CN102100925A - Preparation method of novel injectable polypeptide hydrogel - Google Patents
Preparation method of novel injectable polypeptide hydrogel Download PDFInfo
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- CN102100925A CN102100925A CN 200910155067 CN200910155067A CN102100925A CN 102100925 A CN102100925 A CN 102100925A CN 200910155067 CN200910155067 CN 200910155067 CN 200910155067 A CN200910155067 A CN 200910155067A CN 102100925 A CN102100925 A CN 102100925A
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Abstract
The invention discloses a preparation method of a novel injectable polypeptide hydrogel. A polypeptide hydrogel bionic scaffold with osteogenic activity is formed by a polypeptide solution with a specific sequence under a condition with a temperature of 37 DEG C and a pH of 7 based on the self-assembly principle. The method has a simple preparation process; the hydrogel has simple and controllable components and high safety, is injectable before complete self-assembly, can perform in-situ self assembly at gaps with any form between bone defects; the hydrogel can be used as a bionic scaffold material to promote bone repair, and after bone growth factors are added, the hydrogel can be used as a carrier to control the release of the growth factors so as to shorten the treatment course. A culture medium can be added into the system as required, and the system can be used as a bionic scaffold for the three-dimensional culture of osteoblasts.
Description
Technical field
The present invention relates to a kind of preparation method of novel injectable polypeptide hydrogel.Especially, relate to a kind of polypeptide hydrogel support that utilizes the self assembly principle to form to have osteogenic activity, this system injectable can fill up the bone defect gap of Any shape, forms the bionical active support of promoting bone regeneration.
Background technology
Tissue engineering is the emerging cross discipline that middle and late stage proposed and set up the eighties in 20th century.The foundation of bone tissue engineer and development are for exploring and seeking ideal osteanagenesis and opened up new research field.Find that from Bagambisa in 1994 osteoblast is selective to material, people are striving to find a kind of timbering material of cell growth preferably always.Bone tissue engineering stent material can be divided into bioactive ceramics, biologically-derived bone holder material, degradable high polymer material etc. by its source at present.Yet the damaged form of bone is often very complicated, especially at oromaxillo-facial region, the alveolar bone that causes as periodontitis is damaged, the bone resorption that cyst, tumor cause, and the irregular gap that produces and congenital bone defect gap etc. all can't prefabricated ideal support models in the jawbone reduction process, seriously restricting the application prospect of bone tissue engineer in stomatology.
The filling material of bone that present domestic clinical oral uses is all monopolized by foreign brand name, as granular bio-oss etc., but costs an arm and a leg, and complicated operation is seriously restricting its applying clinically.Therefore seek to have independent intellectual property right, can fill up the Any shape gap, and the bionical active timbering material of promoting bone regeneration that contacts closely with surrounding tissue is very urgent, this three-dimensional space structure carrier can provide the microenvironment an of the best for adhesion, propagation, growth and the function performance of osteogenic cell, also can provide space and support for the formation of new bone tissue simultaneously.
Present technique is under the newest research results in fields such as biomaterial, biochemistry, cellular elements biology, Clinical Science of Stomatology is guided, synthetic polypeptide with osteogenic activity, be self-assembled into hydrogel support with the hydrone original position under certain condition with osteogenic activity, and because this system injectable, can fill up the bone defect gap of Any shape, form the bionical active support of promoting bone regeneration, and can be used as the release of carrier control skeletal growth factor, promote bone formation, shorten the course of treatment.
Summary of the invention
The object of the present invention is to provide a kind of easy bionical active timbering material of cheap relatively promoting bone regeneration.
The objective of the invention is to be achieved through the following technical solutions: a kind of preparation method of novel injectable polypeptide hydrogel, it is characterized in that, may further comprise the steps:
(1) has polypeptide synthetic of particular sequence.
(2) preparation of polypeptide solution, and mix in certain proportion.
(3) under 37 ℃, PH are 7 condition, just there is hydrogel to form after several minutes.
The present invention has following technique effect, has good bone biocompatibility with bionic bracket material provided by the invention, the growth of energy rapid induction surrounding bone tissue.Do not have immunogenicity, biological degradability is arranged, product is an aminoacid, can be reuptaked utilization.And before fully being self-assembled into hydrogel, have syringeability, thereby but any irregular bone defective region of filling is particularly useful for the damaged treatment of bone that periodontal disease causes.
The specific embodiment
Liquid polypeptide material hydrogel is introduced the damaged bone cavity by injection, after abundant self assembly, form the porous support hydrogel in the injection site, and can load onto somatomedin and other signaling molecule thereon, can form biomimetic scaffolds by traditional controlled release system and Surface Engineering with combining of self assembly.Timbering material can send signal to cell by the specific receptor of cell surface, by cytoskeleton or various signal transduction pathway signal is conducted to Cytoplasm and even nucleus, basic vital movement such as pair cell survival, form, function, metabolism, propagation, differentiation, migration has considerable influence.
Characteristics of the present invention are: more can simulate meticulous biology and natural macromolecular system by the hydrogel that the molecule self assembly forms, because injectable nanometer polypeptide self assembly hydrogel both can be regulated and control various reactions and result from molecular level, avoided again other as the hydrogel of chemistry or physical crosslinking to the potential hazard that body exists, be the biomimetic material of real meaning.Its self assembly condition is simple, and osteogenic activity is arranged, and it is damaged to repair various erose bones.Describe embodiments of the invention below in detail.
Embodiment 1
At first synthetic highly purified polypeptide (Powdered, its aminoacid sequence is respectively RADARADARADARADA, and RADARGDARADARGDA, R are arginine, and A is an alanine, and D is an aspartic acid, and G is a glycine) with osteogenic activity.Polypeptide material is made into the solution (being dissolved in the deionized water of 1ml as the polypeptide of 10mg) of 1% concentration with deionized water, then two kinds of solution are mixed with 1: 1 (volume ratio), drip a small amount of alpha-MEM culture medium solution at last again, be under 7 the condition at 37 ℃, PH, after leaving standstill several minutes, gel forms gradually.So just having obtained the bionical self assembly polypeptide hydrogel material that osteogenic activity is arranged, also is the good bionic bracket material of osteoblast dimensional culture.
Embodiment 2
At first synthetic highly purified polypeptide (Powdered, its aminoacid sequence is respectively RADARADARADARADA, and RADARGDARADARGDA, R are arginine, and A is an alanine, and D is an aspartic acid, and G is a glycine) with osteogenic activity.Polypeptide material is made into the solution (being dissolved in the deionized water of 1ml as the polypeptide of 10mg) of 1% concentration with deionized water, then two kinds of solution are mixed with 1: 1 (volume ratio), with sterile syringe mixed solution is injected erose bone defective region, the original position self assembly forms hydrogel under the inducing of tissue fluid (as blood), promotes the damaged reparation of bone as timbering material.
Embodiment 3
The polypeptide of synthesis of high purity (Powdered, its aminoacid sequence is respectively RADA16, and R is an arginine, and A is an alanine, and D is an aspartic acid) at first.Polypeptide material is made into the solution of 1% concentration with deionized water, adding a certain amount of rhOP-1 again is made into OP-1 polypeptide hydrogel slow-released system and (is dissolved in the deionized water of 1ml as the polypeptide of 10mg, add 2ug rhOP-1 again), be under 7 the condition at 37 ℃, PH, leave standstill after several minutes and form hydrogel, this polypeptide hydrogel system has the OP-1 slow-release function.
The foregoing description is used for the present invention that explains, rather than limits the invention, and in the protection domain of spirit of the present invention and claim, any modification and change to the present invention makes all fall into protection scope of the present invention.
Claims (3)
1. the preparation method of a novel injectable polypeptide hydrogel is characterized in that, may further comprise the steps: (1) has polypeptide synthetic of particular sequence; (2) preparation of polypeptide solution, and mix in certain proportion, can add culture medium, tissue fluid and somatomedin as required; (3) under 37 ℃, PH are 7 condition, just there is hydrogel to form after several minutes.
2. preparation method according to claim 1 is characterized in that: this hydrogel has syringeability before the self assembly fully.
3. preparation method according to claim 1 is characterized in that: add the biomimetic scaffolds that this hydrogel of culture medium can be used as the osteoblast dimensional culture; Be self-assembled to bone defective region gap with the tissue fluid original position, can be used as bionic bracket material and promote the damaged reparation of bone; Add skeletal growth factor, can be used as the release of the carrier control growing factor, promote bone formation, shorten the course of treatment.
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| Application Number | Priority Date | Filing Date | Title |
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| CN200910155067.1A CN102100925B (en) | 2009-12-16 | 2009-12-16 | Preparation method of novel injectable polypeptide hydrogel |
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| CN200910155067.1A CN102100925B (en) | 2009-12-16 | 2009-12-16 | Preparation method of novel injectable polypeptide hydrogel |
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| CN102100925A true CN102100925A (en) | 2011-06-22 |
| CN102100925B CN102100925B (en) | 2014-03-26 |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104984403A (en) * | 2015-06-16 | 2015-10-21 | 南方医科大学珠江医院 | Loading medicine adipose-derived mesenchymal stem cell polypeptide hydrogel support and preparing method thereof |
| US9180094B2 (en) | 2011-10-12 | 2015-11-10 | The Texas A&M University System | High porosity materials, scaffolds, and method of making |
| CN105268021A (en) * | 2015-10-23 | 2016-01-27 | 中国石油大学(华东) | High-strength polypeptide hydrogel preparation method |
| CN106620886A (en) * | 2016-12-09 | 2017-05-10 | 苏州纳贝通环境科技有限公司 | Liquid bracket material for bone repair and preparation method thereof |
| CN109248343A (en) * | 2018-11-20 | 2019-01-22 | 南京汉瑞生物科技有限公司 | A kind of self assembly polypeptide hydrogel bracket and preparation method thereof |
| US10363215B2 (en) | 2013-11-08 | 2019-07-30 | The Texas A&M University System | Porous microparticles with high loading efficiencies |
| 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 |
| CN115944778A (en) * | 2023-02-15 | 2023-04-11 | 大连工业大学 | Injectable bone repair gel and preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1846789A (en) * | 2005-04-14 | 2006-10-18 | 南方医院 | Injected bone repairing material and its prepn and application |
| CN1846790A (en) * | 2005-04-14 | 2006-10-18 | 南方医院 | Injected tissue engineering bone and its constrction and application |
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2009
- 2009-12-16 CN CN200910155067.1A patent/CN102100925B/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9180094B2 (en) | 2011-10-12 | 2015-11-10 | The Texas A&M University System | High porosity materials, scaffolds, and method of making |
| US10363215B2 (en) | 2013-11-08 | 2019-07-30 | The Texas A&M University System | Porous microparticles with high loading efficiencies |
| CN104984403A (en) * | 2015-06-16 | 2015-10-21 | 南方医科大学珠江医院 | Loading medicine adipose-derived mesenchymal stem cell polypeptide hydrogel support and preparing method thereof |
| CN105268021A (en) * | 2015-10-23 | 2016-01-27 | 中国石油大学(华东) | High-strength polypeptide hydrogel preparation method |
| CN106620886A (en) * | 2016-12-09 | 2017-05-10 | 苏州纳贝通环境科技有限公司 | Liquid bracket material for bone repair and preparation method thereof |
| CN109248343A (en) * | 2018-11-20 | 2019-01-22 | 南京汉瑞生物科技有限公司 | A kind of self assembly polypeptide hydrogel bracket and preparation method 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 |
| CN115944778A (en) * | 2023-02-15 | 2023-04-11 | 大连工业大学 | Injectable bone repair gel and preparation method and application thereof |
| CN115944778B (en) * | 2023-02-15 | 2024-08-06 | 大连工业大学 | Injectable bone repair gel and preparation method and application thereof |
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|---|---|
| CN102100925B (en) | 2014-03-26 |
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