A preparation method of functional artificial skin scaffold material

A technology of artificial skin and scaffold material, which is applied in the field of preparation of medical porous materials, can solve the problems that porogens are difficult to completely remove, the porogens are unfavorable for the use of materials, and are not suitable for full-thickness skin culture. Quality, excellent hydrophilicity, the effect of promoting cell adhesion and growth

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

The skin tissue engineering scaffolds commonly used or researched in clinical practice are mostly scaffolds with uniform pore diameter. Although the material is simple to prepare, it is not suitable for the cultivation of full-thickness skin due to the single pore diameter, 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 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 vitro and in vivo characteristics of PCL scaffolds with pore sizegradient fabricated by a centrifugation method.Biomaterials28,1664-1671, 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 iceparti culates.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 24, 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. Tanya J.Levingstone et al. used 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. Levingstone, T.J., Matsiko, A., Dickson, G.R., O'Brien, F.J. & Gleeson, J.P.A biomimetic multi-layered collagen-basedscaffold for osteochondral repair. Acta Biomaterialia 10, 1996-2004, doi: 10.1016 / j.actbio. 2014.01.005 (2014))

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] The mass ratio of solute to solvent is 2:100, put gelatin in deionized water, heat and stir until completely dissolved;

[0047] Then, cool down to 40° C., then add genipin with a mass ratio of 0.5:100 to gelatin, and stir until completely dissolved to obtain a genipin-gelatin solution;

[0048] Pour the genipin-gelatin solution into a special mold, control the liquid depth to 3mm, and let it stand in an environment with a temperature of 20-50°C for 12-24 hours to make it fully cross-linked; then, place it in a vacuum defoaming machine , defoaming at a vacuum of 1000Pa for 0.5-1h;

[0049] Then, fasten the upper cover and place the special mold on the heat exchange surface of the flat heat exchanger to freeze until it is frozen and formed to obtain genipin-gelatin in the form of solid porous structure;

[0050] The above freezing process is controlled according to the following method: the temperature of the heat exchange surface of the plate heat exchanger adopts a st...

Embodiment 2

[0055] Except that the height of the genipin-gelatin solution liquid level to the mold bottom plate is 0.5mm, all the other are the same as in embodiment 1.

[0056] Checked:

[0057] 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.

Embodiment 3

[0059] Except that the height from the liquid level of genipin-gelatin solution to the bottom plate of the mold is 5 mm, the control method of the freezing process is as follows: the temperature of the heat exchange surface of the plate heat exchanger adopts a stepwise cooling method, with -15°C as the starting temperature and -75°C as the starting temperature. End point temperature, keep warm at the initial temperature for 45 minutes, then keep warm every time the temperature drops by 5°C, and keep warm for 30-45 minutes each time;

[0060] All the other are the same as in Example 2.

[0061] Checked:

[0062] The porosity of the obtained product is 87%; 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 21 μm, and the pore diameter of the large pore is 137 μm.

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PUM

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Abstract

The invention discloses a method for preparing a functional artificial skin scaffold material. According to the method, gelatin having a relative molecular mass of over 10000 serving as a main base material, genipin serving as a crosslinking agent and deionized water, distilled water, normal saline, injection water or Ringer solution serving as a solvent are frozen and formed in a special forming mould by a temperature gradient formed in the vertical direction to obtain a porous material. According to the porous material having a skin biotic structure, a honeycomb porous structure is formed inside the material, the pore diameters are gradient from big to small from the lower surface to the upper surface, wherein the pore diameter of the upper surface is 5-70mu m, the pore diameter of the lower surface is 50-200mu m; adjacent holes are communicated. The preparation process is simple and easily controlled and has low manufacture cost; the prepared product has high and stable quality, has a skin simulation structure, and has excellent moisture absorption, biodegradability and biocompatibility.

Description

technical field [0001] The invention relates to a preparation method of a medical porous material, in particular to a preparation method of a functional artificial skin support material. Background technique [0002] Biological graft material is a kind of biomedical material, which usually refers to the material implanted into the human body by surgery for the replacement, repair and reconstruction of tissues and organs, and maintains long-term contact with human tissues, organs and blood. Biomedical implant materials can be classified into biostable, biodegradable and partially biodegradable according to their behavior in living tissues. Among them, the biodegradable and absorbable graft material can not only provide a temporary support or barrier for the body, but also can be removed by degrading into a substance that can be absorbed by the human body after the function is completed, so as to avoid the excretion caused by the long-term existence of foreign matter in the bo...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61L27/22A61L27/56A61L27/58A61L27/60
CPCA61L27/222A61L27/56A61L27/58A61L27/60
Inventor 张元明韩光亭于仁霞左文倩李显波
Owner QINGDAO UNIV
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