Microenvironment controlled-release functionalized hydrogel, and preparation method and application thereof
A microenvironment and hydrogel technology, applied in the field of biomedical materials, can solve the problems of not being too regulated and not being able to use biomaterials, and achieve the effects of reducing MMP levels, promoting angiogenesis and maturation, and protecting infarcted myocardial tissue
Active Publication Date: 2020-10-09
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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Problems solved by technology
Some biomaterials deliver factors through physical encapsulation and physical combination, which belong to passive diffusion and are less regulated; some through chemical cross-linking, and direct cross-linking may affect the activity of factors; the inventor of this case The fusion expression of the collagen-specific binding domain (CBD) invented earlier does not change the biological activity of the factor, and can also improve the binding force with collagen materials, but its application is limited to collagen materials and cannot be used for biological materials other than collagen materials
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Embodiment 1
[0069] 1. Preparation and characterization of microenvironment controlled release functionalized hydrogel (hereinafter referred to as collagen-GSH hydrogel)
[0070] Such as figure 1 Shown is a schematic diagram of the preparation of the microenvironment controlled release functionalized hydrogel and the drug release process in the rat myocardial infarction area. figure 1 A represents the GST-TIMP-bFGF protein prepared by protein recombination, and B represents the collagen-GSH hydrogel formed by combining GSH to the collagen hydrogel by chemical cross-linking. C represents GST-TIMP-bFGF mixed with collagen-GSH hydrogel. D represents intramyocardial injection of hybrid hydrogels in rats. E indicates that in the microenvironment of myocardial infarction injury, the substrate peptide is cleaved by MMP-2 / 9 to release the specific targeting polypeptide.
[0071] In this example, the collagen gel was obtained from rat tail tendon. GSH and collagen gel were chemically cross-link...
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The invention discloses microenvironment controlled release type functionalized hydrogel as well as a preparation method and an application thereof. The microenvironment controlled release type functional hydrogel is prepared from a GSH modified collagen gel material and GST-TIMP-bFGF protein combined with the GSH modified collagen gel material. The GST-TIMP-bFGF protein is mainly formed by carrying out fusion expression on a GST label and bFGF and inserting an MMP substrate short peptide TIMP between the GST label and the bFGF. According to the invention, GST-TIMP-bFGF is combined with GSH modified collagen gel to form a bFGF modified biological material with high binding force; the product can respond to myocardial infarction microenvironment stimulation, cleave the substrate short peptide to release bFGF and promote angiogenesis, can inhibit MMP activity, promote myocardial infarction cardiac function recovery and relieve myocardial malfunction reconstruction of an infarction part,and can be applied to treatment of myocardial infarction.
Description
technical field [0001] The invention relates to a microenvironment controlled release functionalized hydrogel, in particular to a microenvironment controlled release type GST-TIMP-bFGF protein with high binding force bound to GSH modified functionalized hydrogel and its preparation method , and its application in the preparation of products for treating myocardial infarction belong to the technical field of biomedical materials. Background technique [0002] Myocardial infarction is the main cause of cardiovascular death and disability worldwide. It is an irreversible myocardial injury caused by coronary artery occlusion, ischemia and hypoxia. After myocardial infarction, the up-regulated matrix metalloproteinases (MMPs), especially MMP-2, degrade the extracellular matrix (ECM), reduce the mechanical properties of the tissue, lead to the gradual thinning of the ventricular wall in the infarct area, the overall expansion, and accelerate the deterioration of cardiac function. ...
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IPC IPC(8): C07K19/00A61K38/18A61K9/06A61K47/42A61P9/10
CPCA61K9/0019A61K9/06A61K38/1825A61K47/42A61P9/10C07K14/503C07K14/81C07K2319/23
Inventor 戴建武范彩霞赵燕南
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI