Preparation method of alginate porous material having three-dimensional gradient pore structure

A technology of porous material and alginate, applied in the field of preparation of medical porous materials, can solve the problems of single pore size, time-consuming, easy to cause scars, etc., and achieve the effects of stable product quality, simple preparation process and reduced manufacturing cost.

Active Publication Date: 2016-09-07
QINGDAO UNIV
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  • 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 acentrifugation method.Biomaterials28,1664-1671, 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 the pore size by adjusting the size of the porogens distribution, but the porogen is difficult to completely remove, 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. 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 ic e 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.Biomaterials 24,1067-1074, 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 The pore size of the scaffold cannot be adjusted, and no gradient pore structure is formed. Tanya J.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. , 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

[0062] According to the mass ratio of 1:20, add glycerol into deionized water, stir evenly to make a mixed solution, and set aside;

[0063] Add 15g of sodium alginate into 1000mL of the mixed solution and stir for 0.5-3h to obtain sodium alginate or oxidized sodium alginate solution.

[0064] 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, and stand at room temperature for 24 hours for defoaming;

[0065] 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 or oxidized sodium alginate in the form of solid porous structure;

[0066] 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...

Embodiment 2

[0074] The raw material is oxidized sodium alginate, the defoaming is placed in a vacuum defoaming machine at a vacuum degree of 1000Pa for 2 hours, and the control method of the freezing process is: the temperature of the heat exchange surface of the plate heat exchanger adopts a stepwise cooling method, with - 15°C is the initial temperature, and -75°C is 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 30-45 minutes;

[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 8 μm, and the pore diameter of the large pore is 46 μm.

[0078] Sodium ion replacement rate: 48.9%.

Embodiment 3

[0080] Except that the defoaming is placed in a vacuum defoaming machine at a vacuum of 1000 Pa for 0.5 h, and the crosslinking agent is a 25% ferric chloride solution; the rest are the same as in Example 1.

[0081] Checked:

[0082] 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.

[0083] Sodium ion replacement rate: 47.8%.

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Abstract

The invention discloses a preparation method of an alginate porous material having a three-dimensional gradient pore structure. Sodium alginate or oxidized sodium alginate, which is above 100,000 in relative molecular mass, is taken as a solute, and de-ionized water, distilled water, normal saline, injection water or a Ringer's solution is used as a solvent, so that the structure with interior represented in a honeycombed form is prepared by freezing and forming in a special forming mould through a temperature gradient formed in a perpendicular direction and by conducting a cross-linking reaction; the material comprises a plurality of pores, and from lower surface to upper surface, the diameters of the various pore are in gradient change from large to small, wherein the diameter of the pores in the upper surface is 5-70 [mu]M and the diameter of the pores in the lower surface is 50-200 [mu]M; every two adjuvant pores mutually communicate; and the porous material has a skin bionic structure. The preparation method disclosed by the invention is simple and easy to control and is low in preparation cost; and the prepared product (the porous material) is good and stable in quality and good in water absorbing property, biodegradability and biocompatibility, and the product has the skin bionic structure.

Description

technical field [0001] The invention relates to a preparation method of a medical porous material, in particular to a preparation method of an alginate porous 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 bacteri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/60A61L27/58A61L27/56A61L27/20C08B37/04
CPCA61L27/20A61L27/56A61L27/58A61L27/60A61L2430/40C08B37/0084C08L5/04
Inventor 韩光亭张元明左文倩李显波于仁霞
Owner QINGDAO UNIV
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