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Preparation method of cellular reticular alginate porous material used as artificial skin

A technology of alginate and porous materials, which is applied in the field of preparation of medical porous materials, can solve the problems that the porogen is difficult to completely remove, it is not suitable for full-thickness skin culture, and the use of materials is unfavorable, so as to be beneficial to product quality and reliability. Good degradability and low manufacturing cost

Active Publication Date: 2016-08-10
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 a spinning 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 size gradient fabricated by a centrifugation method.Biomaterials28,11664-167 ,doi: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 by adjusting the size of porogens The pore size distribution, 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. Fabrication of chitosan-g-polycaprolactone copolymer scaffolds with gradient porous microstructures. ,doi:10.1016 / 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 i ce particulates.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.2Biomaterial , 1067-1074, doi:Pii S0142-9612(02)00442-8), Mao et al. placed the sample in a unidirectional heat conduction environment, and prepared a double-layer support material. Due to the single pre-freezing temperature, the formed support The pore size cannot be adjusted, and no gradient pore structure is formed. Tanya J. Levingstone et al. used layer-by-layer self-assembly method to construct a three-layer gradient biomimetic cartilage scaffold. 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. actbio.2014.01.005(2014)

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] According to the mass ratio of 1:20, add polyvinyl alcohol into deionized water, stir evenly to make a mixed solution, and set aside;

[0064] Add 15 g of sodium alginate into 1000 mL of the mixed solution, and stir at room temperature for 3 h to obtain a sodium alginate or oxidized sodium alginate solution.

[0065] 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;

[0066] 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 sodium alginate or oxidized sodium alginate in the form of solid porous structure;

[0067] 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 t...

Embodiment 2

[0074] In addition to the raw material being 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 at the initial temperature Keep warm for 45 minutes, and then keep warm every 5°C, and keep warm for 30-45 minutes each time;

[0075] All the other are the same as in Example 1.

[0076] Checked:

[0077] 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 10 μm, and the pore diameter of the large pore is 108 μm.

[0078] Sodium ion replacement rate: 48.9%.

Embodiment 3

[0080] The defoaming time is 12h, the cross-linking agent is 25% ferric chloride solution, and the control method of the freezing process is: the heat exchange surface temperature of the plate heat exchanger adopts a stepwise cooling method, with -15°C as the initial temperature, - 75°C is the end point temperature, keep warm at the initial temperature for 45 minutes, and keep warm every time the temperature drops by 5°C, and keep warm for 30-45 minutes each time;

[0081] All the other are the same as in Example 1.

[0082] Checked:

[0083] 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 pore diameter of the small pore is 5 μm, and the pore diameter of the large pore is 133 μm.

[0084] Sodium ion replacement rate: 47.8%.

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Abstract

The invention discloses a preparation method of a cellular reticular alginate porous material used as an artificial skin. The preparation method comprises: by taking sodium alginate or oxidized sodium alginate of which the relative molecular mass is more than or equal to 100000 as a solute, and deionized water, distilled water, normal saline, injection water or ringer's solution as a solvent, performing freeze forming by forming a vertical temperature gradient in a special forming mold, and performing crosslinking reaction to obtain a porous material, wherein the inside of the porous material is cellular, the porous material comprises a plurality of pores, the pore diameters of the pores change from big to small in gradient from the lower surface to the upper surface, the pore diameters of the pores on the upper surface are 5-70 mu m, the pore diameters of the pores on the lower surface are 50-200 mu m, and every two adjacent pores are communicated with each other and have skin bionic structures. The preparation method disclosed by the invention is simple, is easy to control and is low in manufacturing cost, and the prepared product is good and stable in quality, has a skin bionic structure, and has good hygroscopicity, 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 honeycomb mesh alginate porous material used as an artificial skin. 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 proper...

Claims

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Application Information

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IPC IPC(8): A61L27/20A61L27/56A61L27/60C08J3/24C08J9/28
CPCA61L27/20A61L27/56A61L27/60C08J3/246C08J9/28C08J2305/04C08L5/04
Inventor 韩光亭张元明于仁霞李显波左文倩
Owner QINGDAO UNIV
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