CN107412870A - A kind of collagen-based skin regeneration material with double-layer porous structure and preparation method thereof - Google Patents
A kind of collagen-based skin regeneration material with double-layer porous structure and preparation method thereof Download PDFInfo
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- CN107412870A CN107412870A CN201710230884.3A CN201710230884A CN107412870A CN 107412870 A CN107412870 A CN 107412870A CN 201710230884 A CN201710230884 A CN 201710230884A CN 107412870 A CN107412870 A CN 107412870A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/60—Materials for use in artificial skin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
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- Transplantation (AREA)
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Abstract
The invention discloses a kind of collagen-based skin regeneration material with double-layer porous structure and preparation method thereof, comprise the following steps：(1) collagen is dissolved in acid, prepares certain density collagen solution, using EDC as crosslinking agent, NHS is catalyst, stirring crosslinking；(2) in the collagen system of step (1), while certain density HCl solution and NaOH solution are added, NaCl crystals caused by soda acid reaction in-situ are evenly dispersed in whole collagen system as pore creating material；(3) the porous collagen film obtained by step (2) is fixed on aluminium foil receiver surface, as the reception substrate of electrostatic spinning collagen, passes through collagen layer of the electrostatic spinning process structure with micro-meter scale pore space structure；(4) the double-layer collagen basal lamina material that receiver surface obtains in step (3) is embathed into processing, that is, obtains a kind of collagen-based material with double-layer porous structure.This material can be used for the reparation of skin histology in medical domain.
Description
Technical field
The present invention proposes a kind of preparation method of skin regeneration material, and in particular to has double-layer porous structure to one kind
Collagen-based skin regeneration material and preparation method thereof.
Technical background
Skin is first extraneous of barrier of human body resistance, and it can protect inside of human body tissue and organ to be managed by the external world
Change and maintain normal function when stimulating the invasion and attack with microorganism etc..The defect of skin of defect of skin, especially large area is to face at present
One of most common disease on bed.According to incompletely statistics, China is every year caused by the reasons such as mechanical damage, burn or chemical burn
Skin damage patient populations more than 15,000,000, and wherein need to carry out dermatoplastic patient and be just up to more than 900 ten thousand.With people
Requirement of the class to the general level of the health is improved constantly, and the demand of skin regeneration material will also be increased year by year.Natural skin is from structure
On can be divided into sandwich construction, the specificity structure feature of this natural multilayer order structure and each layer tissue ensure that skin
Various physics and physiologic function (good mechanical property, stable permeance property, and blood vessel, nerve and hair follicle are just
Often distribution etc.).The present invention proposes a kind of double-layer collagen sill with micro-nano porous structure and is used for skin histology reparation, its
Superstructure is made up of the collagen film layer containing nano aperture, and this layer can ensure the intensity of skin regeneration material, plays support
The effect of epithelial layer, and the presence of nanoporous can also meet the needs of oxygen, nutriment and metabolite transmit；Under and
Rotating fields are made up of the collagen scaffold containing um porous, and this layer can ensure the toughness of skin regeneration material, are played corium and are replaced
The effect in generation, and the presence of micron hole can also promote the cell in material to grow into and revascularization.The tool that the present invention obtains
The collagen-based material for having double-layer porous structure can be used for the reparation of clinically damaged skin tissue.
The content of the invention
The shortcomings that it is an object of the invention to overcome prior art, propose a kind of collagen-based skin with double-layer porous structure
Skin repair materials and preparation method thereof.Reparation of this material available for skin histology in medical domain, its preparation technology are simply easy
OK, raw material is cheap and easy to get.In addition, for different skin wounds, by the concentration, volume and die size that change collagen solution
Etc. factor, personalized double-decker collagen-based skin repair timbering material can be prepared.
The purpose of the present invention is achieved through the following technical solutions：
A kind of collagen-based skin regeneration material with double-layer porous structure and preparation method thereof, it is characterised in that including
Following steps：
(1) collagen is dissolved in acetic acid or hydrochloric acid, certain density collagen solution is prepared, then with carbodiimides
(EDC) crosslinking agent is used as, N- maloyls (NHS) are used as catalyst, are added in collagen system and stir according to corresponding ratio
Mix；
(2) in the collagen system obtained by step (1), simultaneously, that certain density HCl solution and NaOH is added dropwise is molten
Liquid, NaCl crystals caused by soda acid reaction in-situ can be evenly dispersed in whole collagen system as nanoscale pore creating material
In, so as to form the collagen film layer with nano aperture structure after air drying；
(3) collagem membrane with nano-porous structure obtained by step (2) is fixed on to the aluminium foil receiver of electrostatic spinning
Surface, as the reception substrate of electrostatic spinning collagen, pass through glue of the electrostatic spinning process structure with micro-meter scale pore space structure
Former layer；
(4) the double-layer collagen basal lamina material that receiver surface obtains in step (3) is embathed with deionized water, freezes place
Reason, that is, obtain a kind of collagen-based skin regeneration material with double-layer porous structure.
Collagenous source described in step (1), (2) and (3) is molten with 0.01-0.1mol/L acetic acid or hydrochloric acid in Cowhells
Liquid prepares collagen solution, and the concentration of collagen is 5.5-7.5mg/mL.
The mass ratio of EDC and collagen is 1 in step (1)：(5.5-6.5), EDC and NHS mass ratio are (1-1.2)：
(0.8-1.2)。
The concentration of HCl and NaOH solution is 0.1mol/L in step (2), and drop speed is 20-35s/ drops.
The condition of electrostatic spinning is in step (3)：Spinning voltage is 10-14kV, and it is 15-25cm to receive distance, and solution pushes away
It is 0.8mL/h to enter speed.
Deionized water is embathed more than 3 times in step (4).
Compared with domestic and international prior art, double-layer collagen base skin regeneration material of the invention has the following advantages that：
(1) double layer material prepared by the present invention, one layer has nano-porous structure, and another layer has um porous structure；
This material has superior physicochemical property and biocompatibility simultaneously.
(2) the collagen-based skin regeneration material of double-decker prepared by the present invention, upper strata nanoporous collagen film layer can be with
Ensure the intensity of skin regeneration material, play a part of supporting epithelial layer, and the presence of nanoporous can also meet oxygen, battalion
Support the demand of material and metabolite transmission；And lower floor's um porous collagen scaffold layer can ensure the tough of skin regeneration material
Property, play a part of corium replacement, and the presence of micron hole can also promote the cell in material to grow into and revascularization.
(3) equipment used in the present invention is simple and easy to get, and cost is relatively low, is advantageous to large-scale production.
Embodiment
In order to be better understood from the present invention, the present invention is described further with reference to embodiment, but the present invention
The scope that the embodiment that claimed scope is not limited to mention represents.
Embodiment 1
(1) collagen is dissolved in 0.05mol/L hydrochloric acid, compound concentration be 6mg/mL collagen solution, then with
Carbodiimides (EDC) is used as crosslinking agent, and N- maloyls (NHS) are used as catalyst, according to collagen：EDC：NHS=6:1:1
Ratio be added in collagen system and stir, carry out cross-linking reaction；
(2) during step (1) collagen system stirs, simultaneously, 0.1mol/L HCl solution and NaOH is added dropwise
Solution, drop speed is 25s/ drops.NaCl crystals caused by soda acid reaction in-situ can equably divide as nanoscale pore creating material
It is dispersed in whole collagen system, the collagen system fully reacted is poured into mould and air-dries film forming；
(3) collagem membrane with nano-porous structure obtained by step (2) is fixed on to the aluminium foil receiver of electrostatic spinning
Surface, as the reception substrate of electrostatic spinning collagen, the spinning condition is controlled to be：Spinning voltage is 14kV, and it is 20cm to receive distance,
Solution fltting speed is 0.8mL/h, passes through collagen layer of the electrostatic spinning process structure with micro-meter scale pore space structure；
(4) the double-layer collagen basal lamina material that receiver surface obtains in step (3) is embathed 5 times with deionized water, freezed
Drying process, that is, obtain a kind of collagen-based skin regeneration material with double-layer porous structure.
Embodiment 2
(1) collagen is dissolved in 0.1mol/L hydrochloric acid, compound concentration is 7mg/mL collagen solution, then with carbon
Change diimine (EDC) and be used as crosslinking agent, N- maloyls (NHS) are used as catalyst, according to collagen：EDC：NHS=6:1:1
Ratio is added in collagen system and stirred, and carries out cross-linking reaction；
(2) during step (1) collagen system stirs, simultaneously, 0.1mol/L HCl solution and NaOH is added dropwise
Solution, drop speed is 30s/ drops.NaCl crystals caused by soda acid reaction in-situ can equably divide as nanoscale pore creating material
It is dispersed in whole collagen system, the collagen system fully reacted is poured into mould and air-dries film forming；
(3) collagem membrane with nano-porous structure obtained by step (2) is fixed on to the aluminium foil receiver of electrostatic spinning
Surface, as the reception substrate of electrostatic spinning collagen, the spinning condition is controlled to be：Spinning voltage is 12kV, and it is 15cm to receive distance,
Solution fltting speed is 0.8mL/h, passes through collagen layer of the electrostatic spinning process structure with micro-meter scale pore space structure；
(4) the double-layer collagen basal lamina material that receiver surface obtains in step (3) is embathed 5 times with deionized water, freezed
Drying process, that is, obtain a kind of collagen-based skin regeneration material with double-layer porous structure.
Claims (7)
- A kind of 1. collagen-based skin regeneration material with double-layer porous structure and preparation method thereof, it is characterised in that including with Lower step：(1) collagen is dissolved in acetic acid or hydrochloric acid, certain density collagen solution is prepared, then with carbodiimides (EDC) crosslinking agent is used as, N- maloyls (NHS) are used as catalyst, are added in collagen system and stir according to corresponding ratio Mix；(2) in the collagen system obtained by step (1), simultaneously, certain density HCl solution and NaOH solution is added dropwise, acid NaCl crystals caused by alkali reaction in-situ can be evenly dispersed in whole collagen system as nanoscale pore creating material, from And the collagen film layer with nano aperture structure is formed after air drying；(3) collagem membrane with nano-porous structure obtained by step (2) is fixed on to the aluminium foil receiver surface of electrostatic spinning, As the reception substrate of electrostatic spinning collagen, pass through collagen layer of the electrostatic spinning process structure with micro-meter scale pore space structure；(4) the double-layer collagen basal lamina material that receiver surface obtains in step (3) is embathed with deionized water, frozen dried, i.e., Obtain a kind of collagen-based skin regeneration material with double-layer porous structure.
- 2. preparation method according to claim 1, it is characterised in that the collagenous source described in step (1), (2) and (3) In Cowhells, collagen solution is prepared with 0.01-0.1mol/L acetic acid or hydrochloric acid solution, the concentration of collagen is 5.5-7.5mg/mL.
- 3. preparation method according to claim 1, it is characterised in that the mass ratio of EDC and collagen is 1 in step (1)： (5.5-6.5), EDC and NHS mass ratio are (1-1.2)：(0.8-1.2).
- 4. preparation method according to claim 1, it is characterised in that the concentration of HCl solution and NaOH solution in step (2) It is 0.1mol/L, drop speed is 20-35s/ drops.
- 5. preparation method according to claim 1, it is characterised in that the condition of electrostatic spinning is in step (3)：Spinning electricity Press as 10-14kV, it is 15-25cm to receive distance, and solution fltting speed is 0.8mL/h.
- 6. according to the preparation method described in claim 1, it is characterised in that deionized water is embathed more than 3 times in step (4).
- 7. collagen-based material prepared by any one of claim 1-6 method.
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| CN201710230884.3A CN107412870A (en) | 2017-04-11 | 2017-04-11 | A kind of collagen-based skin regeneration material with double-layer porous structure and preparation method thereof |
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| CN201710230884.3A CN107412870A (en) | 2017-04-11 | 2017-04-11 | A kind of collagen-based skin regeneration material with double-layer porous structure and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108379664A (en) * | 2018-03-06 | 2018-08-10 | 广东工业大学 | It is a kind of to be used to build two-layer compound holder of full thickness skin and preparation method thereof |
| CN115089766A (en) * | 2022-03-22 | 2022-09-23 | 东华大学 | Method for preparing artificial skin by utilizing electrostatic spinning |
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2017
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108379664A (en) * | 2018-03-06 | 2018-08-10 | 广东工业大学 | It is a kind of to be used to build two-layer compound holder of full thickness skin and preparation method thereof |
| CN115089766A (en) * | 2022-03-22 | 2022-09-23 | 东华大学 | Method for preparing artificial skin by utilizing electrostatic spinning |
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