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Method for the production of scaffolds for tissue engineering, comprising the use of an anchoring unit, and scaffold produced therewith

A unit, anchoring technology, applied in the field of stent material and stent marking, can solve the problem of not fitting

Inactive Publication Date: 2011-10-19
KONINK PHILIPS ELECTRONICS NV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, this approach has some serious disadvantages, one of which is the fact that the type of marker used must always be determined at the time of scaffold production
In some cases, a given marker may still appear inappropriate, for example for a particular imaging modality or because it elicits an immune response in a particular patient.
In addition, marker bleaching can occur
[0007] Another disadvantage may arise from the persistent in situ release of the respective markers or their metabolites once the scaffold or tissue or organ is implanted, i.e. due to cleavage of the respective binding and / or metabolic degradation of the markers under physiological conditions, For example, through the action of ubiquitous esterases and electrolytes
[0008] Yet another disadvantage may arise from the fact that the scaffold is equipped with labeling reagents prior to cell implantation

Method used

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  • Method for the production of scaffolds for tissue engineering, comprising the use of an anchoring unit, and scaffold produced therewith
  • Method for the production of scaffolds for tissue engineering, comprising the use of an anchoring unit, and scaffold produced therewith
  • Method for the production of scaffolds for tissue engineering, comprising the use of an anchoring unit, and scaffold produced therewith

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0208] Example 1: Labeling of scaffolds with click chemistry comprising covalently bound anchor units.

[0209] Copolymers of ε-caprolactone and α-bromo-ε-caprolactone (or pure α-bromo-ε-caprolactone) were produced as scaffold-forming polymers. This procedure is described in Examples 1.1. - 1.3. The bromine groups of the copolymer are then replaced by azide (N 3 ) group substitution, the latter is the anchor unit of the present invention. This procedure is described in Example 1.4. The copolymers can be subjected to a scaffold forming process, for example by electrospinning before or after the substitution process. Labeling reagents are bound to the anchor units by means of the Staudinger reaction.

[0210] 1.1. Synthesis of α-bromocyclohexanone

[0211] α-Bromocyclohexanone was synthesized according to the following procedure: 49 g (0.306 mol) bromine was added dropwise to a stirred mixture of 30 g (0.306 mol) cyclohexanone and 200 mL distilled water over a period of 5 h...

Embodiment 2

[0224] Embodiment 2: use 18 F-labeled oligonucleotide binding reagent

[0225] The oligonucleotide shown in Figure 5 is used at its 5' end 18 F Labeled according to the method of Kuhnast 2003. 18 F is preferred for positron emission tomography (PET) and scintigraphy (see Table 1). Complementary oligonucleotides are anchored to the scaffold material by methods according to the state of the art and thus serve as anchoring units according to the invention. Methods for binding oligonucleotides to silicate or polymer surfaces are known, for example, from the literature concerning the production of biochips.

Embodiment 3

[0226] Example 3: Labeling of scaffolds by means of Gd-labeled oligonucleotides

[0227] 3.1. DNA-particle-component synthesis

[0228] Au (gold) particles can be prepared as described in the literature (Grabar et al. (1995)). These microparticles are readily modified with oligonucleotides that are functionalized at one end, eg, the 5' end, with an alkanethiol. Here, 1.5 ml (17 nM) of colloidal gold (13nm ?) solution was treated with 460 μl (3.75 μM) of the following species of SH-5'-oligonucleotide-3' for 24 hours (here the sequence was chosen randomly, i.e. any Other sequences are also possible):

[0229] 3'-GCTATCTGGCTATCTGTATCTGTTTTTTTT-5'-SH

[0230] To provide the DNA-gold-component. In this way, anchor units comprising oligonucleotides as binding reagents are obtained. see Figure 10 A description of the process.

[0231] 3.2. Synthesis of DNA-Gd-labeled components

[0232] 1 μmol of amine-modified oligonucleotides (sequence partially complementary to the ...

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Abstract

The present invention relates to a method for the production of scaffold materials and / or scaffolds for tissue and / or organ engineering, said method comprising the addition of at least one anchoring unit for a labelling agent, to at least one scaffold material and / or to at least one scaffold.

Description

technical field [0001] The present invention relates to scaffold materials and scaffolds for tissue engineering and organ engineering. More specifically, the present invention relates to scaffold materials and labeling of scaffolds as contrast agents for medical imaging methods such as CT, MRI, X-Ray, ultrasound, scintigraphy, and the like. Background technique [0002] Tissue engineering is a relatively new discipline that aims to produce tissues or organs in the laboratory that can then be used to repair or replace defective tissues or organs in patients. [0003] In many cases, the tissue or organ is created with the help of a scaffold, which is a three-dimensional matrix that cells use as a basis for their growth and differentiation in vitro or in vivo. Such scaffolds need to mimic the environment in the body and enable cells to influence their own microenvironment. In order to do so, it needs to allow cell attachment and migration, transport and maintain cellular and ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/54A61L31/18A61K49/00A61K49/18A61K51/04A61L27/58A61L31/14
CPCA61K49/0002A61K49/085A61K49/126A61K51/0491A61K51/065A61L27/54A61L27/58A61L31/148A61L31/18A61L2300/44
Inventor D.哈尔特R.库尔特E.彼得斯R.彭特曼D.J.布罗尔R.M.J.N.拉梅里克斯
Owner KONINK PHILIPS ELECTRONICS NV
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