CN107137764A - A kind of preparation method of DOPA structural modification PLA tissue renovation material - Google Patents

A kind of preparation method of DOPA structural modification PLA tissue renovation material Download PDF

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Publication number
CN107137764A
CN107137764A CN201710330845.0A CN201710330845A CN107137764A CN 107137764 A CN107137764 A CN 107137764A CN 201710330845 A CN201710330845 A CN 201710330845A CN 107137764 A CN107137764 A CN 107137764A
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Prior art keywords
solution
dopa
preparation
tissue renovation
structural modification
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CN201710330845.0A
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吴长应
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Wuhu Yangzhan New Material Technology Service Co Ltd
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Wuhu Yangzhan New Material Technology Service Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28Materials for coating prostheses
    • A61L27/34Macromolecular materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2400/00Materials characterised by their function or physical properties
    • A61L2400/18Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/02Methods for coating medical devices
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L2420/00Materials or methods for coatings medical devices
    • A61L2420/06Coatings containing a mixture of two or more compounds

Abstract

A kind of preparation method of DOPA structural modification PLA tissue renovation material, belongs to composite biological material preparation field, and transformation of the way Preparation Method mainly includes:Prepare the amine-modified solution of DOPA, prepare PLA static spinning membrane, the spraying amine-modified solution of DOPA.By DOPA structural modification PLA tissue renovation material made from this method, the cell adhesion and bioactivity of tissue renovation material are further increased.

Description

A kind of preparation method of DOPA structural modification PLA tissue renovation material
Technical field
The invention belongs to composite biological material preparation field, and in particular to a kind of DOPA structural modification PLA tissue repair The preparation method of material.
Background technology
Biomaterial, which is developed so far, has gone through three Main Stages.Since 1980s, with medical treatment, health care And the bio-medical material promoted for the purpose of quality of life etc. achieves quick development, has had more than 50 kinds of implantation instrument quilts Applied to clinic, the engineering material of technology maturation is typically derived from, and with biocompatibility and defective tissue alternative functions, Such as heart artificial blood vessel, joint prosthesis and the artificial kidney for being widely used to clinic.Above-mentioned bio-medical material, with one Universal general character:Biologically inert.I.e. bio-medical material develops followed principle and is to try to acceptor to the different of implantation instrument Thing reaction is preferably minimized.From last century eighties the to the nineties, the emphasis of biomedical materials field is gradually turned by biologically inert To bioactivity and controlled degradation, second generation bio-medical material and product are developed.
Later stage 1990s, third generation biomaterial is accompanied by the foundation of organizational engineering, develops and send out rapidly What exhibition was got up.Using Tissue Engineering Biomaterials support as representative, it combines engineering science and life science principle, careful to plant Born of the same parents, which provide, is adapted to its growth, matrix synthesis and the biology space for playing other functions, overcomes in the past single cell and moves The shortcomings of cell is difficult to survive in plant, matrix synthesis capability is low, the structure for engineered tissue provides cell carrier And structure stand.By bioactive materials and degradation material, the two independent concepts have been combined this kind of bio-medical material Come, molecular modification is carried out in degradation material, the interaction for causing cellular integration plain, induced cell proliferation, differentiation, and The synthesis and assembling of extracellular matrix.But the performance for the biomaterial for being applied to organizational project at present need further to carry It is high, it is impossible to meet the demand of modern medicine.
The content of the invention
In order to solve problems of the prior art, repaiied the invention provides a kind of DOPA structural modification PLA tissue The preparation method of multiple material, further increases the cell adhesion and bioactivity of tissue renovation material.
The present invention uses following technical scheme:
A kind of preparation method of DOPA structural modification PLA tissue renovation material, comprises the following steps:
Step one:By 350mg Gelatins in 60mL water, heating water bath is to 50 DEG C of stirrings to being completely dissolved obtained gelatin Solution;
Step 2:By gelatin solution and 150mg N- hydroxysuccinimides, 191mg 1- ethyls-(3- dimethylaminos Propyl group) phosphinylidyne diimine and 103mg dopamines mixing, in electric heating constant temperature tank 40 DEG C stirring 48 hours after, solution is placed in In bag filter, it is put into the beaker for filling ultra-pure water, is placed in electric heating constant temperature tank and 2-3day is stirred under the conditions of 40 DEG C, and often A ultra-pure water is changed every 8h;
Step 3:The solution remained in bag filter is taken out, is placed in -20 DEG C of household freezers and freezes 8h, then be placed on freeze dryer 48h is dried, adhesiveness gelatin is obtained;
Step 4:Adhesiveness gelatin is made to the 3mg/ml aqueous solution, pH value of water solution is adjusted to 7 with HCl and NaOH, i.e., Obtain the amine-modified solution of DOPA;
Step 5:PLA is dissolved into tetrafluoroethene, compound concentration is 10w/v% solution, stirs 24h under normal temperature Spinning solution is obtained afterwards, static spinning membrane is obtained by electrostatic spinning, normal temperature is placed in 50 DEG C of vacuum drying chambers, is dried to constant weight;
Step 6:By the amine-modified solution even application of DOPA in static spinning membrane surface, and 12h is dried in 37 DEG C of drying boxes Afterwards, rinsed 3 times with phosphate buffer (PBS), produce tissue renovation material.
It is preferred that, the bag filter remaining molecules amount described in step 2 is 10000Da.
It is preferred that, ultrapure water consumption is to cover bag filter in described step two.
It is preferred that, the spinning parameter of electrostatic spinning is in step 5:Copper mesh reception, voltage 12kv, reception are apart from 15cm, stream Fast 0.4ml/h.
It is preferred that, the thickness sprayed in step 6 is 5-30nm.
The beneficial effects of the present invention are:
1) dopamine is a kind of compound in neurohormone, containing abundant ethylamino and catechol active function groups, The surface of any body can be almost sticked to, particularly with organic surface effect more preferably.Gelatin after DOPA is amine-modified sticks Property is higher, and forms on material surface dopamine-gelatin layer of polymerization.The modification of dopamine, is not only increased fixed The content of gelatin, while promoting the adhesion of cell, strengthens the cell compatibility of material surface.
2) substantial amounts of hydroxyl and a small amount of carboxyl and amino are contained in gelatin molecule structure, with extremely strong hydrophily.Cause This, with the amino of dopamine condensation reaction can occur for the carboxyl in gelatin molecule.There are gelatin other synthetic materials can not compare Biocompatibility, degradability and the bioactivity of plan.
3) PLA has good biodegradability, while also having good Bioabsorbable and bio-compatible Property, any environmental issue will not be left after degradation, and in medical field, oneself is considered as most promising degradable macromolecule material Material.
Embodiment
The present invention is described in further detail with reference to embodiments.
Embodiment 1
A kind of preparation method of DOPA structural modification PLA tissue renovation material, comprises the following steps:
Step one:By 350mg Gelatins in 60mL water, heating water bath is to 50 DEG C of stirrings to being completely dissolved obtained gelatin Solution;
Step 2:By gelatin solution and 150mg N- hydroxysuccinimides, 191mg 1- ethyls-(3- dimethylaminos Propyl group) phosphinylidyne diimine and 103mg dopamines mixing, in electric heating constant temperature tank 40 DEG C stirring 48 hours after, solution is placed in In bag filter, described bag filter remaining molecules amount is 10000Da, and bag filter is put into the beaker for filling ultra-pure water, ultrapure Beaker is placed in electric heating constant temperature tank and stirs 2-3day under the conditions of 40 DEG C by water consumption to cover bag filter position, and every 8h changes a ultra-pure water;
Step 3:The solution remained in bag filter is taken out, is placed in -20 DEG C of household freezers and freezes 8h, then be placed on freeze dryer 48h is dried, adhesiveness gelatin is obtained;
Step 4:Adhesiveness gelatin is made to the 3mg/ml aqueous solution, pH value of water solution is adjusted to 7 with HCl and NaOH, i.e., Obtain the amine-modified solution of DOPA;
Step 5:PLA is dissolved into tetrafluoroethene, compound concentration is 10w/v% solution, stirs 24h under normal temperature Spinning solution is obtained afterwards, static spinning membrane is obtained by electrostatic spinning, spinning parameter is:Copper mesh reception, voltage 12kv, reception distance 15cm, flow velocity 0.4ml/h;Normal temperature is placed in 50 DEG C of vacuum drying chambers after spinning, is dried to constant weight;
Step 6:By the amine-modified solution even application of DOPA in static spinning membrane surface, the thickness of spraying is 5-30nm, and Dried in 37 DEG C of drying boxes after 12h, rinsed 3 times with phosphate buffer (PBS), produce tissue renovation material.
Cell adhesion experiments:The HUVEC cells of culture are taken, are digested, cell count, with 5 × 103Cell/mL density is inoculated with On tissue renovation material made from embodiment 1 and blank control group poly-lactic acid material, per hole 1mL, after inoculation 0.5h, 1h, 2h, Rinsed with sterile PBS solution, as a result Microscopic observation and counting of taking a picture see the table below 1.It can be seen that after DOPA is amine-modified The cell quantity of the blank control group of the cell quantity that PLA tissue renovation material is adhered to significantly more than not by modification.
Table 1
Cell proliferation experiment:The HUVEC cells of culture are taken, are digested, cell count, with 5 × 103Cell/mL density is inoculated with On tissue renovation material made from embodiment 1 and blank control group poly-lactic acid material, per hole 1m L, liquid was changed every two days, is inoculated with After 5day, Cell counting Kit WST-8 detects the cytoactive of material surface, the results are shown in Table 2, it can be deduced that pass through dopamine The cytoactive of PLA tissue renovation material after modification is slightly above the cytoactive of blank assay group.
Table 2

Claims (5)

1. a kind of preparation method of DOPA structural modification PLA tissue renovation material, it is characterised in that comprise the following steps:
Step one:By 350mg Gelatins in 60mL water, heating water bath is molten to obtained gelatin is completely dissolved to 50 DEG C of stirrings Liquid;
Step 2:By gelatin solution and 150mg N- hydroxysuccinimides, 191mg 1- ethyls-(3- dimethylaminopropyls) Phosphinylidyne diimine and 103mg dopamines mixing, in electric heating constant temperature tank 40 DEG C stirring 48 hours after, solution is placed in bag filter In, it is put into the beaker for filling ultra-pure water, is placed in electric heating constant temperature tank and 2-3day is stirred under the conditions of 40 DEG C, and changed every 8h Ultra-pure water;
Step 3:The solution remained in bag filter is taken out, is placed in -20 DEG C of household freezers and freezes 8h, then is placed on freeze dryer dry 48h, obtains adhesiveness gelatin;
Step 4:Adhesiveness gelatin is made to the 3mg/ml aqueous solution, pH value of water solution is adjusted to 7 with HCl and NaOH, i.e., much The amine-modified solution of bar;
Step 5:PLA is dissolved into tetrafluoroethene, compound concentration is 10w/v% solution, under normal temperature after stirring 24h Spinning solution, static spinning membrane is obtained by electrostatic spinning, and normal temperature is placed in 50 DEG C of vacuum drying chambers, is dried to constant weight;
Step 6:By the amine-modified solution even application of DOPA in static spinning membrane surface, and dried in 37 DEG C of drying boxes after 12h, Rinsed 3 times with phosphate buffer (PBS), produce tissue renovation material.
2. a kind of preparation method of DOPA structural modification PLA tissue renovation material according to claim 1, its feature It is:Bag filter remaining molecules amount described in step 2 is 10000Da.
3. a kind of preparation method of DOPA structural modification PLA tissue renovation material according to claim 1, its feature It is:Ultrapure water consumption is to cover bag filter in described step two.
4. a kind of preparation method of DOPA structural modification PLA tissue renovation material according to claim 1, its feature It is, the spinning parameter of electrostatic spinning is in step 5:Copper mesh reception, voltage 12kv, reception are apart from 15cm, flow velocity 0.4ml/h.
5. a kind of preparation method of DOPA structural modification PLA tissue renovation material according to claim 1, its feature It is:The thickness sprayed in step 6 is 5-30nm.
CN201710330845.0A 2017-05-11 2017-05-11 A kind of preparation method of DOPA structural modification PLA tissue renovation material Pending CN107137764A (en)

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Publication number Priority date Publication date Assignee Title
CN108578767A (en) * 2018-02-01 2018-09-28 上海师范大学 Porous composite electrospun fibrous framework of a kind of orientation with bionic surface and its preparation method and application
CN110975009A (en) * 2019-12-17 2020-04-10 东南大学 Preparation method of electrostatic spinning fiber scaffold material
CN111407922A (en) * 2019-01-04 2020-07-14 上海交通大学 Black phosphorus composition, biological material containing black phosphorus composition, preparation method and application
CN112575576A (en) * 2021-01-15 2021-03-30 新疆师范大学 Preparation method of polydopamine/polylactic acid/nano-copper composite fiber membrane with photo-thermal/copper synergistic antibacterial function

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CN101507661A (en) * 2009-03-10 2009-08-19 广州迈普再生医学科技有限公司 Nano artificial dura mater with multi functional-layers and preparation method thereof
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108578767A (en) * 2018-02-01 2018-09-28 上海师范大学 Porous composite electrospun fibrous framework of a kind of orientation with bionic surface and its preparation method and application
CN108578767B (en) * 2018-02-01 2021-04-09 上海师范大学 Oriented porous composite electrospun fiber scaffold with bionic surface and preparation method and application thereof
CN111407922A (en) * 2019-01-04 2020-07-14 上海交通大学 Black phosphorus composition, biological material containing black phosphorus composition, preparation method and application
CN111407922B (en) * 2019-01-04 2021-04-02 上海交通大学 Black phosphorus composition, biological material containing black phosphorus composition, preparation method and application
CN110975009A (en) * 2019-12-17 2020-04-10 东南大学 Preparation method of electrostatic spinning fiber scaffold material
CN112575576A (en) * 2021-01-15 2021-03-30 新疆师范大学 Preparation method of polydopamine/polylactic acid/nano-copper composite fiber membrane with photo-thermal/copper synergistic antibacterial function
CN112575576B (en) * 2021-01-15 2023-11-24 新疆师范大学 Preparation method of polydopamine/polylactic acid/nano copper composite fiber membrane with photo-thermal/copper synergistic antibacterial function

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