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Injectable myocardial tissue engineering product used for treating myocardial infarction

A technology of tissue engineering and myocardial infarction, which is applied in the field of products for the treatment of myocardial infarction, can solve the problems of myocardial infarction products that have not been reported yet, and achieve the effect of increasing the wall thickness of the infarcted area, increasing blood supply, and mild implementation conditions

Inactive Publication Date: 2010-01-06
INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, OPF hydrogel is mainly used in cartilage and bone tissue engineering, but there is no report on products that use it as a biological carrier and carry growth factors to treat myocardial infarction.

Method used

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  • Injectable myocardial tissue engineering product used for treating myocardial infarction
  • Injectable myocardial tissue engineering product used for treating myocardial infarction
  • Injectable myocardial tissue engineering product used for treating myocardial infarction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Embodiment 1: the preparation of OPF

[0044] Dissolve 30 g of polyethylene glycol with a molecular weight of 1000 in 250 ml of toluene, and after azeotropic distillation, dissolve the dry polyethylene glycol in 250 ml of anhydrous dichloromethane. Fumaryl chloride (0.3 mol) and triethylamine were then added dropwise to the polyethylene glycol solution over 5 hours while the reaction flask was maintained at 0°C and stirred at room temperature for 1-2 days to ensure maximum conversion. After the reaction, the solvent was removed by rotary evaporation, after which the product was dissolved in 500 ml ethyl acetate. The solution was filtered to remove the salt formed by chloride ions and triethylamine during the reaction, and the oligomer was recrystallized twice in ethyl acetate. Finally, pure OPF was precipitated in diethyl ether and dried in vacuo (figure 1 ).

[0045] Purified OPF was stored at -20°C and sterilized before use by exposure to ethylene oxide for 16 hours...

Embodiment 2

[0046] Embodiment 2: Histocompatibility detection of OPF hydrogel

[0047] 0.1ml of OPF hydrogel was injected and implanted into the myocardium of S-D rats, and they were sacrificed at 1, 2, and 4 weeks respectively. Two rats were taken each time. After the specimens were taken out, paraffin sections were made for HE staining to observe the inflammatory reaction. One week after the operation, the OPF hydrogel was widely distributed in the myocardial tissue space, and a few inflammatory cells were mixed in between ( figure 2 A); 2 weeks after operation, the OPF hydrogel was partially degraded and surrounded by inflammatory cell infiltration ( figure 2 B); No obvious OPF hydrogel can be seen in the 4-week group after operation, and a small amount of inflammatory cell infiltration can be seen ( figure 2 C).

Embodiment 3

[0048] Example 3 Preparation of OPF Hydrogel Carrying Gelatin Microparticles Loading Pro-angiogenic Growth Factors

[0049] The gelatin microparticles were immersed in a solution of pro-angiogenic growth factors with a pH of 7.4 and incubated at 4°C for 15 hours to form ion complexes of gelatin and pro-angiogenic growth factors. Subsequently, OPF and the cross-linker polyethylene glycol-diacrylate (PEG-DA) were mixed in 300 μl PBS at a weight ratio of 2:1, and mixed with 100 μl gelatin containing 300 ng of one or more pro-angiogenic growth factors Microparticles were mixed with PBS. An equal volume (50 μl) of the thermal radical initiator, 25 mM ammonium persulfate (APS) and 25 mM N,N,N',N'-tetramethylethylenediamine (TEMED) in PBS, was added. After gentle mixing, the liquid product based on OPF hydrogel and pro-angiogenic growth factor for the treatment of myocardial infarction ( image 3 ). Inject the suspension into the myocardial infarction site for 5-10 minutes to form...

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PUM

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Abstract

The invention discloses an injectable myocardial tissue engineering product used for treating myocardial infarction, in particular, the product applies OPF hydrogel as a scaffold and carries one or more different angiogenic growth factors such as bFGF, PDGF-BB, VEGF 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 promote generation of myocardial capillary and arteriola, enhance generation of myofibroblast, 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 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 [0001] The invention belongs to the field of tissue engineering and regenerative medicine, and relates to a myocardial tissue engineering product based on OPF hydrogel and angiogenic growth factor, in particular to a kind of oligoethylene glycol fumarate (OPF) hydrogel as a carrier Products that carry gelatin microparticles loaded with pro-angiogenic growth factors and can be used for the treatment of myocardial infarction. Background of the invention [0002] Coronary artery disease caused by atherosclerosis is the main cause of morbidity and mortality in the world, among which myocardial infarction is the most serious. Although people have made great progress in the treatment of myocardial infarction, myocardial cell regeneration, left ventricular remodeling and cardiac function damage after myocardial infarction are still the main causes of heart failure. [0003] Angiogenesis-promoting factors include VEGF, FGF, PDGF and other families and their subtypes...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L31/06A61L31/16A61K38/18A61K9/00A61P9/10
Inventor 王常勇王海滨郝彤段翠密
Owner INST OF BASIC MEDICAL SCI ACAD OF MILITARY MEDICAL SCI OF PLA
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