CN101618235A - Injectable myocardial tissue engineering product applying OPF-based hydrogel as liquid scaffold - Google Patents
Injectable myocardial tissue engineering product applying OPF-based hydrogel as liquid scaffold Download PDFInfo
- Publication number
- CN101618235A CN101618235A CN200810132909A CN200810132909A CN101618235A CN 101618235 A CN101618235 A CN 101618235A CN 200810132909 A CN200810132909 A CN 200810132909A CN 200810132909 A CN200810132909 A CN 200810132909A CN 101618235 A CN101618235 A CN 101618235A
- Authority
- CN
- China
- Prior art keywords
- cell
- opf
- myocardial
- product
- stem cell
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Abstract
The invention discloses an injectable myocardial tissue engineering product applying OPF hydrogel as a liquid scaffold, in particular, the product applies the OPF hydrogel as the scaffold and combines seed cells from different sources, such as embryonic stem cells, mesenchymal stem cells, myocardial cells and the like, and the repair effect of the product on myocardial infarction regions is observed after the product is injected and transplanted into the certain regions of an animal myocardial infarction model. The product built by the scaffold can improve the retention rates and the survival rates of the seed cells, promote regeneration of the myocardial tissues, increase the ventricular wall thickness of the infarction regions, reshape the original ventricle and improve the cardiac function. The product has the characteristic of injectability and is convenient for treatment and operation, thus avoiding the risks brought by the operations such as cardiac arrest and extracorporeal circulation, etc. The invention is simple in operating process and mild in implementation conditions, provides a new product for the myocardial tissue engineering and is of great significance in the development of clinically treating heart diseases by tissue-engineered myocardium.
Description
Technical field
The invention belongs to organizational project and regenerative medicine field, particularly a kind of is the Injectable myocardial tissue engineering product that support is made with low Polyethylene Glycol fumarate (OPF) hydrogel.
Background of invention
The sickness rate and the mortality rate of ischemic heart desease and consequential heart failure rise year by year in the whole world, and cardiovascular system diseases has become among the crowd especially old people's one of major cause of morbidity that causes death, and is one of main difficult problem of current medical profession.At present treatment means comprises medicine, percutaneous coronary intervention, coronary bypass etc., though these means to a certain extent can patients in remission, all is difficult to fundamentally recover number of myocardial cells, improves the heart systolic and diastolic function.The cardiac often needs to carry out organ transplantation late, but because of supplying the transplanted organ limited amount, large quantities of cardiacs are all arranged every year, and treatment loses the therapy apparatus meeting because of can not get effectively.
Myocardial cell is a terminally differentiated cells, and the back cardiac muscle takes place heart infarction can not regenerate, and dead cardiac muscle causes heart failure by the fibrous connective tissue replacement of no contractile function.The endogenous regenerative system is not enough to the cardiomyocyte cell death behind the compensatory myocardial infarction.Drug therapy can delay the natural process of disease, but can not reverse.Therefore, transplanting exogenous cell regeneration cardiac muscle strategy is more and more paid close attention to.The clinical research at zoopery and initial stage shows that cell transplantation can replace the necrotic myocardium cell, improves myocardial infarction district elasticity, stimulates angiogenesis, and the reaction of survival myocardium cell to infarcted region adjusted in the attenuation of restriction infarcted region, prevents that left chamber from enlarging and the progressivity heart failure.Cell transplantation becomes the focus of various countries cardiovascular diseases researcher concern in recent years as a kind of emerging tissue engineering method for the treatment of myocardial infarction.The cell of various sources and different developmental phases is all attempted being transplanted in the healthy and ill heart, comprises the male fetal liver stem cells of c-kit that obtains among fetus myocardial cell, skeleton sarcoplast, medullary cell, endothelial progenitor cells, mescenchymal stem cell, intrinsic cardiac stem cells and mice and human embryo stem cell, clone's the embryo.Wherein embryonic stem cell (ES) has infinitely or almost unlimited self renewal ability and have potentiality to the myocardial cell differentiation and make it become cell source based on the supreme arrogance of a person with great power of the cardiac treatment of cell.
Though a lot of research reports show that injection can make the cardiac function in the various various disease models be restored to simple cell at the heart infarction position, still exists a lot of problems.At first be that the cell number of being detained changes greatly, make that the volume of graft is unpredictable; Next is the mortality of transplanted cells, and the just death in first week of cell that about 90% success is expelled to heart is pointed out in many researchs.Set up simple experimental technique, use the substrate of injectable biomaterial, increase cell delay and survival, will help this application of policies to clinical as a kind of cell transplantation.At present, there are some researches prove that Fibrin Glue, Matrigel, alginate solution can improve the retentivity and the viability of cellular transplant in the infarcted myocardium, the expansion of control infarction and the generation of inducing neovascularity.
Low Polyethylene Glycol fumarate (oligo (poly (ethylene glycol) fumarate) hydrogels (OPF)) is a kind of novel biomaterial with good biocompatibility and biodegradable ability.OPF is the big monomer of a kind of water solublity, alternately is made up of Polyethylene Glycol and fumarate, has good hydrophilic.The OPF hydrogel can carry multiple different cell and somatomedin, is a kind of good syringeability carrier.At present the OPF hydrogel is mainly used in cartilage and bone tissue engineer, is used for development and the exploitation Injectable myocardial tissue engineering product does not appear in the newspapers so far as yet.
Summary of the invention
It is that support makes up syringeability organizational project cardiac muscle product that this product adopts the OPF hydrogel first, it is expelled in the dancing heart ischemic injuries cardiac muscle, improve to improve in the hope of reaching that transplanted cells is detained and survival, repair large tracts of land heart infarction cicatrix and improve the purpose of cardiac function.The invention provides a kind of product of the engineered cardiac muscle of syringeability based on the OPF hydrogel, it is characterized in that providing a kind of new product for cardiac muscle regeneration.
Therefore, first goal of the invention of the present invention provides the method for preparation as the OPF hydrogel of syringeability liquid scaffold, comprising:
(1) preparation of OPF
By Polyethylene Glycol (PEG), fumaryl chloride and triethylamine (mol ratio 1: 0.9: 0.9) one-step method prepared in reaction.Behind the azeotropic distillation, PEG is dissolved in dichloromethane and fumaryl chloride and triethylamine and is dropwise added in several hrs, and reaction flask maintains 0 ℃ simultaneously.Stir 1-2 days then under the room temperature to guarantee maximum conversion.
For the purification oligomer, remove by rotary evaporation and to desolvate, afterwards lysate in ethyl acetate.Solution removes by filter the salt that chloride ion and triethylamine generate in the reaction, oligomer twice in recrystallization in ethyl acetate.Last pure OPF is precipitated out in ether, and vacuum drying (＜1mmHg) obtain powder solid.
The OPF of purification is stored in-20 ℃ and sterilize by being exposed in the oxirane 16 hours before use.
(2) preparation of the OPF hydrogel of syringeability organizational project cardiac muscle product
OPF and cross-linking agent Polyethylene Glycol-diacrylate (PEG-DA) are mixed among the 300 μ lPBS with 2: 1 weight ratio, the heat radical initiator that adds isopyknic (50 μ l), 25mM Ammonium persulfate. (APS) and 25mMN, N, N ', the PBS solution of N '-tetramethylethylenediamine (TEMED).Mixture adds 200 μ l and contains 6.0 * 10 after stirring
6The PBS suspension of cell makes final concentration of cells reach 1 * 10
7Cells/ml.Behind the gentle mixing, be liquid Injectable myocardial tissue engineering product based on the OPF hydrogel.Suspension is expelled to the heart infarction position can becomes glue in 5-10 minute.
Second goal of the invention of the present invention provides the syringeability liquid scaffold OPF hydrogel that utilizes said method prepared, and the further portability of described gel is as the transplanted cells of myocardium seed cell.
The 3rd goal of the invention of the present invention is that described cardiac muscle tissue engineering products is made up of the seed cell of OPF hydrogel and cardiac muscle tissue engineering for the heart infarction treatment provides a kind of new cardiac muscle tissue engineering products.Specifically, provide a kind of improvement to improve transplanted cells delay and survival, repair large tracts of land heart infarction cicatrix and improve the syringeability tissue engineering product of cardiac function, wherein said syringeability tissue engineering product carries the transplanted cells as myocardium seed cell.
In a specific embodiments, described transplanted cells can be any to the effective cell of heart infarction reparation.The for example myocardial cell in the embryonic stem cell in fetus myocardial cell, embryonic stem cell, reconstructed embryo source, mescenchymal stem cell or muscle stem cell directional induction differentiation source, in the not inductive stem cell one or more.(as the mescenchymal stem cell in autologous fat source etc.)
In another embodiment, described myocardial infarction is an acute myocardial infarction, or old myocardial infarction.
The 3rd goal of the invention of the present invention provides described syringeability tissue engineering product or the product of described method preparation is used to the purposes that the medicine of myocardial infarction is treated in the preparation treatment.Wherein, myocardial infarction is an acute myocardial infarction, or old myocardial infarction.
Beneficial effect
The present invention has adopted the OPF hydrogel as the syringeability liquid scaffold, in conjunction with the seed cell regenerating tissues through engineering approaches cardiac muscle of separate sources.This timbering material can improve the retention rate and the survival rate of seed cell, promotes cardiac muscular tissue's regeneration, increases the infarcted region chamber wall thickness, reinvents original ventricle shape, improves cardiac function.This product has the feature of syringeability, is convenient to the treatment operation, avoids the risks that operation brought such as cardiac arrest, extracorporeal circulation.Operating procedure of the present invention is simple, implementation condition is gentle, for cardiac muscle tissue engineering provides a kind of new product, engineered cardiac muscle treatment cardiac disorder clinical is carried out significant.
Description of drawings
Fig. 1. the OPF of solid powdery
The histocompatibility of Fig. 2 .OPF hydrogel detects (HE dyeing)
A.1 all, * 40; B.2 all, * 40; C.3 all, * 40; D.4 all, * 40;
Fig. 3. carry the OPF hydrogel of cell
Fig. 4. rat heart infarction Preparation of model
A. rat coronary artery anterior descending branch ligation;
B. electrocardio diagram ST section is raised the formation of prompting heart infarction;
Fig. 5. echocardiography cardiac function (mitral value level minor axis tangent plane)
The A.OPF hydrogel carries the injection cell group; B.OPF hydrogel injection group; C.PBS carries injection cell; D.PBS injection group
The specific embodiment
Only further describe the present invention now with mode with reference to following non-restrictive example.But should be appreciated that the following examples only as illustration, should be by any way when doing the restriction overall to the invention described above.Unless other explanation is arranged, the traditional molecular biology in embodiments of the invention use this area, cytobiology, tissue engineering or the like.These technology are that the technical staff knows, and detailed explanation is arranged in the literature.Referring to, for example, Lanza, Langer and Vacanti " Principlesof Tissue Engineering " (2006); Atala and Lanza " Methods of Tissue Engineering " (2006).
The preparation of embodiment 1:OPF
With the 30g molecular weight is that 1000 Polyethylene Glycol is dissolved in the 250ml toluene, behind the azeotropic distillation, exsiccant Polyethylene Glycol is dissolved in the anhydrous dichloromethane of 250ml.In 5 hours fumaryl chloride (0.3mol) and triethylamine are dropwise joined in the polyglycol solution then, reaction flask maintains 0 ℃ simultaneously, stirs 1-2 days under the room temperature to guarantee maximum conversion.After the reaction, remove by rotary evaporation and to desolvate, afterwards lysate in the 500ml ethyl acetate.Solution removes by filter the salt that chloride ion and triethylamine generate in the reaction, oligomer twice in recrystallization in ethyl acetate.Last pure OPF is precipitated out in ether, and vacuum drying (＜1mmHg) obtain powder solid (Fig. 1).
The OPF of purification is stored in-20 ℃ and sterilize by being exposed in the oxirane 16 hours before use.
The histocompatibility of embodiment 2:OPF hydrogel detects
OPF hydrogel 0.1ml injection is implanted in the cardiac muscle of S-D rat, respectively at putting to death in 1,2,4 weeks, gets 2 at every turn, carries out paraffin section after the taking-up specimen, makes the situation that inflammatory reaction is observed in HE dyeing.The visible OPF hydrogel of postoperative 1 week section extensively is distributed in the cardiac muscular tissue gap, a little inflammatory cell that mixes (Fig. 2 A) therebetween; The visible OPF hydrogel of postoperative 2 week group is partly degraded, and has inflammatory cell infiltration (Fig. 2 B) on every side; 4 weeks of postoperative are organized and fail to see tangible OPF hydrogel, visible a small amount of inflammatory cell infiltration (Fig. 2 C).
The preparation of the myocardial cell in embodiment 3 mouse embryo stem cells (mES) source
The preparation of mouse embryo fibroblasts feeder layer: put to death the BALB/C mice of pregnant 13d-15d, remove its head and internal organs after getting the embryo under the aseptic condition, use the PBS thorough washing, and be suspended in digestion stage by stage in the 0.25% pancreatin solution after it is shredded.Stop digestion in good time, draw upper strata suspension and centrifugal collecting cell.Trypan blue exclusion method identification of cell vigor, the counting back is with 5 * 10
8Cells/L is resuspended in the H-DMEM culture medium that contains 10%FBS, 37 ℃, 5%CO
2And overnight incubation in the cell culture incubator of saturated humidity.Next day is standby or directly be prepared as feeder layer cells with cell cryopreservation: handle MEF 2.5-3h with the culture medium that contains the 10mg/L ametycin, the PBS thorough washing is to remove residual component.Add the H-DMEM culture medium that contains 10%FBS and be the MEF feeder layer.
Mouse embryo stem cell (mES) increases and is induced to differentiate into myocardial cell: recovery mES is inoculated in standby MEF feeder layer, adds to include 20% hyclone (FBS), 0.1mmol/L beta-mercaptoethanol, 1% non essential amino acid and 1 * 10
6The H-DMEM culture medium of U/L leukaemia inhibitory factor (LIF) is kept cultivation.For keeping its ideal undifferentiated state,, the mES colony goes down to posterity when 60%-70% merges when reaching.The mES cell is induced differentiation after reaching sufficient amount.Trophophase mES takes the logarithm, make single cell suspension through 0.25% trypsinization, place 100mm tissue culture ware through 0.1% gelatin bag quilt, hatch 30min for 37 ℃, because of feeder layer cells adherent within a short period of time, draw the upper strata cell suspension inoculation to another Micro-Organism Culture Dish, this moment, the suspension cell major part was mES.Continue to cultivate 48h, i.e. the EB of visible a plurality of suspensions forms.Next add 0.1% stable vitamin C conditioned medium, continue suspension culture 7d, change liquid every 2d.Behind the suspension culture 7d, respectively EB is seeded to (3/cm on 60mm culture dish
2), and then add this conditioned medium and continue adhere-wall culture, regularly change liquid.Observe EB differentiation situation every day, occur dancing myocardium syncytium behind the 7d, 80%EB is dancing myocardium syncytium behind the 12d.With being single cell suspension behind the 0.1%II Collagen Type VI enzymic digestion cardiac muscle syncytium 1-2h.
The myocardial cell in purification mouse embryo stem cell (mES) source: 9 parts of Percoll liquid and 1 part of 8.5%NaCL are mixed into storage liquid, with the 0.85%NaCL dilution is working concentration, 40.5% for not being divided into the ES cell density of cardiac muscle, and 58.5% is the floating density of myocardial cell in Percoll liquid.The Percoll liquid of 3ml 58.5% is added to the bottom of centrifuge tube, and the Percoll liquid of 3ml 40.5% is added to above 58.5% the Percoll liquid lentamente, and the myocardial cell that 3ml is collected is added to top layer, the centrifugal 20min of 1200g/min lightly again.Collect isolating the 4th, 5 confluent monolayer cells, wash 2 times with PBS, centrifugal removal Percoll liquid, it is resuspended to add complete culture medium.
The myocardial cell fluorescent labeling in mouse embryo stem cell (mES) source: the DAPI fluorescent dye is configured to the storage liquid of 10mg/ml with PBS, get in the cell suspension of 0.1ml adding 20ml, making its final concentration is 50ug/ml, 37 ℃ of lucifuges are hatched 30min, and fluorescence microscope is observed visible cell nuclear staining success down.
Embodiment 4 carries the preparation of the OPF hydrogel of cell
OPF and cross-linking agent Polyethylene Glycol-diacrylate (PEG-DA) are mixed among the 300 μ lPBS with 2: 1 weight ratio, the heat radical initiator that adds isopyknic (50 μ l), 25mM Ammonium persulfate. (APS) and 25mMN, N, N ', the PBS solution of N '-tetramethylethylenediamine (TEMED).Mixture adds 200 μ l and contains 6.0 * 10 after stirring
6The PBS suspension of cell makes the myocardial cell final concentration in mouse embryo stem cell (mES) source reach 1 * 10
7Cells/ml.Behind the gentle mixing, be the liquid Injectable myocardial tissue engineering product based on the OPF hydrogel (Fig. 3).Suspension is expelled to the heart infarction position can becomes glue in 5-10 minute.
Embodiment 5: the selection of animal and the preparation of heart infarction
S-D rat (about 225-300g) is used in experiment, and pentobarbital sodium (40mg/kg body weight) carries out intraperitoneal anesthesia, is connected with animal trace respirator.The row thoracotomy is cut off pericardium, fully exposes heart.At left auricle lower edge 2mm place, prick with 0-7 silk thread seam.Left locular wall loses color after the ligation, and ventricular wall motion weakens (Fig. 4 A).Cardiac monitoring sees that the ST section that I, II lead obviously raises, and shows that coronary artery infarction animal model prepares successfully (Fig. 4 B).
Embodiment 6:OPF hydrogel carries cell and improves the cardiac function detection
18 of S-D rats about 240g are divided at random the OPF hydrogel carries the injection cell group, PBS carries injection cell group, OPF hydrogel injection group, PBS injection group.6 of picked at random S-D rats, male and female are not limit, pentobarbital sodium 35mg/kg body weight intraperitoneal injection of anesthesia.By the rat coronary artery ligation, cause myocardial infarction 30min after, the OPF hydrogel of cell is carried in myocardial ischemia place injection.24 hours pathological examinations point out cell retention rate and survival rate obviously to improve with PBS re-suspended cell injection transplantation group more merely behind the injectable cardiac muscle tissue engineering heart infarction position injection transplantation that the myocardial cell in mouse embryo stem cell (mES) source and aquagel are mixed with, and a large amount of newborn myocardial cell in its 4 all pathological examination prompting mouse embryo stem cells source exists and forms cell with host cell and is connected.Rat heart muscle infarcted region chamber wall thickness obviously improves, and does not find that ventricular aneurysm forms.4 weeks of postoperative are carried out ultrasonic examination to its heart, and cardiac function obviously improves (Fig. 5).
Claims (10)
1. one kind is the preparation method of the syringeability organizational project cardiac muscle product of carrier with the OPF hydrogel, and step comprises:
(1) preparation of OPF:
I. by Polyethylene Glycol (PEG), fumaryl chloride and triethylamine (mol ratio 1: 0.9: 0.9) one-step method prepared in reaction, behind the azeotropic distillation, PEG is dissolved in dichloromethane and fumaryl chloride and triethylamine and is dropwise added in several hrs, reaction flask maintains 0 ℃ simultaneously, stirs 1-2 days then under the room temperature to guarantee maximum conversion;
Ii. for the purification oligomer, remove by rotary evaporation and to desolvate, lysate in ethyl acetate afterwards, solution removes by filter the salt that chloride ion and triethylamine generate in the reaction, oligomer twice in recrystallization in ethyl acetate, last pure OPF is precipitated out in ether, and vacuum drying (＜1mmHg) obtain powder solid;
(2) preparation of the OPF hydrogel of syringeability organizational project cardiac muscle product
Iii.OPF and cross-linking agent Polyethylene Glycol-diacrylate (PEG-DA) are mixed among the PBS with 2: 1 weight ratio, add after isopyknic heat radical initiator mixture stirs, and add the PBS suspension that contains cell and make final concentration of cells reach 1 * 10
7Cells/ml behind the gentle mixing, is the liquid Injectable myocardial tissue engineering product based on the OPF hydrogel, suspension is expelled to the heart infarction position can becomes glue in 5-10 minute.
2. the method described in the claim 1 wherein in step (1), is stored in-20 ℃ and sterilize by being exposed in the oxirane 16 hours before use with the OPF of purification.
3. the method described in the claim 1, wherein in step (2), wherein the heat radical initiator is 25mM Ammonium persulfate. (APS) and 25mMN, N, N ', the PBS solution of N '-tetramethylethylenediamine (TEMED).
4. each described method in the claim 1 to 3 wherein can be crosslinked with the seed cell and the OPF of one or more cardiac muscle tissue engineerings, forms hydrogel.
5. the described method of claim 4, wherein seed cell can be selected the myocardial cell in embryonic stem cell, mescenchymal stem cell or the muscle stem cell directional induction differentiation source in fetus myocardial cell, embryonic stem cell, reconstructed embryo source, in the not inductive stem cell one or more.
6. the cardiac muscle tissue engineering products of the method for claim 1-5 syringeability liquid scaffold prepared, that can be used for treating myocardial infarction.
7. the described product of claim 6, wherein said product is formed by the OPF hydrogel with the seed cell of cardiac muscle tissue engineering.
8. the described product of claim 7, wherein seed cell can be selected the myocardial cell in embryonic stem cell, mescenchymal stem cell or the muscle stem cell directional induction differentiation source in fetus myocardial cell, embryonic stem cell, reconstructed embryo source, in the not inductive stem cell one or more.
9. the described product of claim 6-8 is used to prepare the purposes of the medicine for the treatment of myocardial infarction.
10. the described purposes of claim 9, wherein myocardial infarction is an acute myocardial infarction, or old myocardial infarction.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810132909A CN101618235A (en) | 2008-07-01 | 2008-07-01 | Injectable myocardial tissue engineering product applying OPF-based hydrogel as liquid scaffold |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810132909A CN101618235A (en) | 2008-07-01 | 2008-07-01 | Injectable myocardial tissue engineering product applying OPF-based hydrogel as liquid scaffold |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101618235A true CN101618235A (en) | 2010-01-06 |
Family
ID=41511763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810132909A Pending CN101618235A (en) | 2008-07-01 | 2008-07-01 | Injectable myocardial tissue engineering product applying OPF-based hydrogel as liquid scaffold |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101618235A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102038977A (en) * | 2010-11-29 | 2011-05-04 | 中国人民解放军军事医学科学院基础医学研究所 | Tissue engineered cardiac muscle using OPF (Oligo(Poly(Ethylene Glycol) Fumarate) hydrogel as a carrier and preparation method thereof |
| CN102382797A (en) * | 2011-07-08 | 2012-03-21 | 西安交通大学 | Preparation method of hydrogel scaffold for amplifying human iPS (induced pluripotent stem) cells without differentiating |
| EP2566567A4 (en) * | 2010-05-07 | 2014-11-26 | Univ North Carolina | Method of engrafting cells from solid tissues |
| CN108853147A (en) * | 2018-07-24 | 2018-11-23 | 苏州大学 | A kind of polypeptide nano fiber hydrogel and the preparation method and application thereof being sustained excretion body |
| US10589002B2 (en) | 2014-04-14 | 2020-03-17 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, thermally responsive injectable hydrogel for treatment of ischemic cardiomyopathy |
| US11389569B2 (en) | 2017-04-03 | 2022-07-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, porous, thermally responsive injectable hydrogel as soft tissue defect filler |
| CN115006608A (en) * | 2022-01-25 | 2022-09-06 | 河南省人民医院 | Cerebrovascular coating stent and preparation method thereof |
| US11590162B2 (en) | 2016-10-07 | 2023-02-28 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, antioxidant, thermally responsive injectable hydrogel and uses therefor |
-
2008
- 2008-07-01 CN CN200810132909A patent/CN101618235A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2566567A4 (en) * | 2010-05-07 | 2014-11-26 | Univ North Carolina | Method of engrafting cells from solid tissues |
| CN102038977A (en) * | 2010-11-29 | 2011-05-04 | 中国人民解放军军事医学科学院基础医学研究所 | Tissue engineered cardiac muscle using OPF (Oligo(Poly(Ethylene Glycol) Fumarate) hydrogel as a carrier and preparation method thereof |
| CN102382797A (en) * | 2011-07-08 | 2012-03-21 | 西安交通大学 | Preparation method of hydrogel scaffold for amplifying human iPS (induced pluripotent stem) cells without differentiating |
| CN102382797B (en) * | 2011-07-08 | 2013-04-17 | 西安交通大学 | Preparation method of hydrogel scaffold for amplifying human iPS (induced pluripotent stem) cells without differentiating |
| US10589002B2 (en) | 2014-04-14 | 2020-03-17 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, thermally responsive injectable hydrogel for treatment of ischemic cardiomyopathy |
| US11123454B2 (en) | 2014-04-14 | 2021-09-21 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, thermally responsive injectable hydrogel for treatment of ischemic cardiomyopathy |
| US11590162B2 (en) | 2016-10-07 | 2023-02-28 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, antioxidant, thermally responsive injectable hydrogel and uses therefor |
| US11389569B2 (en) | 2017-04-03 | 2022-07-19 | University of Pittsburgh—of the Commonwealth System of Higher Education | Biodegradable, porous, thermally responsive injectable hydrogel as soft tissue defect filler |
| CN108853147A (en) * | 2018-07-24 | 2018-11-23 | 苏州大学 | A kind of polypeptide nano fiber hydrogel and the preparation method and application thereof being sustained excretion body |
| CN108853147B (en) * | 2018-07-24 | 2021-12-24 | 苏州大学 | Polypeptide nanofiber hydrogel for slowly releasing exosomes and preparation method and application thereof |
| CN115006608A (en) * | 2022-01-25 | 2022-09-06 | 河南省人民医院 | Cerebrovascular coating stent and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101618235A (en) | Injectable myocardial tissue engineering product applying OPF-based hydrogel as liquid scaffold | |
| CN101288779A (en) | Syringeability cardiac muscle tissue engineering products based on thermo-sensitive chitosan hydrogel | |
| Jawad et al. | Myocardial tissue engineering: a review | |
| Kofidis et al. | Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle | |
| EP2322600B1 (en) | Cultured three dimensional tissues and uses thereof | |
| JP4709393B2 (en) | 3D interstitial organization | |
| Zimmermann et al. | Cardiac tissue engineering for replacement therapy | |
| Guo et al. | Transplantation of marrow-derived cardiac stem cells carried in fibrin improves cardiac function after myocardial infarction | |
| ES2540242T3 (en) | 3-D tissue structure | |
| Van Meter Jr et al. | Myoblast transplantation in the porcine model: a potential technique for myocardial repair | |
| Krupnick et al. | A novel small animal model of left ventricular tissue engineering | |
| US20060154365A1 (en) | Cultured three dimensional tissues and uses thereof | |
| CN104189958B (en) | For promoting the preparation method of the multi-functional sticking patch of Properties of Chitosan Fibroin Blend albumen composite nano fiber of regenerating heart tissue and stem cell monitoring | |
| Ravichandran et al. | Minimally invasive cell-seeded biomaterial systems for injectable/epicardial implantation in ischemic heart disease | |
| Dunn et al. | Biomimetic materials design for cardiac tissue regeneration | |
| EP3275471A1 (en) | Three-dimensional structure for cardiac muscular tissue regeneration and manufacturing method therefor | |
| Fedak et al. | Cardiac remodeling and failure: from molecules to man (Part III) | |
| CN104888276B (en) | A kind of cardiac muscle tissue engineering products and its production and use | |
| Portillo Esquivel et al. | Application of cell, tissue, and biomaterial delivery in cardiac regenerative therapy | |
| Munderere et al. | The progress of stem cell therapy in myocardial-infarcted heart regeneration: cell sheet technology | |
| CN102488923A (en) | Tissue-engineered atrioventricular node and construction method and application thereof | |
| CN102038977A (en) | Tissue engineered cardiac muscle using OPF (Oligo(Poly(Ethylene Glycol) Fumarate) hydrogel as a carrier and preparation method thereof | |
| Han et al. | Engineering highly-aligned three-dimensional (3D) cardiac constructs for enhanced myocardial infarction repair | |
| Gu et al. | Tissue engineering and stem cell therapy for myocardial repair | |
| CN110694113B (en) | Preparation method of brain acellular scaffold |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20100106 |