A kind of preparation method of artificial skin support material

A scaffold material and artificial skin technology, applied in the field of preparation of artificial skin scaffold materials, can solve the problems of unfavorable use of porogens for materials, time-consuming, single pore size, etc., and achieve product quality, simple preparation process, and product quality. Stable quality effect

Active Publication Date: 2018-08-24
QINGDAO UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the temperature conduction in the low-temperature refrigerator is along the axis of the pre-freezing model, the pore diameters of porous materials are different along this direction, but the pore size of the longitudinal section is the same. Preparation and performance research of calcium acid-based interpenetrating network membrane materials" studied the alginate solution with a concentration of 2% and pre-frozen in a low-temperature refrigerator at -5°C. The pores in the longitudinal section were uniform and the pore diameter was 100-300 μm. , but due to the single pore size, it is not suitable for the cultivation of full-thickness skin, and it is easy to cause scars when used clinically
Studies have shown that gradient tissue engineering scaffolds with biomimetic skin structures are more conducive to skin regeneration. For skin tissue engineering scaffolds with biomimetic skin structures, research reports are mostly prepared by double-layer or multi-layer composite methods or other methods. It is more time-consuming. For example, Harley and Oh et al. studied the use of rotation / centrifugation technology combined with freeze-drying technology to construct a porous scaffold with a gradient pore structure in the radial direction. The pore size of the scaffold can be adjusted by the rotation speed, but this technology is generally only applicable to the preparation of blood vessels. Tubular scaffold materials are not suitable for constructing other scaffold materials (Harley, B.A., Hastings, A.Z., Yannas, I.V. & Sannino, A. Fabricating tubular scaffolds with a radial pore size gradient by aspinning technique. Biomaterials 27, 866-874, doi:10.1016 / j.biomaterials.2005.07.012(2006); Oh,S.H.,Park,I.K.,Kim,J.M.&Lee,J.H.In vitroand in vivo characteristics of PCL scaffolds with pore size gradientfabricated by a centrifugation method.Biomaterials28,1164-i67 10.1016 / j.biomaterials.2006.11.024 (2007)), Wu, Zhang and Mao et al. used different porogens combined with freeze-drying technology to form gradient pores or double-layer scaffold structures, and controlled the pore size distribution by adjusting the size of the porogens. However, it is difficult to completely remove the porogen, and the residual porogen is unfavorable to the later use of the material (Wu, H. et al. Fabrication of chitosan-g-polycaprolactone copolymer scaffolds with gradient porous microstructures. / j.matlet.2008.01.029(2008); Zhang, Q., Lu, H., Kawazoe, N. & Chen, G. Preparation of collagen porous scaffolds with a gradient pore size structure using icepart iculates.Materials Letters 107,280-283,doi:10.1016 / j.matlet.2013.05.070(2013);Mao,J.S.,Zhao,L.G.,Yin,Y.J.&Yao,K.D.Structure and properties of bilayer chitosan-gelatin scaffolds.Biomaterials 2 1067-1074, doi:Pii S0142-9612(02)00442-8), Mao et al. placed the sample in a one-way thermally conductive environment, and prepared a double-layer scaffold material. Due to the single pre-freezing temperature, the aperture of the scaffold formed It is not regulated and does not form a gradient pore structure. TanyaJ.Levingstone et al. used a layer-by-layer self-assembly method to construct a three-layer gradient biomimetic cartilage scaffold. Each layer of the scaffold was prepared by freeze-drying. The preparation of a cartilage scaffold required three freeze-drying processes, which was time-consuming and laborious. (Levingstone, T.J., Matsiko, A., Dickson, G.R., O'Brien, F.J. & Gleeson, J.P.A biomimetic multi-layered collagen-based scaffold for osteochondral repair. Acta Biomaterialia 10, 1996-2004, doi:10.1016 / j.actbio1.2014.0 .005(2014)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Mix carboxymethyl chitosan and sodium alginate evenly according to the mass ratio of 1:2, set aside;

[0059] According to the mass ratio of solute and solvent of 1:100, the mixture of carboxymethyl chitosan and sodium alginate was dissolved in deionized water, and stirred until completely dissolved to obtain sodium alginate-carboxymethyl chitosan solution ;

[0060] Pour the sodium alginate-carboxymethyl chitosan solution into a special mold, the height from the liquid level of the sodium alginate-carboxymethyl chitosan solution to the bottom plate of the mold is 3mm, and let it stand in an environment of 30°C for 0.5h to Make it fully cross-linked; then, place it in a vacuum degassing machine, and degas it at a vacuum of 1000Pa for 0.5-1h;

[0061] After that, fasten the upper cover and place the special mold on the heat exchange surface of the flat heat exchanger for freezing until it is frozen and formed to obtain sodium alginate-carboxymethyl chitosan or oxidized ...

Embodiment 2

[0067] Except that the raw material is oxidized sodium alginate, the control method of the freezing process is as follows: the heat exchange surface temperature of the plate heat exchanger adopts a stepwise cooling method, with -15°C as the initial temperature and -75°C as the end temperature, and keep warm at the initial temperature 45min, and then keep warm every time the temperature is lowered by 5°C, and each time keep warm for 30-45min;

[0068] All the other are the same as in Example 1.

[0069] Checked:

[0070] The porosity of the obtained product is 86%; from the lower surface to the upper surface, the pore diameters of each pore gradually change from large to small, wherein the pore diameter of the small pore is 13 μm, and the pore diameter of the large pore is 112 μm.

Embodiment 3

[0072] The height from the liquid level of sodium alginate-carboxymethyl chitosan solution to the bottom plate of the mold is 0.5mm; stand in an environment with a temperature of 20°C for 1 hour to make it fully cross-linked; the freezing process control method is: flat plate heat exchange The temperature of the heat exchange surface of the device adopts a stepwise cooling method, with -15°C as the initial temperature and -75°C as the end temperature, keep warm at the initial temperature for 45 minutes, and then keep warm every time the temperature drops by 5°C, and the holding time for each time is 30-45min outside;

[0073] All the other are the same as in Example 1.

[0074] Checked:

[0075] The porosity of the obtained product is 80%; from the lower surface to the upper surface, the pore diameters of each pore gradually change from large to small, wherein the pore diameter of the small pore is 8 μm, and the pore diameter of the large pore is 145 μm.

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Abstract

The invention discloses a preparation method of an artificial skin bracket material. According to the preparation method disclosed by the invention, a mixture of carboxymethyl chitosan and sodium alginate or oxidation sodium alginate in the mass ratio of the carboxymethyl chitosan to the sodium alginate or the oxidation sodium alginate being 1:2 as a solute; distilled water, a Ringer's solution or the like is used as a solvent. In a special shaping die, temperature gradient freeze shaping in the perpendicular direction is performed, so that the artificial skin bracket material of which the inner part adopts a comby porous structure is obtained; from a lower surface to an upper surface, the hole diameters of holes are respectively and gradually decreased in a gradient gradual change manner, wherein the hole diameter of the upper surface is 5-70 [mu]m, and the hole diameter of the lower surface is 50-200 [mu]m, every two adjacent holes are perforated, and the artificial skin bracket material is a porous material adopting a skin bionic structure. The preparation technology is simple and easy to control, the preparation cost is low, and the prepared products are good in quality and stable in quality and adopt skin simulation structures. The artificial skin bracket material has favorable water absorbing property, biodegradability, biocompatibility, antibacterial function, antivirus function and anticoagulated blood function.

Description

technical field [0001] The invention relates to a preparation method of a medical porous material, in particular to a preparation method of an artificial skin support material. Background technique [0002] The choice of biomaterial determines the biocompatibility of the constructed porous scaffold material. Sodium alginate is a natural material extracted from seaweed plants, and is one of the natural biomaterials approved by the US Food and Drug Administration (FDA) for use in medical fields such as tissue engineering. [0003] Sodium alginate, a polysaccharide, has a structure similar to that of the skin dermal matrix component: aminoglycan, and has good biocompatibility. Skin fibroblasts, liver cells, chondrocytes, and osteoblasts are easily absorbed in alginate porous materials. It survives and forms an extracellular matrix. At the same time, sodium alginate also has good film-forming, gelling, hygroscopicity, and barrier bacteria properties, so it is widely used. [0...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/20A61L27/56A61L27/54A61L27/60
CPCA61L27/20A61L27/54A61L27/56A61L27/60C08L5/04C08L5/08
Inventor 张元明韩光亭左文倩于仁霞李显波
Owner QINGDAO UNIV
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