Preparation method of human skin simulation material with three-dimensional gradient hole structure

A technology of human skin and gradient pores, which is applied in the field of preparation of human skin simulation materials, can solve the problems that porogens are unfavorable to the use of materials, porogens are difficult to completely remove, and are not suitable for full-thickness skin culture, etc., to achieve degradability Good performance, good biocompatibility, and low manufacturing cost

Active Publication Date: 2016-07-27
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. Fabricatingtubular scaffoldswith hara radial pore size gradient by as pinning technique. Biomaterials27,866-874, doi:10.1016 / j.biomaterials.2005.07.06) ; Oh, S.H., Park, I.K., Kim, J.M. & Lee, J.H. Invitro and in vivo characteristics of PCL scaffold with pores size gradient fabricated by acentrifugation method. Biomaterials 28, 1664-1671, doi: 10.1016 / j. biomaterials. The pore size distribution is controlled by adjusting the size of the porogen, but the porogen is difficult to completely remove, and the residual porogen is not good for the later use of the material (Wu, H. et al. .Fabricationofchitosan-g-polycaprolactonecopolymerscaffoldswithgradientporousmicrostructures.MaterialsLetters62,2733-2736,doi:10.1016 / j.matlet.2008.01.029(2008);Zhang,Q.,Lu,H.,Kawazoe,N.&Chen,G.Preparationofcollagenporousscaffoldswithagradientporesizestructureusingiceparticulates.MaterialsLetters107, 280-283, doi: 10.101 6 / j.matlet.2013.05.070(2013); Mao, J.S., Zhao, L.G., Yin, Y.J. & Yao, K.D. Mao et al. placed the sample in a unidirectional heat conduction environment to prepare a double-layer scaffold material. Due to the single pre-freezing temperature, the pore size of the scaffold formed cannot be adjusted, and no gradient pore structure is formed. TanyaJ.Levingstone et al. used layer-by-layer self- The assembly method constructs three-layer gradient bionic cartilage scaffolds, and each layer of scaffolds is prepared by freeze-drying. The preparation of a cartilage scaffold requires three freeze-drying processes, which is time-consuming and laborious (Levingstone, T.J., Matsiko, A., Dickson, G.R., O'Brien, F.J. & Gleeson, J.P. Abiomimetic multi-layered collagen-based scaffold for osteochondral repair. ActaBiomaterialia10, 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

[0061] Add 15 g of sodium alginate into 1000 mL of distilled water and stir at room temperature for 3 h to obtain a sodium alginate or oxidized sodium alginate solution.

[0062] Pour the sodium alginate solution into a special mold, the height from the liquid level of the sodium alginate solution to the bottom plate of the mold is 3 mm; stand for 24 hours for defoaming;

[0063] Then, fasten the upper cover and place the special mold on the top plate of the flat heat exchanger to freeze until it is frozen and formed to obtain sodium alginate or oxidized sodium alginate in the form of solid porous structure;

[0064] 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 stepwise temperature rise method, with -75°C as the initial temperature and -15°C as the end temperature, keep warm at the initial temperature for 45 minutes, and then Warm up once at 5°C, and hold for 30-45 ...

Embodiment 2

[0072] In addition to the raw material being oxidized sodium alginate, 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 initial temperature and -75°C as the end temperature. Keep warm for 45 minutes, then keep warm for every 5°C drop, and keep warm for 30-45 minutes each time;

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

[0074] Checked:

[0075] 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 20 μm, and the pore diameter of the large pore is 200 μm.

[0076] Sodium ion replacement rate: 48.9%

Embodiment 3

[0078] Degassing is placed in a vacuum degassing machine, degassing 0.5h under a vacuum of 1000Pa, cross-linking agent is 25% ferric chloride solution, the control method of the freezing process is: the heat exchange surface temperature of the plate heat exchanger adopts Step 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 5°C, and each time keep warm for 30-45 minutes;

[0079] All the other are the same as in Example 1.

[0080] Checked:

[0081] The porosity of the obtained product is 83%. From the lower surface to the upper surface, the pore diameters of each pore gradually change from large to small, wherein the small pore diameter is 25 μm and the large pore diameter is 200 μm.

[0082] Sodium ion replacement rate: 47.8%

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Abstract

The invention discloses a preparation method of a human skin simulation material with a three-dimensional gradient hole structure. The preparation method is characterized by taking sodium alginate or oxidized sodium alginate of which the relative molecular mass is more than 100,000 as a solute and deionized water, distilled water, normal saline, water for injection or ringer solution as a solvent, forming temperature gradient freezing molding in a dedicated forming die in the vertical direction, and then carrying out a cross-linking reaction, thus obtaining a porous material, wherein the inner part of the porous material is in a honeycomb shape, a plurality of numbers of holes are formed in the porous material, the pore diameter of each hole is respectively in gradient change from large to small from the lower surface to the upper surface, the pore diameter of the upper surface is 5 to 70 mum, the pore diameter of the lower surface of 50 to 200 mum, every two adjacent holes are communicated with each other, and the porous material has a skin simulation structure. According to the preparation method disclosed by the invention, the preparation technology is simple and is easy to control, the preparation cost is low, and a prepared product is good and stable in quality, has the skin simulation structure and has good water absorbing performance, good biodegradability and good 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 human skin simulation material with a three-dimensional gradient pore structure. 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 ba...

Claims

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Application Information

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