CN109381732A - Electrostatic spinning dressing, preparation method and the application of growth factor-loaded micromolecular inhibitor - Google Patents
Electrostatic spinning dressing, preparation method and the application of growth factor-loaded micromolecular inhibitor Download PDFInfo
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- CN109381732A CN109381732A CN201710657821.6A CN201710657821A CN109381732A CN 109381732 A CN109381732 A CN 109381732A CN 201710657821 A CN201710657821 A CN 201710657821A CN 109381732 A CN109381732 A CN 109381732A
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- growth factor
- electrostatic spinning
- inhibitor
- dressing
- spinning
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- Materials For Medical Uses (AREA)
Abstract
本发明提供了一种负载生长因子小分子抑制剂的静电纺丝敷料及其制备方法和应用。本发明的静电纺丝方法制备的纤维膜具有稳定的理化性能及高的孔隙率，能够隔绝污染物并柔软透气；将高分子聚合物与天然高分子材料结合制备的纤维膜具有更强的机械性能，而天然高分子能够增强纺丝纤维膜的细胞相容性，使细胞更容易在纤维膜上生长，促进伤口愈合；TGF‑β1抑制剂信号通路明了，针对性更强，能够有效抑制瘢痕的形成；纤维膜具有较好的浸润性，能够与不同形状的伤口完美贴合，选用可降解材料制备，减少了更换敷料带来的二次伤害；制备方法简单，使用便捷，具有巨大的临床应用前景。
The invention provides an electrospinning dressing loaded with a growth factor small molecule inhibitor and a preparation method and application thereof. The fiber membrane prepared by the electrospinning method of the present invention has stable physical and chemical properties and high porosity, can isolate pollutants and is soft and breathable; the fiber membrane prepared by combining high molecular polymers with natural high molecular materials has stronger mechanical properties Natural polymers can enhance the cytocompatibility of spun fiber membranes, make it easier for cells to grow on the fiber membranes, and promote wound healing; TGF-β1 inhibitors have a clear signaling pathway and are more targeted, which can effectively inhibit scarring. The fibrous membrane has good infiltration and can be perfectly fitted with wounds of different shapes. It is prepared by using degradable materials, which reduces the secondary injury caused by changing dressings. The preparation method is simple, easy to use, and has huge clinical benefits. application prospects.
Description
Technical field
The invention belongs to medical bio fields, and in particular to a kind of electrostatic spinning of growth factor-loaded micromolecular inhibitor
Dressing, and its preparation method and application.
Background technique
Skin is the maximum organ of human body, has barrier protection, adjusts body temperature, secretion and excretion, absorption and metabolism, is immune
Etc. physiological functions.Wound healing process is divided into the period of three independences and overlapping: (1) inflammatory phase: occurs at 24-48 hours,
Its sign is local temperature increase, rubescent, swelling, and the function in this stage is to remove dead bacterium and cell, promotes healing
Process.(2) proliferative phase: 48 hours about after wound, this phase characterized by fibroblastic activity, is mainly shown as epithelium again
Change and granulation tissue is formed.(3) remold the phase: about 21 days after wound start, interim at this, and fibroblast number is reduced, and collagen egg
White to continue to adhere, granulation tissue is converted to cicatricial tissue, and the scar of excess fibrosis is difficult to be absorbed by organisms, and gives post-traumatic function
It can restore and rebuild to bring very big obstacle.Hyperplastic scar is a kind of skin disease as caused by skin corium disorder, is often sent out
After being born in deep burn or rats after severe scald burn, and the quality of life of patient by this disease as be decreased obviously.In prosperity
Country, scar caused by thering are 4,000,000 patients to lead to hyperplastic scar or burning because of scald every year, and the morbidity of developing country
Rate is more surprising.The optimal method for repairing hyperplastic scar is that necessary intervening measure is taken in Process of Forming Scar.Such as
The present, the method for treating and preventing scar are specifically included that in lesion locally injecting corticosteroid, silica gel patch, pressure therapy, laser
Treatment, cold therapy, radiotherapy and surgical operation therapy.But due to high recurrence rate, therapeutic effect it is limited and cause it is a variety of simultaneously
Disease is sent out, cannot achieve and effectively eradicate scar, cause financial burden and at heart shade to patient, influence appearance.But also it stays
Lower sequelae.Nowadays, the method for treating and preventing scar is specifically included that in lesion locally injecting corticosteroid, silica gel patch, pressure
Power treatment, laser therapy, cold therapy, radiotherapy and surgical operation therapy.But due to high recurrence rate, therapeutic effect it is limited and
Cause multiple complications, cannot achieve and effectively eradicate scar, cause financial burden and at heart shade to patient, influences outer
It sees.But also leave sequelae.Therefore, exploring can prevent the fresh wound dressing of scar from having great importance.
With wound dressing progress of research, ideal functionality medical wound dressing should include (1) dressing can be effective
The entire surface of a wound is covered, the position including some more difficult coverings is stopped blooding rapidly；(2) there is certain elasticity, can adapt to body
Movement；(3) diffusate of wound is absorbed, to guarantee the ambient humidity of wound；(4) pain during change of dressing is reduced；(5)
Good biocompatibility；(6) wound infection is prevented.Electrostatic spinning technique as it is a kind of prepare micro/nano-fibre have efficacious prescriptions
There is method other sizes material to be difficult to the excellent attribute surmounted, and such as: big specific surface area, excellent physical and chemical performance are wide
It is general to be applied to biomedicine, the fields such as wound dressing and drug delivery.Domestic and foreign scholars apply in the wound for the treatment of hyperplastic scar
Material aspect has done some explorations, still, has the following problems: complicated component, and the influence between Multiple components is unclear；Preparation process
It is cumbersome；It needs to depend on other dressing, cannot achieve slow release, be not suitable for the use of long-term treatment.
Summary of the invention
Therefore, the purpose of the present invention is to overcome the defects in the prior art, provides a kind of growth factor-loaded small molecule
The electrostatic spinning dressing of inhibitor, and its preparation method and application.
Before illustrating the content of present invention, it is as follows to define term used herein:
Term " high molecular polymer " refers to: repeating to connect by covalent bond by many identical, simple structural units
Made of high molecular weight (usually up to 104~106) compound.
Term " natural polymer " refers to: in the composition of nature animals and plants (including humans), by repetitive unit
The line style long-chain connected into is the high-molecular weight compounds of basic structure.
Term " growth factor micromolecular inhibitor " refers to: molecular weight less than 5000, for block or reduce growth because
The activity of subclass substance or the substance of reaction speed.
Term " PEG " refers to: polyethylene glycol.
Term " PLA " refers to: polylactic acid.
Term " PVA " refers to: polyvinyl alcohol.
Term " PCL " refers to: polycaprolactone.
Term " PLGA " refers to: poly lactide-glycolide acid.
Term " 1 inhibitor of TGF-β " refers to: conversion growth factor-beta inhibitor (TGF-β 1, SB-525334,6- [2-
tert-butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quin oxaline)。
To achieve the above object, the first aspect of the present invention provides a kind of the quiet of growth factor-loaded micromolecular inhibitor
Electrospun dressing, the dressing include:
It is 10 by line style long-chain natural high molecular substance and weight average molecular weight4~106High molecular polymer made of electrostatic
Spinning film；With
The growth factor micromolecular inhibitor loaded.
The electrostatic spinning dressing of growth factor-loaded micromolecular inhibitor according to a first aspect of the present invention, the macromolecule
Polymer is selected from one or more of: polyethylene glycol, polylactic acid, polyvinyl alcohol, polycaprolactone, poly lactic-co-glycolic acid are total
Polymers, polyacrylonitrile, polystyrene and Kynoar；
The natural high molecular substance is selected from one or more of: fibroin, chitosan, cellulose, gelatin, collagen
And hyaluronic acid；
The growth factor micromolecular inhibitor is selected from one or more of: 1 inhibitor of TGF-β, blood vessel endothelial factor
Inhibitor, fibroblast growth factor inhibitor, ginseng sapoglycoside Rg 3 and bone morphogenetic protein inhibitor.
The second aspect of the present invention provides the electrostatic spinning dressing that micromolecular inhibitor is loaded described in first aspect
Preparation method the described method comprises the following steps:
(1) high molecular polymer, natural polymer and micromolecular inhibitor are added in solvent, with magnetic stirring apparatus room temperature
Stirring, makes high molecular polymer, natural polymer and the growth factor micromolecular inhibitor dissolve and be uniformly mixed, is configured to
Electrostatic spinning precursor liquid；
(2) the electrostatic spinning precursor liquid sucking configured in step (1) is fixed in the syringe promoted on pump
Electrostatic spinning is carried out, vacuum drying can be obtained the electrostatic spinning dressing for loading the growth factor micromolecular inhibitor.
Preparation method according to a second aspect of the present invention, wherein in the step (1), the solvent is selected from following one kind
It is or a variety of: hexafluoroisopropanol, ethyl alcohol, acetone, chloroform, tetrahydrofuran, formic acid and N, N-dimethylformamide.
Preferably, in the step (1), first high molecular polymer and natural polymer are added in solvent, magnetic agitation
Device stirring at normal temperature is dissolved and is uniformly mixed, and adds the growth factor micromolecular inhibitor, and magnetic stirring apparatus stirring at normal temperature is molten
It solves and is uniformly mixed, spinning precursor liquid is made.
Preferably, in the step (1), the electrostatic spinning precursor liquid mass fraction is 5~20 mass %；More preferably
Ground, the electrostatic spinning precursor liquid are the mixture of 10 mass %PCL and gelatin.
Preferably, the concentration of the growth factor micromolecular inhibitor be 0.1~10 it is micro- rub/liter, preferably 1~10 is micro-
Rub/liter, more preferably 4~6 it is micro- rub/liter, most preferably 5 it is micro- rub/liter.
Preferably, during electrostatic spinning described in the step (2): 0.8~1.5 milliliter of rate of propulsion pump propulsion/small
When and keep spinning solution flow stablize；Spinning nozzle is the plain head that diameter is 0.2~0.6 millimeter, with high-voltage DC power supply 10
~20 kilovolts of anodes are connected；Spinning nozzle is with collecting 6~10 centimetres of distance of interpolar；
It is highly preferred that the propulsion pump promotes 1.2 mls/hour of rate；The plain that the spinning nozzle is 0.4 millimeter
Head；The high voltage power supply is 17 kilovolts；The collection spacing is 8 centimetres.
The third aspect of the present invention provides the Static Spinning of growth factor-loaded micromolecular inhibitor described in first aspect
Silk dressing or the electrostatic spinning dressing of the growth factor-loaded micromolecular inhibitor prepared according to method described in second aspect
Application in manufacture medical instrument or medical supplies.
Preferably, the medical instrument or medical supplies are used for clinical treatment of wounds, beauty, treatment burn, scald, bedsore
Infection.
It is an object of the invention to propose that a kind of 1 inhibitor of conversion growth factor-β of secreting type type i collagen containing blocking is small
The preparation method and application of electrostatic spinning dressing and the electrostatic spinning containing the small molecule dressing of molecule.In conjunction with polyphosphazene polymer
The electrostatic spinning dressing for closing object and natural polymer shows excellent mechanical property, thermal stability and outstanding bio-safety
Property.The medicament-carrying nano-fiber membrane shows to promote wound healing in animal experiments and inhibits the ability of cicatrization.
In order to realize the application for the functional medical wound dressing thought, present invention design provides that a kind of cost is low, curative effect
Good, the simple medical bio suppression scar dressing of preparation method preparation method.The material of electrospinning includes: 1, high molecular polymerization species:
Polyethylene glycol (PEG), polylactic acid (PLA), polyvinyl alcohol (PVA), polycaprolactone (PCL), poly lactide-glycolide acid
(PLGA) etc.；2, natural polymer subclass: fibroin, chitosan, cellulose, gelatin, collagen etc..With the height of good biocompatibility
Molecularly Imprinted Polymer and natural polymer carry out electrostatic spinning, by the biology of the mechanical property of high molecular polymer and natural polymer
Performance perfect combination.Electrostatic spinning prepares composite cellulosic membrane with porous microstructure, structure similar with extracellular matrix
The adherency and migration for being conducive to cell, can promote the healing of wound as the pharmaceutical carrier of skin repair dressing.Transforming growth
The factor-β inhibits (TGF-β 1, SB-525334,6- [2-tert-butyl-5- (6-methyl-pyridin-2-yl) -1H-
Imidazol-4-yl]-quinoxaline) it is a kind of small molecule compound, pass through the intracellular second messenger of phosphorylation and downstream
Transcription modulator, for inhibiting secreting type type i collagen, to prevent cicatrization.The schematic diagram that the present invention designs such as Fig. 1 institute
Show.Inhibitor is added in spinning precursor liquid, the wound dressing of the inhibition scar of preparation load small molecule.In use,
With the degradation of gelatin, micromolecular inhibitor is gradually released from electrospun fiber membrane, realizes the effect of sustained release.Further lead to
The animal model for crossing rabbit ear hyperplastic scar demonstrates the feasibility of this functional skin dressing.
In order to realize the application for the functional medical wound dressing thought, present invention design provides that a kind of cost is low, curative effect
Good, the simple medical bio suppression scar dressing of preparation method preparation method.In conjunction with the quiet of high molecular polymer and natural polymer
Electrospun dressing shows excellent mechanical property, thermal stability and outstanding biological safety.Growth factor receptor inhibitors are small
Molecule is added in spinning precursor liquid, blocks secreting type type i collagen, the medicament-carried nano by 1 inhibitor of conversion growth factor-β
Tunica fibrosa shows to promote wound healing in animal experiments and inhibits the ability of cicatrization.
To achieve the goal, the invention adopts the following technical scheme:
The electrostatic spinning load small molecule provided according to the present invention is used to inhibit the preparation method of scar wound dressing and answers
With, wherein the electrospinning precursor liquid selects high molecular polymer PCL and PLGA；Natural polymer selects gelatin and collagen.It is preferred that
Ground, 5~20 mass % (i.e. mass percent) of precursor liquid mass fraction.More preferably electrospinning precursor liquid selects 10 mass %
The mixture of PCL and gelatin.
The suppression scar electrostatic spinning dressing of the small molecule containing growth factor receptor inhibitors provided according to the present invention, wherein the tool
There is 1 inhibitor of conversion growth factor-β of suppression scar performance.Preferably, the concentration of 1 inhibitor of conversion growth factor-β be 1~
10 it is micro- rub/liter.More preferably 5 it is micro- rub/liter.
The present invention also provides the preparation methods that above-mentioned electrostatic spinning load small molecule is used to inhibit scar wound dressing, push away
0.8~1.5 ml/hour of rate is promoted into pump and spinning solution flow is kept to stablize；Spinning nozzle is that diameter is 0.2~0.6 milli
The plain head of rice, is connected with 10~20 kilovolts of anodes of high-voltage DC power supply；Spinning nozzle is with collecting 6~10 lis of distance of interpolar
Rice.Preferably, 1.2 mls/hour of rate are promoted；0.4 millimeter of spinning nozzle of plain head；17 kilovolts of high voltage power supply；Between collection
Away from 8 centimetres.
Inhibition scar wound dressing good hydrophilic property prepared by the present invention, the water absorption of tunica fibrosa can be up to 600%；It selects
Biodegradable material, composite nano-fiber membrane shows that mass loss is by the slow linear water of gelatin in fiber in the last fortnight
Solution causes；Although gelatin is easily decomposes, spinning fibre film can't decompose before 300 DEG C, this is sufficient for as life
Object dressing is used for the use condition of high-temperature sterilization, has good thermal stability；Electrospinning fibre is tested using tensile testing machine
The mechanical performance of film, the tensile strength of tunica fibrosa be about 2 megapascal, this has met depends on as regeneration materials for support
It is required that.
In order to realize the application of ideal functional medical wound dressing, the cost that present invention design provides one kind is low, treats
Imitate, preparation method is simple, the preparation method of the medical bio of good biocompatibility suppression scar dressing, the dressing was using
Cheng Zhong, with the degradation of gelatin, micromolecular inhibitor is gradually released from electrospun fiber membrane, realizes the effect of sustained release, energy
The formation that enough can effectively inhibit scar can be used for clinical treatment of wounds, beauty, the various wounds such as treatment burn, scald, bedsore infection
Wound, is a kind of superfine medical dressing.
The present invention mainly proposes a kind of 1 inhibitor small molecule of conversion growth factor-β of secreting type type i collagen containing blocking
The preparation method and application of electrostatic spinning dressing and the electrostatic spinning containing small molecule dressing.Electrospinning process preparation
Tunica fibrosa has stable physicochemical property and high porosity, can completely cut off pollutant and flexible, breathable.1 inhibitor of TGF-β letter
Number access is illustrated, and specific aim is stronger, can effectively inhibit the formation of scar.
The present invention mainly proposes a kind of 1 inhibitor small molecule of conversion growth factor-β of secreting type type i collagen containing blocking
The preparation method and application of electrostatic spinning dressing and the electrostatic spinning containing small molecule dressing.By high molecular polymer and day
Right high molecular material combines the tunica fibrosa of preparation to have stronger mechanical performance, and natural polymer can enhance spinning fibre film
Cell compatibility, make cell be easier grown on tunica fibrosa, promote wound healing.Preparation method is simple, easy to use, tool
There is huge potential applicability in clinical practice.
The present invention mainly proposes a kind of 1 inhibitor small molecule of conversion growth factor-β of secreting type type i collagen containing blocking
The preparation method and application of electrostatic spinning dressing and the electrostatic spinning containing small molecule dressing.Tunica fibrosa has preferable leaching
Lubricant nature can be bonded with wound perfection of different shapes, select degradation material preparation, and it is secondary to reduce replacement dressing bring
Injury, with the degradation of gelatin, micromolecular inhibitor is gradually released from electrospun fiber membrane, realizes the effect of sustained release.
1 inhibitor signal path of TGF-β is illustrated, and specific aim is stronger, can effectively inhibit the formation of scar.
The electrostatic spinning dressing of load micromolecular inhibitor of the invention can have but be not limited to it is following the utility model has the advantages that
1, the tunica fibrosa of electrospinning process preparation has stable physicochemical property and high porosity, can completely cut off pollution
Object and flexible, breathable；
2, the tunica fibrosa for preparing high molecular polymer in conjunction with natural macromolecular material has stronger mechanical performance, and
Natural polymer can enhance the cell compatibility of spinning fibre film, make cell be easier to grow on tunica fibrosa, promote wound
Healing；
3,1 inhibitor signal path of TGF-β is illustrated, and specific aim is stronger, can effectively inhibit the formation of scar；
4, tunica fibrosa has preferable wellability, can be bonded with wound perfection of different shapes, selects degradation material
Preparation reduces replacement dressing bring secondary injury；
5, preparation method is simple, easy to use, has huge potential applicability in clinical practice.
Detailed description of the invention
Hereinafter, carrying out the embodiment that the present invention will be described in detail in conjunction with attached drawing, in which:
The schematic diagram for the electrostatic spinning preparation load small molecule wound dressing that the present invention that Fig. 1 shows designs.
Fig. 2 shows polymer nanofiber scanning electron microscopic picture prepared by embodiment 1.PCL and gelatin are embodiments 1
Spinning material, PGT are the spinning fibre film of 1 inhibitor of embodiment 1PCL/ gelatin+TGF β preparation, and PG is the blank pair of embodiment 1
According to spinning fibre film, material is PCL/ gelatin.
Fig. 3 shows the polymer nanofibre film performance characterization of the preparation of embodiment 1.PCL and gelatin are the spinnings of embodiment 1
Wire material, PGT are the spinning fibre film of 1 inhibitor of embodiment 1PCL/ gelatin+TGF β preparation, and PG is the blank control of embodiment 1
Spinning fibre film, material are PCL/ gelatin.
Fig. 4 shows the polymer nanofibre film results of animal of the preparation of embodiment 1.
Fig. 5 shows the polymer nanofibre film performance characterization of the preparation of embodiment 2.
Fig. 6 shows the polymer nanofibre film performance characterization of the preparation of embodiment 3.
Fig. 7 shows the polymer nanofibre film performance characterization of the preparation of embodiment 4.
Specific embodiment
Present invention will be further explained by specific examples below, it should be understood, however, that, these embodiments are only
It is used, is but should not be understood as present invention is limited in any form for specifically describing in more detail.
This part carries out general description to the material and test method that arrive used in present invention test.Although being
It realizes many materials used in the object of the invention and operating method is it is known in the art that still the present invention still uses up herein
It may detailed description.It will be apparent to those skilled in the art that within a context, if not specified, material therefor of the present invention and behaviour
It is well known in the art as method.
Reagent and instrument used in the following embodiment are as follows:
Reagent:
Polycaprolactone is purchased from Sigma, and gelatin is purchased from Sigma, and poly lactide-glycolide acid is purchased from Sigma, glue
Original, is purchased from Sigma, and hexafluoroisopropanol is purchased from Sigma；1 inhibitor of TGF-β is purchased from Selleck Chemicals.
Instrument:
Magnetic stirring apparatus is purchased from Changzhou Guohua Electric Appliance Co., Ltd., model HJ-4A.
Scanning electron microscope is purchased from Hitachi, Japan, model Hitachi S4800+EDS.
Static Contact angle tester is purchased from Germany KRUSS, model DSA100.
Thermogravimetric analyzer is purchased from PerkinElmer Instrument Ltd., model TGA/DSC 1.
Tensile testing machine is purchased from Instron Corporation, the U.S., model Instron5567.
High-voltage DC power supply is purchased from Tianjin Dongwen High-Voltage Power Supply Co., Ltd., model DW-P403-1ACF7.
Embodiment 1
The device figure that the present invention designs is as shown in Figure 1.Illustrate spinning process below by specific embodiment, step is such as
Under:
(1) in conical flask, by 0.75 gram of polycaprolactone (PCL, molecular weight 80000, Sigma), 0.25 gram of gelatin
(gelatin, A type powder, come from porcine skin, Sigma) and 5 milliliter 5 it is micro- rub/liter 1 inhibitor (TGF-β of TGF-β
Inhibitor, 6- [2-tert-butyl-5- (6-methyl-pyridin-2-yl) -1H-imidazol-4-yl] -
Quinoxalin, SB525334, Selleck Chemicals), 10 milliliters of hexafluoroisopropanol (1,1,1,2,2,2- is added
Hexafluoro-2-propanol, HFIP, Sigma) in, stirred 2 hours under magnetic stirring apparatus room temperature, make PCL, gelatin and
1 inhibitor of TGF-β is dissolved and is uniformly mixed in HFIP, is configured to transparent spinning forerunner liquor.
(2) sucking of configured electrostatic spinning precursor liquid is fixed in the syringe promoted on pump, pump is promoted to promote speed
1.2 mls/hour of rate simultaneously keeps spinning solution flow to stablize；Spinning nozzle is the plain head that diameter is 0.4 millimeter, with high voltage direct current
17 kilovolts of anodes of power supply are connected；Spinning nozzle is with collecting 8 centimetres of distance of interpolar.After 2 hours, load inhibitor can be obtained
PCL/ gelatin composite cellulosic membrane (PGT).The nano fibrous membrane of acquisition is 24 hours dry in vacuum desiccator, make not wave
Removal of sending out organic solvent complete.Observation result is as shown in Figure 2 under a scanning electron microscope.
(3) preparation method of the composite cellulosic membrane (PG) of blank control PCL/ gelatin and the PCL/ gelatin of load inhibitor
The method of composite cellulosic membrane (PGT) is identical, and difference is added without 1 inhibitor of TGF-β during being only that preparation spinning precursor liquid.
(4) gelatin of electrospinning, the moistened surface of PCL, PG and PGT nano fibrous membrane are assessed by Static Contact angle tester
Property, as a result as shown in Figure 3A, in addition to the electrospun fiber membrane of PCL, other are hydrophilic, and the contact angle of PCL is 120 degree.
The water absorbing capacity of film is analyzed by the mass change of test electrospinning composite nanofiber membrane water suction front and back, as a result as shown in Figure 3B
The water absorption of electrospun fiber membrane can be up to 600%；Compare the mass loss table of the spinning dry film after impregnating different time drying
The degradation property of electrospun fiber membrane is levied, as a result as shown in Figure 3 C, composite nano-fiber membrane shows that mass loss is in the last fortnight
Caused by slowly linearly being hydrolyzed as gelatin in fiber.The thermal stability of electrospun fiber membrane is tested by thermogravimetric analyzer.As a result
As shown in Figure 3D, although gelatin is easily decomposes, spinning fibre film can't decompose before 300 DEG C, this is sufficient for making
The use condition of high-temperature sterilization is used for for biological dressing.The mechanical performance of electrospun fiber membrane is tested using tensile testing machine.Knot
As shown in FIGURE 3 E, the tensile strength of tunica fibrosa is about 2 megapascal to fruit, this has met depends on as regeneration materials for support
It is required that.
(5) anti-cicatrization effect of the tunica fibrosa on the skin holostrome damage wound in rabbit ear scar model.Each
The ventral surface of ear constructs the circular wound that four diameters are 1.0 centimetres, and the position of rabbit ears is randomly divided into four groups of (n
=3) 1 (blank control group), is organized；2 (hospital gauze groups) of group；3 (blank spinning fibre film groups) of group；Group 4 (carries medicine spinning fibre film
Group).As a result as shown in Figure 4 A, after hand month after operation, it is other that the size of the wound of electrospun fiber membrane treatment is significantly less than other groups
Wound size, 4 groups of wounds reduce 75 ± 5%, 94 ± 2%, 100 ± 3% and 100 ± 1% respectively.After operation after 2 months, blank
There is irregular protrusion at the center of wound in control, gauze and blank spinning fibre film group, carry medicine group skin and restore completely
And not raised phenomenon.By carrying out Western blotting measurement come the collagen of quantitative wound tissue, as a result such as Fig. 4 B, art
1 month afterwards, PGT group Collagen type I quantity was lower than other groups.Postoperative 2 months, PGT group showed the horizontal significant reduction of type i collagen, showed
Show that inhibitor is the main reason for reducing type i collagen deposition.
Embodiment 2
Steps are as follows:
(1) in conical flask, by 1.2 grams of poly lactide-glycolide acids (PLGA, 50/50,12000, Sigma),
0.3 gram of collagen (I type, Sigma) and 5 milliliter 5 it is micro- rub/liter 1 inhibitor of TGF-β, be added in 10 milliliters of hexafluoroisopropanol,
It is stirred 2 hours under magnetic stirring apparatus room temperature, so that PLGA and collagen is dissolved and is uniformly mixed in HFIP, be configured to transparent spinning
Silk precursor liquid.
(2) spinning process is same as Example 1.
(3) composite cellulosic membrane performance characterization is same as Example 1, as shown in Figure 5.
Embodiment 3
Steps are as follows:
(1) in conical flask, by 1.0 grams of PLGA, 0.5 gram of gelatin and 5 milliliter 5 it is micro- rub/liter 1 inhibitor of TGF-β,
It is added in 10 milliliters of hexafluoroisopropanol, is stirred 2 hours under magnetic stirring apparatus room temperature, dissolve PLGA and gelatin in HFIP
And be uniformly mixed, it is configured to transparent spinning precursor liquid.
(2) spinning process is same as Example 1.
(3) composite cellulosic membrane performance characterization is same as Example 1, as shown in Figure 6.
Embodiment 4
Steps are as follows:
(1) in conical flask, by 0.8 gram of PCL, 0.2 gram of collagen and 5 milliliter 5 it is micro- rub/liter 1 inhibitor of TGF-β,
It is added in 10 milliliters of hexafluoroisopropanol, is stirred 2 hours under magnetic stirring apparatus room temperature, dissolve PCL and collagen in HFIP
And be uniformly mixed, it is configured to transparent spinning precursor liquid.
(2) spinning process is same as Example 1.
(3) composite cellulosic membrane performance characterization is same as Example 1, as shown in Figure 7.
Although present invention has been a degree of descriptions, it will be apparent that, do not departing from the spirit and scope of the present invention
Under the conditions of, the appropriate variation of each condition can be carried out.It is appreciated that the present invention is not limited to the embodiments, and it is attributed to right
It is required that range comprising the equivalent replacement of each factor.
Claims (10)
1. a kind of electrostatic spinning dressing of growth factor-loaded micromolecular inhibitor, which is characterized in that the dressing includes:
It is 10 by line style long-chain natural high molecular substance and weight average molecular weight4~106High molecular polymer made of electrostatic spinning
Film；With
The growth factor micromolecular inhibitor loaded.
2. the electrostatic spinning dressing of growth factor-loaded micromolecular inhibitor according to claim 1, which is characterized in that institute
It states high molecular polymer and is selected from one or more of: polyethylene glycol, polylactic acid, polyvinyl alcohol, polycaprolactone, polylactic acid-glycolic
Acetic acid copolymer, polyacrylonitrile, polystyrene and Kynoar；
The natural high molecular substance be selected from one or more of: fibroin, chitosan, cellulose, gelatin, collagen and thoroughly
Bright matter acid；
The growth factor micromolecular inhibitor is selected from one or more of: 1 inhibitor of TGF-β, blood vessel endothelial factor inhibit
Agent, fibroblast growth factor inhibitor, ginseng sapoglycoside Rg 3 and bone morphogenetic protein inhibitor.
3. the preparation method of the electrostatic spinning dressing of growth factor-loaded micromolecular inhibitor according to claim 1 or 2,
It is characterized in that, the described method comprises the following steps:
(1) high molecular polymer, natural polymer and growth factor micromolecular inhibitor are added in solvent, use magnetic stirring apparatus
Stirring at normal temperature makes high molecular polymer, natural polymer and the growth factor micromolecular inhibitor dissolve and be uniformly mixed, matches
Electrostatic spinning precursor liquid is made；
(2) the electrostatic spinning precursor liquid sucking configured in step (1) is fixed in the syringe promoted on pump and is carried out
Electrostatic spinning, vacuum drying, can be obtained the electrostatic spinning dressing for loading the growth factor micromolecular inhibitor.
4. according to the method described in claim 3, it is characterized in that, in the step (1), the solvent be selected from it is following a kind of or
It is a variety of: hexafluoroisopropanol, ethyl alcohol, acetone, chloroform, tetrahydrofuran, formic acid and N, N-dimethylformamide.
5. the method according to claim 3 or 4, which is characterized in that in the step (1), first by high molecular polymer and
Natural polymer is added in solvent, and magnetic stirring apparatus stirring at normal temperature is dissolved and is uniformly mixed, and adds small point of the growth factor
Sub- inhibitor, magnetic stirring apparatus stirring at normal temperature are dissolved and are uniformly mixed, and spinning precursor liquid is made.
6. method according to any one of claim 3 to 5, which is characterized in that in the step (1), the Static Spinning
Silk precursor liquid mass fraction is 5~20 mass %；Preferably, the electrostatic spinning precursor liquid is 10 mass %PCL and gelatin
Mixture.
7. method according to any one of claim 3 to 6, which is characterized in that the growth factor micromolecular inhibitor
Concentration be 0.1~10 it is micro- rub/liter, preferably 1~10 it is micro- rub/liter, more preferably 4~6 it is micro- rub/liter, most preferably 5 it is micro- rub/
It rises.
8. the method according to any one of claim 3 to 7, which is characterized in that electrostatic spinning described in the step (2)
In the process: promoting pump to promote 0.8~1.5 ml/hour of rate and spinning solution flow is kept to stablize；Spinning nozzle is that diameter is
0.2~0.6 millimeter of plain head is connected with 10~20 kilovolts of anodes of high-voltage DC power supply；Spinning nozzle with collect interpolar away from
From 6~10 centimetres；
Preferably, the propulsion pump promotes 1.2 mls/hour of rate；The plain head that the spinning nozzle is 0.4 millimeter；It is described
High voltage power supply is 17 kilovolts；The collection spacing is 8 centimetres.
9. the electrostatic spinning dressing of growth factor-loaded micromolecular inhibitor of any of claims 1 or 2 or according to claim 3
The electrostatic spinning dressing of growth factor-loaded micromolecular inhibitor for preparing is in manufacture medical treatment to method described in any one of 8
Application in instrument or medical supplies.
10. application according to claim 9, which is characterized in that the medical instrument or medical supplies are used for clinical wound
Processing, beauty, treatment burn, scald, bedsore infection.
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| CN114306712A (en) * | 2021-12-30 | 2022-04-12 | 东华大学 | A kind of scald dressing for reducing swelling and pain relief and its preparation and application |
| CN115364270A (en) * | 2022-04-11 | 2022-11-22 | 北京化工大学 | Preparation method of antibacterial and antioxidant fiber film dressing containing traditional Chinese medicines |
| CN119158061A (en) * | 2024-11-21 | 2024-12-20 | 修原(辽宁)生物有限公司 | Biodegradable tissue repair functional dressing and preparation method thereof |
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Application publication date: 20190226 |