CN111821517A - Temperature-sensitive bionic ligament and preparation method thereof - Google Patents
Temperature-sensitive bionic ligament and preparation method thereof Download PDFInfo
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- CN111821517A CN111821517A CN202010653132.XA CN202010653132A CN111821517A CN 111821517 A CN111821517 A CN 111821517A CN 202010653132 A CN202010653132 A CN 202010653132A CN 111821517 A CN111821517 A CN 111821517A
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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
- A61L27/28—Materials for coating prostheses
- A61L27/34—Macromolecular 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
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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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
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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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/02—Methods for coating medical devices
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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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/10—Materials or treatment for tissue regeneration for reconstruction of tendons or ligaments
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Abstract
The invention belongs to the technical field of artificial ligament preparation, and particularly relates to a temperature-sensitive bionic ligament and a preparation method thereof, wherein the temperature-sensitive bionic ligament comprises the following steps: step 1: ligament fiber surface treatment: repeatedly washing ligament fiber in 5% sodium bicarbonate solution, removing oil and fat on surface, and continuously washing with water until pH is 7; step 2: surface grafting of temperature-sensitive polymer: after drying the ligament fiber, soaking the ligament fiber into a monomer solution of a temperature-sensitive polymer to carry out electron irradiation polymerization or ultraviolet polymerization; or immersing the ligament fiber after plasma treatment or ozonization treatment into a monomer solution of a temperature-sensitive polymer to carry out free radical polymerization. The invention utilizes the cell adhesion performance of the temperature-sensitive polymer, grafts the PNIPAAm isothermal temperature-sensitive polymer on the ligament surface, and after entering the human body, the ligament surface has proper hydrophobicity, thereby being beneficial to the uniform adhesion and growth of fibroblast.
Description
Technical Field
The invention belongs to the technical field of artificial ligament preparation, and particularly relates to a temperature-sensitive bionic ligament and a preparation method thereof.
Background
Prosthetic ligaments are materials used to replace biological joint ligaments. During the last 20 years, artificial ligament products, including the company lars, france, have gained widespread use in ligament reconstruction.
After the artificial ligament is implanted, the fibroblasts can be regenerated on the ligament surface, but the fibroblasts can not grow uniformly on the untreated artificial ligament surface. In order to further improve the capability of promoting the regrowth of fibroblasts after the artificial ligament is implanted, artificial ligament developers perform biomimetic treatment on the ligament surface, and introduce collagen to guide the adhesion and growth of the fibroblasts.
Patent publication No. CN1777450A discloses a bionic artificial ligament and a preparation method thereof. After the surface is oxidized, free radical polymerization is carried out in methacrylic acid and styrene sulfonate monomers. After the polymerization is finished, the solution of fibronectin and type I and/or type III collagen is injected. However, this approach is complicated by the fact that after surface peroxidation, free radical polymerization is required and fibronectin and collagen adhere only to the fiber surface via the surface.
Temperature sensitive polymers, such as poly-N-isopropylacrylamide (PNIPAAm), polyethylene glycol methyl ether methacrylate (OEGMA), poly (N, N-diethylacrylamide) (PDEAAm), are temperature sensitive, hydrophilic at the Lowest Critical Solution Temperature (LCST), and have suitable hydrophobicity above the LCST, which is beneficial for cell adhesion and propagation. By utilizing the temperature-sensitive property of PNIPAAm, professor Teruo Okano of Tokyo Nursery university of Japan performs cell adhesion and propagation above LCST (32 ℃), performs desorption below the LCST temperature to obtain a cell membrane (cell sheet), and then performs in vivo transplantation, which has made a breakthrough in the aspects of myocardial patch and cornea repair at present. CN105288742A discloses that coating PNIPAAm on a polymer matrix can improve biocompatibility and antimicrobial properties, however, this coating method can only be effective in a short period of time, and is easily lost due to friction during surgical operation of ligament and other implants, and cannot achieve long-term effect.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide a temperature-sensitive bionic ligament and a preparation method thereof. According to the invention, the polymer sensitive to temperature is grafted on the surface of ligament fiber, the surface of the polymer is a hydrophilic surface at normal temperature, the surface of the polymer is a hydrophobic surface at 37 ℃, and the surface of the ligament has proper hydrophobicity after the ligament enters a human body, so that uniform adhesion and growth of fibroblasts are facilitated.
The invention provides a preparation method of a temperature-sensitive bionic ligament, which comprises the following steps:
step 1: ligament fiber surface treatment:
repeatedly washing ligament fiber in 5% sodium bicarbonate solution, removing oil and fat on surface, and continuously washing with water until pH is 7;
step 2: surface grafting of temperature-sensitive polymer:
after drying the ligament fiber, soaking the ligament fiber into a monomer solution of a temperature-sensitive polymer to carry out electron irradiation polymerization or ultraviolet polymerization; or immersing the ligament fiber after plasma treatment or ozonization treatment into a monomer solution of a temperature-sensitive polymer to carry out free radical polymerization.
Preferably, the temperature sensitive polymer comprises one or more of PNIPAAm, POEGMA, polyethylene glycol methyl ether methacrylate (OEGMA), poly (N, N-diethylacrylamide) (PDEAAm), poly 3- [ N, N-dimethyl- [2- (2-methylpropan-2-enoyloxy) ethyl ] ammonium ] propane-1-sulfonic acid inner salt.
Preferably, the molecular weight of the temperature-sensitive polymer is 500-50000 daltons.
Preferably, the concentration of the temperature-sensitive polymer monomer solution is 10% -40%.
Preferably, the electron beam energy is 0.25-10MGy, and the vacuum degree is (1-5). times.10 during the electron irradiation polymerization- 4Pa。
Preferably, the reaction time for the electron irradiation polymerization is 20 minutes to 120 minutes.
Preferably, the monomer solution is an aqueous solution or any one of methanol, ethanol and isopropanol solution.
Preferably, the temperature of the baking soda solution for washing the ligament fiber is 50-70 ℃, and more preferably, 60 ℃.
Preferably, after the temperature-sensitive polymer is grafted, the ligament surface water contact angle is 100-120 ℃ at normal temperature, and the contact angle is 40-60 ℃ at 37 ℃.
Another purpose of the invention is to provide a temperature-sensitive bionic ligament prepared by the method.
By the scheme, the invention at least has the following advantages: the invention utilizes the cell adhesion performance of the temperature-sensitive polymer, grafts the PNIPAAm isothermal temperature-sensitive polymer on the ligament surface, and after entering the human body, the ligament surface has proper hydrophobicity, thereby being beneficial to the uniform adhesion and growth of fibroblast.
Drawings
FIG. 1 is a schematic representation of the hydrophilic-hydrophobic transition of a temperature sensitive polymer grafted ligament at ambient and physiological temperatures.
Detailed Description
Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention.
The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.
Example 1
1) Ligament fiber surface treatment: repeatedly washing ligament fiber in 5% sodium bicarbonate solution (60 deg.C) for removing oil from surface, continuously washing with distilled water until pH is 7, and air drying at normal temperature;
2) immersing ligament in 45 wt% PNIPAAm monomer aqueous solution, and performing electron irradiation polymerization with irradiation energy of 0.25MGY and vacuum degree of 1.3 x 10-4Pa, and the irradiation time is 30 min.
Example 2
1) Ligament fiber surface treatment: immersing ligament fiber in 5% sodium bicarbonate solution (60 ℃) for repeated washing to remove grease on the surface, finally continuously washing with distilled water until the pH value is 7, and airing at normal temperature;
2) immersing ligament in 35 wt% PNIPAAm monomer aqueous solution, and polymerizing by electron irradiation with irradiation energy of 0.5MGY and vacuum degree of 1.3 x 10-4Pa, and the irradiation time is 30 min.
Example 3
1) Ligament fiber surface treatment: immersing ligament fiber in 5% sodium bicarbonate solution (60 ℃) for repeated washing to remove grease on the surface, finally continuously washing with distilled water until the pH value is 7, and airing at normal temperature;
2) immersing ligament in 25 wt% PNIPAAm monomer aqueous solution, and polymerizing by electron irradiation with irradiation energy of 0.5MGY and vacuum degree of 1.3 x 10-4Pa, and the irradiation time is 30 min.
Example 4
1) Ligament fiber surface treatment: immersing ligament fiber in 5% sodium bicarbonate solution (60 ℃) for repeated washing to remove grease on the surface, finally continuously washing with distilled water until the pH value is 7, and airing at normal temperature;
2) the ligament fiber surface is treated by plasma for 5 minutes, and then put into 25 percent PNIPAAm monomer aqueous solution (containing 1 percent of alpha-aminoacetophenone initiator) with air removed, and irradiated for 2 hours under an ultraviolet lamp with the wavelength of 320nm under the protection of nitrogen at normal temperature.
Example 5
1) Ligament fiber surface treatment: immersing ligament fiber in 5% sodium bicarbonate solution (60 ℃) for repeated washing to remove grease on the surface, finally continuously washing with distilled water until the pH value is 7, and airing at normal temperature;
2) the ligament fiber surface was plasma treated for 5 minutes, then placed in 25% PNIPAAm monomer isopropanol-water that had been de-aerated (ratio 90: 10) the solution (containing 1% of azobisisobutyronitrile initiator) was reacted at 70 ℃ for 2 hours under nitrogen protection.
The ligament was placed in a cell culture fibroblast culture medium (1 x 10)-6One/well), cultured at 37 degrees for 1 day, and observed for cell adhesion, the results are shown in table 1.
TABLE 1 biological evaluation
| Examples | Ligament cell distribution of ungrafted temperature-sensitive polymers | Ligament cell distribution of grafted temperature-sensitive polymers |
| Example 1 | Substantially cell-free adhesion | Is uniformly distributed |
| Example 2 | Substantially cell-free adhesion | Is uniformly distributed |
| Example 3 | Substantially cell-free adhesion | Is uniformly distributed |
| Example 4 | Substantially cell-free adhesion | Is uniformly distributed |
| Example 5 | Substantially cell-free adhesion | Is uniformly distributed |
As shown in figure 1, the surface of the ligament grafted with the temperature-sensitive polymer is hydrophilic at normal temperature, and the surface is subjected to hydrophilic-hydrophobic conversion at 37 ℃ (physiological temperature), so that a surface easy to adhere to extracellular matrix is produced, and the surface can effectively improve the compatibility of ligament materials and surrounding tissues.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (9)
1. A preparation method of a temperature-sensitive bionic ligament is characterized by comprising the following steps: the method comprises the following steps:
step 1: ligament fiber surface treatment:
repeatedly washing ligament fiber in 5% sodium bicarbonate solution, removing oil and fat on surface, and continuously washing with water until pH is 7;
step 2: surface grafting of temperature-sensitive polymer:
after drying the ligament fiber, soaking the ligament fiber into a monomer solution of a temperature-sensitive polymer to carry out electron irradiation polymerization or ultraviolet polymerization; or immersing the ligament fiber after plasma treatment or ozonization treatment into a monomer solution of a temperature-sensitive polymer to carry out free radical polymerization.
2. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: the temperature-sensitive polymer comprises one or more of PNIPAAm, POEGMA, polyethylene glycol methyl ether methacrylate, poly (N, N-diethyl acrylamide), and poly 3- [ N, N-dimethyl- [2- (2-methylpropane-2-enoyloxy) ethyl ] ammonium ] propane-1-sulfonic acid inner salt.
3. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: the molecular weight of the temperature-sensitive polymer is 500-50000 dalton.
4. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: the concentration of the temperature-sensitive polymer monomer solution is 10-40%.
5. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: in the process of electron irradiation polymerization, the energy of electron beam is 0.25-10MGy, and the vacuum degree is (1-5) x 10-4Pa。
6. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: the reaction time of the electron irradiation polymerization is 20 minutes to 120 minutes.
7. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: the monomer solution is water solution or any one of methanol, ethanol and isopropanol solution.
8. The method for preparing a temperature-sensitive biomimetic ligament according to claim 1, wherein: the temperature for washing ligament fiber by the baking soda solution is 50-70 ℃.
9. A temperature-sensitive biomimetic ligament produced by the method of any one of claims 1-8.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1777450A (en) * | 2003-01-17 | 2006-05-24 | 拉思公司-科学研究与应用试验室 | Biomimetic prosthetic ligament and production method thereof |
| CN103315827A (en) * | 2013-06-25 | 2013-09-25 | 周婕 | Artificial ligament and preparation method thereof |
| CN105828846A (en) * | 2013-11-22 | 2016-08-03 | 拉思公司-科学研究与应用实验室 | Resorbable biomimetic prosthetic ligament |
| US20170157292A1 (en) * | 2014-06-24 | 2017-06-08 | Kaoru WASHIO | Complex of implant and cultured periodontal ligament cell sheet, method for manufacturing the same, and method for using the same |
| KR101775479B1 (en) * | 2016-03-08 | 2017-09-06 | 이화여자대학교 산학협력단 | Bioactive temperature-responsive polymer and its uses as 3-dimensional culture and tissue engineering |
| CN110066787A (en) * | 2019-04-28 | 2019-07-30 | 重庆大学 | It is a kind of can temperature regulation microalgae cell absorption modified substrate and preparation method |
-
2020
- 2020-07-08 CN CN202010653132.XA patent/CN111821517A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1777450A (en) * | 2003-01-17 | 2006-05-24 | 拉思公司-科学研究与应用试验室 | Biomimetic prosthetic ligament and production method thereof |
| CN103315827A (en) * | 2013-06-25 | 2013-09-25 | 周婕 | Artificial ligament and preparation method thereof |
| CN105828846A (en) * | 2013-11-22 | 2016-08-03 | 拉思公司-科学研究与应用实验室 | Resorbable biomimetic prosthetic ligament |
| US20170157292A1 (en) * | 2014-06-24 | 2017-06-08 | Kaoru WASHIO | Complex of implant and cultured periodontal ligament cell sheet, method for manufacturing the same, and method for using the same |
| KR101775479B1 (en) * | 2016-03-08 | 2017-09-06 | 이화여자대학교 산학협력단 | Bioactive temperature-responsive polymer and its uses as 3-dimensional culture and tissue engineering |
| CN110066787A (en) * | 2019-04-28 | 2019-07-30 | 重庆大学 | It is a kind of can temperature regulation microalgae cell absorption modified substrate and preparation method |
Non-Patent Citations (3)
| Title |
|---|
| KIANA MOKHTARINIA等: "Switchable Phase Transition Behavior of Thermoresponsive Substrates for Cell Sheet Engineering", 《JOURNAL OF POLYMER SCIENCE, PART B: POLYMER PHYSICS》 * |
| NORIKO YAMADA等: "Thermo-responsive polymeric surfaces; control of attachment and detachment of cultured cells", 《MAKROMOL. CHEM., RAPID COMMUN.》 * |
| 戴春爱著: "《工科化学》", 31 August 2018, 北京交通大学出版社 * |
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