of preserving and using.
Summary of the invention
For the shortcoming and deficiency that overcomes prior art, but primary and foremost purpose of the present invention is to provide a kind of self-assembly to form the polypeptide of hydrogel.
Another object of the present invention is to provide above-mentioned self-assembly polypeptide promoting tumour cell to form the application in the many cells spheroid.
The object of the invention is realized through following technical proposals:
A kind of self-assembly polypeptide comprises one section amino acid fragment of being made up of 3-20 successive hydrophobic amino acid, at the N-terminal of this amino acid fragment or C-terminal or be connected specific polypeptide with C-terminal at N-terminal simultaneously;
The sequence of said specific polypeptide is GYRGDS (SEQ ID NO.1), GYRGDSPRGDS (SEQ ID NO.2), YRGDS (SEQ ID NO.3), PFSSTKT (SEQ ID NO.4), SKPPGTSS (SEQ ID NO.5), YRGDSPRGDS (SEQ ID NO.6) or PRGDS (SEQ ID NO.7);
Described hydrophobic amino acid is L-Ala (single-letter abbreviation A), Xie Ansuan (V), Isoleucine (I), leucine (L), phenylalanine(Phe) (F), proline(Pro) (P), tyrosine (Y) or glycocoll (G);
The preferred AAAAAA of described amino acid fragment (SEQ ID NO.8), VVVVVV (SEQ ID NO.9), IIIIII (SEQ ID NO.10), LLLLLL (SEQ ID NO.11), FFFFFF (SEQ ID NO.12), PPGPPGPPG (SEQ ID NO.13), FYGFYGFYG (SEQ ID NO.14) or AVILF (SEQ ID NO.15);
Preferably, the N-terminal of said polypeptide carries out acetylize and handles (ac-processing), when perhaps N-terminal being carried out the acetylize processing its C-terminal amidation is handled, promptly-CONH
2
The preferred VVVVVV-GYRGDSPRGDS of described self-assembly polypeptide (SEQ ID NO.16), FFFFFF-GYRGDSPRGDS (SEQ ID NO.17), PPGPPGPPG-YRGDSPRGDS (SEQ ID NO.18) or FYGFYGFYG-YRGDSPRGDS (SEQ ID NO.19).
The sequence of aforementioned polypeptides is artificial design, and is synthetic according to existing general biochemical method.
Above-mentioned polypeptide can promote tumour cell to form the many cells spheroid.Add dissolution with solvents (the mass and size concentration of polypeptide can less than 1%) toward above-mentioned polypeptide; Form water white polypeptide nano fiber water gelating soln (water cut is more than 99%); Can spontaneously be assembled into nanofiber down at certain salt ionic concentration, and further take place crosslinked, the hydrogel (see figure 1) of formation porous network structure; This hydrogel can be used as multiple human cell, especially the three-dimensional space tissue culture support of tumour cell.Tumour cell is put into above-mentioned polypeptide nano fiber water gel to be cultivated; Tumour cell can form the many cells spheroid; Thereby simulate tumour growth in vivo situation more realistically, final purpose is to make the external pharmacological effect test of antitumor drug can react its effect in vivo more accurately.
The present invention has following advantage and effect with respect to prior art:
1, polypeptide of the present invention can make the tumour cell of cultivation in glue, move and form the many cells spheroid after forming hydrogel; The organization center that tumor tissues oxygen and nutrition for want of causes in the analogue body downright bad and and the interaction of extracellular matrix; Thereby reflect tumour growth in vivo situation more realistically, for the various bases or the clinical study of relevant tumour provides reliable experiment material.
2, self-assembly polypeptide of the present invention triggers in water ionic environment or physiological salt solution and forms the three-dimensional stent material gel, and this gel has the following advantages: 1. viscoelasticity is good; 2. be easy to transportation, can be transported to target site through injection technique; 3. degradation property is good, and bioavailability is high, and degraded product is an amino acid monomer, can be used as the source of organism nutritive substance; 4. pair cell or no toxic side effects of tissue and immunoreation; 5. have surface of good activity, structural compatibility and biocompatibility.
Description of drawings
Fig. 1 is the formed hydrogel mode of appearance of the self-assembly polypeptide figure of the embodiment of the invention 1.
Fig. 2 is tumour cell formed many cells spheroid mode of appearance figure in the hydrogel of embodiment 1; Wherein, A-breast cancer cell SK-BR-3 forms the many cells spheroid in hydrogel, and 293 cells of the GFP-transfected gene of B-form many cells spheroid (taking under the fluorescence) in hydrogel, and C-cranial nerve oncocyte Neuro-2a forms the many cells spheroid in hydrogel.
Fig. 3 is tumour cell formed many cells spheroid mode of appearance figure in the hydrogel of embodiment 2; Wherein, A-breast cancer cell SK-BR-3 forms the many cells spheroid in hydrogel, and 293 cells of the GFP-transfected gene of B-form many cells spheroid (taking under the fluorescence) in hydrogel, and C-cranial nerve oncocyte Neuro-2a forms the many cells spheroid in hydrogel.
Fig. 4 is tumour cell formed many cells spheroid mode of appearance figure in the hydrogel of embodiment 3; Wherein, the many cells spheroid that A-breast cancer cell SK-BR-3 forms in hydrogel, the many cells spheroid that B-forms in hydrogel (taking under the fluorescence), the many cells spheroid that C-cranial nerve knurl Neuro-2a forms in hydrogel.
Fig. 5 is tumour cell formed many cells spheroid mode of appearance figure in the hydrogel of embodiment 4; Wherein, the many cells spheroid that A-breast cancer cell SK-BR-3 forms in hydrogel, the many cells spheroid that 293 cells of the GFP-transfected gene of B form in hydrogel (taking under the fluorescence), the many cells spheroid that C-cranial nerve knurl Neuro-2a forms in hydrogel.
Embodiment
Below in conjunction with embodiment and accompanying drawing the present invention is described in further detail, but embodiment of the present invention is not limited thereto.
Embodiment 1
Use self-assembly polypeptide of the present invention and promote tumour cell to form the method for many cells spheroid, may further comprise the steps:
(1) according to document (Hu Chunling, Tang Yinping, Shi Jingni etc. the solid phase synthesis of turtle shell anti-hepatic fibrosis active polypeptide. medical Leader .2011,30 (5): 561-562) the synthetic polypeptide VVVVVV-GYRGDSPRGDS (SEQ ID NO.16) of method.
(2) polypeptides freeze-dry powder of step (1) is last with deionized water dissolving (peptide concentration 1%), polypeptide forms hydrogel solution immediately, uses the membrane filtration degerming of 22um again.
(3) with ultrasonic 30 minutes of polypeptide hydrogel solution, if there is bubble to produce, can centrifugal 1000rpm, 5min is with bubble removal.
(4) (293 cells of GFP-transfected (green fluorescent protein) gene are (available from U.S. Cell Biolabs Inc. company for tumour cell; Down together), breast cancer cell SK-BR-3 is (available from grinding brilliant bio tech ltd in Shanghai; Together following) and cranial nerve oncocyte Neuro-2a (available from visiing Lik-Sang thing Science and Technology Ltd. in Shanghai, down together)), centrifugal removal substratum; With 10% aseptic sucrose solution washed cell; Centrifugal then, remove supernatant, add 10% aseptic sucrose solution again and be mixed with cell suspension (cell density is 1 * 10
6Cells/ml).
(5) with 10% aseptic sucrose solution with the polypeptide hydrogel solution dilution to 0.5% concentration.
(6) with behind cell suspension and the dilution quick mixing of polypeptide hydrogel solution well, add and cultivate in the plate hole, slowly add substratum (RPMI Medium 1640 substratum are bought the company in Invitrogen) along the culture plate hole wall then.
(7) in incubator, leave standstill 30min after, slowly siphon away substratum with the rifle head, add fresh substratum more again, put back to incubator.
(8) leave standstill 30min again, then the operation of repeating step (7).
(9) place 37 ℃ at last, 5%CO
2In the incubator, leave standstill cultivation.Next day inspection cell growing state and substratum color are in time changed liquid.
After cultivating a week, tumour cell is cultivated in hydrogel and is formed many cells spheroid (see Fig. 2, Fig. 2 adopts LEICA DMI 3000B inverted microscope to take) gradually, and this many cells spheroid can be simulated the three-dimensional environment that tumour cell is grown in vivo.
Embodiment 2
Use self-assembly polypeptide of the present invention and promote tumour cell to form the method for many cells spheroid, may further comprise the steps:
(1) according to document (Hu Chunling, Tang Yinping, Shi Jingni etc. the solid phase synthesis of turtle shell anti-hepatic fibrosis active polypeptide. medical Leader .2011,30 (5): 561-562) the synthetic polypeptide FFFFFF-GYRGDSPRGDS (SEQ ID NO.17) of method.
(2) polypeptides freeze-dry powder of step (1) is last with deionized water dissolving (peptide concentration 1%), polypeptide forms hydrogel solution immediately, uses the membrane filtration degerming of 22um again.
(3) with ultrasonic 30 minutes of polypeptide hydrogel solution, if there is bubble to produce, can centrifugal 1000rpm, 5min is with bubble removal.
(4) tumour cell (293 cells of GFP-transfected gene, breast cancer cell SK-BR-3 and cranial nerve oncocyte Neuro-2a); Centrifugal removal substratum; With 10% aseptic sucrose solution washed cell; Centrifugal then, remove supernatant, add 10% aseptic sucrose solution again and be mixed with cell suspension (cell density is 1 * 10
6Cells/ml).
(5) with 10% aseptic sucrose solution with the polypeptide hydrogel solution dilution to 0.5% concentration.
(6) with behind cell suspension and the dilution quick mixing of polypeptide hydrogel solution well, add and cultivate in the plate hole, slowly add substratum (RPMI Medium 1640 substratum are bought the company in Invitrogen) along the culture plate hole wall then.
(7) in incubator, leave standstill 30min after, slowly siphon away substratum with the rifle head, add fresh substratum more again, put back to incubator.
(8) leave standstill 30min again, then the operation of repeating step (7).
(9) place 37 ℃ at last, 5%CO
2In the incubator, leave standstill cultivation.Next day inspection cell growing state and substratum color are in time changed liquid.
After cultivating a week, tumour cell is cultivated in hydrogel and is formed many cells spheroid (see Fig. 3, Fig. 3 adopts LEICA DMI 3000B inverted microscope to take) gradually, and this many cells spheroid can be simulated the three-dimensional environment that tumour cell is grown in vivo.
Embodiment 3
Use self-assembly polypeptide of the present invention and promote tumour cell to form the method for many cells spheroid, may further comprise the steps:
(1) according to document (Hu Chunling, Tang Yinping, Shi Jingni etc. the solid phase synthesis of turtle shell anti-hepatic fibrosis active polypeptide. medical Leader .2011,30 (5): method 561-562) is synthesized polypeptide PPGPPGPPG-YRGDSPRGDS (SEQ ID NO.18).
(2) polypeptides freeze-dry powder of step (1) is last with deionized water dissolving (peptide concentration 1%), polypeptide forms hydrogel solution immediately, uses the membrane filtration degerming of 22um again.
(3) before polypeptide hydrogel solution uses ultrasonic 30 minutes, if there is bubble to produce, can centrifugal 1000rpm, 5min is with bubble removal.
(4) with 10% aseptic sucrose solution with the polypeptide hydrogel solution dilution to 0.5% concentration.
(5) polypeptide hydrogel solution is added in the cultivation plate hole (this process does not produce bubble), slowly add substratum (RPMI Medium 1640 substratum are bought the company in Invitrogen) along the culture plate hole wall then.
(6) culture plate of step (5) is left standstill 30min in incubator after, slowly siphon away substratum with the rifle head, add fresh substratum more again, put back to incubator.
(7) leave standstill 30min again, repeat step (6) step.
(8) tumour cell (293 cells of GFP-transfected gene, breast cancer cell SK-BR-3 and cranial nerve oncocyte Neuro-2a) digestion back is adjusted into suitable concentration (5 * 10 with substratum (RPMI Medium 1640 buys the company in Invitrogen)
4Cells/cm
2), get the 200-300ul cell suspension and slowly add on the colloid along hole wall.
(9) place 37 ℃ at last, 5%CO
2In the incubator, leave standstill cultivation.Next day inspection cell growing state and substratum color are in time changed liquid.
Cultivate after 10 days; Tumour cell moves the water inlet gel gradually and forms the many cells spheroid (sees Fig. 4; Fig. 4 A, 4C adopt LEICADMI 3000B inverted microscope to take; Fig. 4 B adopts Olympus 1X71 inverted microscope to take), this many cells spheroid can be simulated the three-dimensional environment that tumour cell is grown in vivo.
Embodiment 4
Use self-assembly polypeptide of the present invention and promote tumour cell to form the method for many cells spheroid, may further comprise the steps:
(1) according to document (Hu Chunling, Tang Yinping, Shi Jingni etc. the solid phase synthesis of turtle shell anti-hepatic fibrosis active polypeptide. medical Leader .2011,30 (5): method 561-562) is synthesized polypeptide FYGFYGFYG-YRGDSPRGDS (SEQ ID NO.19).
(2) polypeptides freeze-dry powder of step (1) is last with deionized water dissolving (peptide concentration 1%), polypeptide forms hydrogel solution immediately, uses the membrane filtration degerming of 22um again.
(3) before polypeptide hydrogel solution uses ultrasonic 30 minutes, if there is bubble to produce, can centrifugal 1000rpm, 5min is with bubble removal.
(4) with 10% aseptic sucrose solution with the polypeptide hydrogel solution dilution to 0.5% concentration.
(5) polypeptide hydrogel solution is added in the cultivation plate hole (this process does not produce bubble), slowly add substratum (RPMI Medium 1640 substratum are bought the company in Invitrogen) along the culture plate hole wall then.
(6) culture plate of step (5) is left standstill 30min in incubator after, slowly siphon away substratum with the rifle head, add fresh substratum more again, put back to incubator.
(7) leave standstill 30min again, repeat step (6) step.
(8) tumour cell (293 cells of GFP-transfected gene, breast cancer cell SK-BR-3 and cranial nerve oncocyte Neuro-2a) digestion back is adjusted into suitable concentration (5 * 10 with substratum (RPMI Medium 1640 buys the company in Invitrogen)
4Cells/cm
2), get the 200-300ul cell suspension and slowly add on the colloid along hole wall.
(9) place 37 ℃ at last, 5%CO
2In the incubator, leave standstill cultivation.Next day inspection cell growing state and substratum color are in time changed liquid.
Cultivate after 10 days; Tumour cell moves the water inlet gel gradually and forms the many cells spheroid (sees Fig. 5; Fig. 5 A, 5C adopt LEICADMI 3000B inverted microscope to take; Fig. 5 B adopts Olympus 1X71 inverted microscope to take), this many cells spheroid can be simulated the three-dimensional environment that tumour cell is grown in vivo.
The foregoing description is a preferred implementation of the present invention; But embodiment of the present invention is not restricted to the described embodiments; Other any do not deviate from change, the modification done under spirit of the present invention and the principle, substitutes, combination, simplify; All should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (6)
1. self-assembly polypeptide is characterized in that: comprise one section amino acid fragment of being made up of 3-20 successive hydrophobic amino acid, at the N-terminal or the C-terminal of this amino acid fragment or be connected specific polypeptide with C-terminal at N-terminal simultaneously;
The sequence of said specific polypeptide is GYRGDS, GYRGDSPRGDS, YRGDS, PFSSTKT, SKPPGTSS, YRGDSPRGDS or PRGDS.
2. self-assembly polypeptide according to claim 1 is characterized in that: described hydrophobic amino acid is L-Ala, Xie Ansuan, Isoleucine, leucine, phenylalanine(Phe), proline(Pro), tyrosine or glycocoll.
3. self-assembly polypeptide according to claim 1 is characterized in that: described amino acid fragment is AAAAAA, VVVVVV, IIIIII, LLLLLL, FFFFFF, PPGPPGPPG, FYGFYGFYG or AVILF.
4. self-assembly polypeptide according to claim 1 is characterized in that: the N-terminal of said self-assembly polypeptide carries out acetylize to be handled; When perhaps, N-terminal being carried out acetylize and handles to its C-terminal amidation.
5. self-assembly polypeptide according to claim 1 is characterized in that: described self-assembly polypeptide is VVVVVV-GYRGDSPRGDS, FFFFFF-GYRGDSPRGDS, PPGPPGPPG-YRGDSPRGDS or FYGFYGFYG-YRGDSPRGDS.
6. each described self-assembly polypeptide of claim 1-5 is promoting tumour cell to form the application in the many cells spheroid.
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| CN103509088A (en) * | 2013-09-13 | 2014-01-15 | 南开大学 | Novel amphiphilic ionic polypeptide and application thereof in cell culture aspect |
| CN103833833A (en) * | 2012-11-20 | 2014-06-04 | 天津药物研究院 | Self-assembled polypeptide, preparation method and application thereof |
| CN104725475A (en) * | 2015-03-26 | 2015-06-24 | 罗忠礼 | Self-assembly short peptide and application thereof |
| CN107217039A (en) * | 2017-08-01 | 2017-09-29 | 世翱（上海）生物医药科技有限公司 | Tumor tissues 3D cultural methods and nutrient solution |
| CN108517003A (en) * | 2018-04-08 | 2018-09-11 | 南京医科大学 | The plastic factor, hydrogel and pharmaceutical composition |
| CN109316632A (en) * | 2018-11-15 | 2019-02-12 | 北京大学口腔医学院 | A kind of preparation method of left-handed hydrogel material |
| CN110123658A (en) * | 2019-05-22 | 2019-08-16 | 上海璞萃生物科技有限公司 | A kind of supermolecule polypeptide and preparation method thereof with self assembly aggregate structure |
| WO2020141480A1 (en) | 2019-01-04 | 2020-07-09 | Indian Institute Of Technology Bombay | Functional amyloid hydrogels and applications thereof |
| CN113214359A (en) * | 2020-01-21 | 2021-08-06 | 中国人民解放军军事科学院军事医学研究院 | Polypeptide compound, polypeptide self-assembly network material, preparation method and application thereof |
| CN114214280A (en) * | 2021-12-20 | 2022-03-22 | 南开大学 | Method for culturing cell spheres by using self-assembled polypeptide derivative hydrogel, cell spheres and application thereof |
| CN114377202A (en) * | 2021-12-16 | 2022-04-22 | 方向前 | Functional self-assembly miRNA/polypeptide composite hydrogel suitable for cartilage regeneration and preparation method thereof |
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| CN103833833A (en) * | 2012-11-20 | 2014-06-04 | 天津药物研究院 | Self-assembled polypeptide, preparation method and application thereof |
| CN103509088A (en) * | 2013-09-13 | 2014-01-15 | 南开大学 | Novel amphiphilic ionic polypeptide and application thereof in cell culture aspect |
| CN104725475A (en) * | 2015-03-26 | 2015-06-24 | 罗忠礼 | Self-assembly short peptide and application thereof |
| CN104725475B (en) * | 2015-03-26 | 2018-12-18 | 罗忠礼 | A kind of self-assembled short peptide and its application |
| CN107217039A (en) * | 2017-08-01 | 2017-09-29 | 世翱（上海）生物医药科技有限公司 | Tumor tissues 3D cultural methods and nutrient solution |
| CN107217039B (en) * | 2017-08-01 | 2020-03-24 | 世翱（上海）生物医药科技有限公司 | Tumor tissue 3D culture method and culture solution |
| CN108517003A (en) * | 2018-04-08 | 2018-09-11 | 南京医科大学 | The plastic factor, hydrogel and pharmaceutical composition |
| CN108517003B (en) * | 2018-04-08 | 2019-01-29 | 南京医科大学 | The plastic factor, hydrogel and pharmaceutical composition |
| CN109316632B (en) * | 2018-11-15 | 2021-04-20 | 北京大学口腔医学院 | Method for promoting osteogenic differentiation of bone marrow mesenchymal stem cells by using levorotatory hydrogel material |
| CN109316632A (en) * | 2018-11-15 | 2019-02-12 | 北京大学口腔医学院 | A kind of preparation method of left-handed hydrogel material |
| WO2020141480A1 (en) | 2019-01-04 | 2020-07-09 | Indian Institute Of Technology Bombay | Functional amyloid hydrogels and applications thereof |
| CN110123658A (en) * | 2019-05-22 | 2019-08-16 | 上海璞萃生物科技有限公司 | A kind of supermolecule polypeptide and preparation method thereof with self assembly aggregate structure |
| CN110123658B (en) * | 2019-05-22 | 2022-07-15 | 上海璞萃生物科技有限公司 | Supermolecule polypeptide with self-assembly aggregate structure and preparation method thereof |
| CN113214359A (en) * | 2020-01-21 | 2021-08-06 | 中国人民解放军军事科学院军事医学研究院 | Polypeptide compound, polypeptide self-assembly network material, preparation method and application thereof |
| CN114377202A (en) * | 2021-12-16 | 2022-04-22 | 方向前 | Functional self-assembly miRNA/polypeptide composite hydrogel suitable for cartilage regeneration and preparation method thereof |
| CN114377202B (en) * | 2021-12-16 | 2023-01-24 | 方向前 | Functionalized self-assembled miRNA/polypeptide composite hydrogel suitable for cartilage regeneration and preparation method thereof |
| CN114214280A (en) * | 2021-12-20 | 2022-03-22 | 南开大学 | Method for culturing cell spheres by using self-assembled polypeptide derivative hydrogel, cell spheres and application thereof |
| CN114214280B (en) * | 2021-12-20 | 2022-11-29 | 南开大学 | Method for culturing cell spheres by using self-assembled polypeptide derivative hydrogel, cell spheres and application thereof |
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