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Sustained-release system of collagen scaffold loaded with bioactive factors and construction method thereof

A bioactive factor, collagen scaffold technology, used in prostheses, tissue regeneration, coatings, etc., can solve the problems of difficult to control the drug release rate and release amount stably, unstable loaded particles, poor treatment effect, etc. The effect of "burst release" phenomenon, stable and controllable release amount and release rate, and simple construction method

Active Publication Date: 2019-01-18
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Most of the traditional sustained-release strategies use microcapsules and microspheres to coat the protein factors and then load them on the scaffold material, relying on the degradation of the wrapping materials to release the protein factors slowly. However, a major defect of this method is that the loaded particles are unstable and easily released from the scaffold. slip off
In addition, some researchers have blended protein factors with gel materials to construct protein factor sustained-release scaffolds. In this method, since protein factors participate in the preparation process of gel scaffolds, they may undergo organic solvents, freeze-drying, and sterilization. Bacteria and other processes are likely to cause loss of activity
In recent years, the method of layer-by-layer self-assembly has been introduced into the slow-release system of drugs. So far, most of the methods use the interaction of hydrogen bonds, van der Waals forces, hydrophobic interactions, covalent bonds, and hydrophilic interactions. However, the combination of these methods is weak or poor in stability, so that the resulting sustained release system still has defects such as difficult to control the drug release rate and release amount stably, for example, "burst release" will occur, resulting in poor therapeutic effect, or even can cause side effects

Method used

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  • Sustained-release system of collagen scaffold loaded with bioactive factors and construction method thereof
  • Sustained-release system of collagen scaffold loaded with bioactive factors and construction method thereof
  • Sustained-release system of collagen scaffold loaded with bioactive factors and construction method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Example 1 A method for constructing a slow-release system of a collagen scaffold loaded with CBD-bFGF comprises:

[0076] (1) Collagen bundles (the morphology can be referred to figure 2 shown) placed in the CBD-bFGF solution with a concentration of 1ug / ml, 10ug / ml, 20ug / ml, 50ug / ml, and 100ug / ml for 10min~100min (preferably 20min~50min), so that the CBD-bFGF can pass through the specific The recognition function is loaded on the collagen bundle;

[0077] (2) Washing with pure water to remove unbound CBD-bFGF on the collagen bundle after step (1);

[0078] (3) Immerse the collagen bundles completed in step (2) above in PEG solutions with a concentration of 0.1 mg / ml, 1 mg / ml, 3 mg / ml, 5 mg / ml, and 10 mg / ml for 10 min to 100 min (preferably 20 min to 50 min) ), making PEG molecules form a PEG layer on the basis of the above-mentioned support through hydrogen bonding;

[0079] (4) cleaning the collagen bundles completed in step (3) to remove unbound PEG molecules;

...

Embodiment 2

[0087] Example 2 A method for constructing a slow-release system of a collagen scaffold loaded with CBD-bFGF comprises:

[0088] (1) Place the collagen bundles in a CBD-bFGF solution with a concentration of about 10 ug / ml for about 15 minutes;

[0089] (2) Washing with pure water to remove unbound CBD-bFGF on the collagen bundle after step (1);

[0090] (3) Soak the collagen bundles completed in step (2) above for about 10 minutes in a sodium alginate (SA) solution with a concentration of about 2 mg / ml, in which sodium alginate has abundant negative charges, and both CBD-bFGF and collagen have Positive charges can be assembled on the surface of collagen bundles through electrical attraction;

[0091] (4) cleaning the collagen bundles of step (3) to remove unbound sodium alginate molecules;

[0092] (5) Immerse the collagen bundle that has completed step (4) in a collagen solution with a concentration of about 1 mg / ml for about 15 minutes;

[0093] (6) cleaning the collagen ...

Embodiment 3

[0096] Example 3 A method for constructing a slow-release system of a collagen scaffold loaded with CBD-bFGF comprises:

[0097] (1) Place the collagen bundles in a CBD-bFGF solution with a concentration of about 30ug / ml for about 30min;

[0098] (2) Washing with pure water to remove unbound CBD-bFGF on the collagen bundle after step (1);

[0099] (3) Immerse the collagen bundles completed in step (2) above in a heparin (HP) solution with a concentration of about 3 mg / ml for about 30 minutes, wherein the heparin molecules are rich in negative charges and can be combined with positively charged CBD-bFGF and Collagen molecules generate electrostatic attraction, forming a heparin molecular layer on the surface of collagen bundles;

[0100] (4) cleaning the collagen bundles completed in step (3) to remove unbound heparin molecules;

[0101] (5) Immerse the collagen bundles completed in step (4) in a collagen solution with a concentration of about 3 mg / ml for about 30 minutes;

...

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Abstract

The invention discloses a sustained-release system of a collagen scaffold loaded with bioactive factors and a construction method thereof. The construction method comprises the following steps: the collagen scaffold is immersed in a solution containing more than one bioactive factor fused with a collagen-specific binding peptide and then washed to remove the bioactive factor not bound to the collagen scaffold; And placing the collagen scaffold into the polymer solution and reacting; The collagen scaffolds were washed, then impregnated in collagen solution, and then washed. The collagen scaffold loaded with bioactive factor has good biocompatibility, It can realize long-term slow and controllable release of bioactive factors, stable and controllable release amount and release rate, and canput an end to sudden release phenomenon. At the same time, it has simple construction method, good controllability, mild reaction conditions, and has great application potential in biological tissue damage repair, slow and controlled release of drugs and other aspects.

Description

technical field [0001] The invention belongs to the field of biomaterials, and in particular relates to a slow-release system of a collagen scaffold loaded with one or more bioactive factors, its construction method and application. Background technique [0002] The repair of spinal cord injury is still a global medical problem, which brings a heavy burden to individuals, families and society. More and more researchers have proved that the lack of neurotrophic factors at the injury site is one of the important factors hindering injury repair. Therefore, the supplementation of neurochemical factors at the injured site has become one of the breakthroughs in the treatment of spinal cord injury. [0003] At present, the factors that have been found to have neurotrophic effects mainly include brain-derived neurotrophic factor (BDNF), neurotrophic factor NT-3, glial cell-derived neurotrophic factor (GDNF), basic fibroblast growth factor ( bFGF), etc., have the function of protec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/24A61L27/34A61L27/54A61L27/50
CPCA61L27/24A61L27/34A61L27/50A61L27/54A61L2300/414A61L2300/604A61L2300/606A61L2430/32C08L71/02C08L5/04C08L5/10
Inventor 戴建武陈艳艳韩洁
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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