A kind of tissue repair fibrous membrane and manufacture method thereof and applicationTechnical field
The present invention relates to tissue repair fibrous membrane and manufacture method thereof and application, andTissue repair goods.
Background technology
Histoorgan reparation is a worldwide difficult medical problem.In modern surgery operation,Often need to repair, tissue and organ such as hernia repair, female pelvic floor functionObstacle disease reparation, hard brain/spinal meninges defect repair, nerve trachea defect repair, bloodThe reparation of pipe, ligament repair, bone defect healing etc..Due to human tissue structure andThe particularity of function, preferable tissue repair fibrous membrane need to possess following performance: 1.Certain intensity, it is possible to opposing mechanical stress, is not fully developed it at health tissuesFront wanting can bear Intraabdominal pressure；2. it is easy to cell adhesion, creeps and grow,Realize tissue regeneration；3. prevent from antibacterial from hiding to grow, it is to avoid because using artificial bio-membrane to closeBecome material and the infection that causes；4. good dimensionally stable can be kept after implanting human bodyProperty, i.e. can not shrink and deform；5. Stability Analysis of Structures, it is simple to be cut into needsShape and do not decoherence, it is simple to tissue apposition；The most soft, it is simple to molding, increasingThe operability adding operation, the sense of discomfort reducing patient, the effect of raising operation；⑦Good biocompatibility, can guide tissue growth, reaches preferable reparation.
Existing tissue repair fibrous membrane, often there are the following problems:
1) establishment mesh sheet is product most widely used in current tissue repair fibrous membrane,But such product surface is coarse, quality is harder, poor biocompatibility, be easily generated foreign bodySense and pain, cause the complication such as common erosion and infection；And such material causesImmunological rejection relatively strong, there is more postoperative complication；It is with internal organs, deviceWhen official directly contacts, easily cause damage, can cause more serious adhesion, cause seriousForeign body and immunoreation, need second operation to take out, bring misery to patient, veryTo threat to life.
2) the electrospinning film of at present research, common occur cell to be difficult to inside it growing into orGrow into slow deficiency.
As can be seen here, the tissue repair fibrous membrane that existing braiding, electrospinning are formedPerformance not ideal enough.
Summary of the invention
The problem that invention is to be solved
The present invention makes in view of above-mentioned problem of the prior art.Purpose is to carryFor a kind of tissue repair fibrous membrane, it has good mechanical strength, it is possible to notRepair premise completely for enough mechanical support, and beneficially cell adhesion and propagation,Guiding cell breaks up, and is conducive to the tight suture between tissue, reduces tissue repair and usesGoods shrinkage, cause infect and with the generation of the situation such as internal organs adhesion, improve patientComfort, and quickly repair, reduce the misery of patient.
For solving the scheme of problem
Present inventor it has been investigated that, specific by making tissue repair fibrous membrane haveLoft, it is possible to achieve above-mentioned purpose, thus complete the present invention.
Thus, the present invention provides a kind of tissue repair fibrous membrane, described fibrous membrane byThe cellosilk of a diameter of 10nm ~ 100 μm is interwoven, and has vesicular texture, and it is fluffyLooseness is 200 ~ 2000cm3/g。
The tissue repair fibrous membrane of the present invention can be according to the different cellosilk materials usedMaterial, selects suitable manufacture method to prepare.
A kind of preferably manufacture method of tissue repair fibrous membrane of the present invention includes as followsStep:
(1) by cellosilk materials different for two kinds of dissolution properties, it is dissolved in corresponding respectivelyIn solvent, obtain the cellosilk material solution of both of which one；
(2) the both of which one cellosilk material solution difference that will obtain in step (1)Loading in different electrostatic spinning syringes, the corresponding nozzle needle of two kinds of cellosilk materials existsOn high-tension electricity source plate evenly distributed, carry out electrostatic spinning, obtain two kinds of dissolution properties notThe fibrous membrane of the same crisscross intersection of cellosilk；
(3) according to the dissolution properties of cellosilk material, with suitable solvent by step (2)A kind of cellosilk in the fibrous membrane of middle manufacture dissolves, and another then keeps constant,Obtain described tissue repair fibrous membrane.
The another kind of preferable production process of tissue repair fibrous membrane of the present invention, including such asLower step:
(1) cellosilk material is dissolved in solvent, obtains homogeneous cellosilk material moltenLiquid；
(2) the homogeneous cellosilk material solution obtained in step (1) is loaded electrostaticIn spinning syringe, carry out electrostatic spinning and obtain fiber, and fiber is received as membranaceousStructure, obtains fibrous membrane；
(3) by the fibrous membrane for preparing in step (2) after solvent supersonic is swellingState under in predetermined temperature, carry out pre-freeze, then carry out vacuum lyophilization,To tissue repair fibrous membrane.
Another preferable production process of tissue repair fibrous membrane of the present invention, including such asLower step:
(1) cellosilk material is dissolved in solvent, obtains homogeneous cellosilk material moltenLiquid；
(2) the homogeneous cellosilk material solution obtained in step (1) is loaded electrostaticIn spinning syringe, carry out electrostatic spinning and obtain fiber, and fiber is received as membranaceousStructure, obtains fibrous membrane；
(3) by the fibrous membrane of preparation in step (2) along the transverse axis of fibrous membrane or the longitudinal axisOne of direction stretching, stop stretching after make fibrous membrane shape under this extended state；Then by fibrous membrane along the direction stretching vertical with above-mentioned draw direction of fibrous membrane, stopOnly make fibrous membrane shape under this extended state after stretching, obtain tissue repair fineDimension film.
The present invention also provides for described tissue repair fibrous membrane in the tissue repair system of manufactureApplication in product.
The present invention further provides and repaiied by the tissue of described tissue repair fibrous membrane manufactureReuse artifacts.
The present invention further provides described tissue repair fibrous membrane and tissue repair is usedGoods application in tissue repair.
The effect of invention
Compared with prior art, there is advantages that
(1) the tissue repair fibrous membrane of the present invention, has bigger serface, favorablyIn adhesion and the propagation of cell, and the surface topology of fiber is also beneficial to guideCell breaks up；
(2) the tissue repair fibrous membrane of the present invention has porous fluffy structure, and ratio is generalEnergising spins membrane structure and is more beneficial for fibrocyte and grows into rapidly, plays strengthening and fixingEffect, reaches the most preferable repairing effect；
(3) the tissue repair fibrous membrane quality of the present invention is light, soft, be more conducive toTight suture between tissue, improves the comfort of patient；
(4) the tissue repair fibrous membrane of the present invention, it is possible to reduce repair reuse artifacts wrinkleContracting, cause infect and with the generation of the situations such as tissue adhesion such as internal organs；
(5) the tissue repair fibrous membrane of the present invention is owing to can become without living cellsPoint, material source is abundant, and cost is relatively low, it is to avoid autologous, allosome material and dynamicThe source of thing source property material is not enough, and storage transport is simple；
(6) manufacturing approach craft of the fibrous membrane of the present invention is simple, and the production time is short,Can be prevented effectively from product in the course of processing to be contaminated, product quality is easily controllable, producesProduct standard easily realizes, and product can realize low cost, high efficiency industrialization produces.
Accompanying drawing explanation
Fig. 1 is the fluffy fiber film tangent plane scanning electron microscope (SEM) photograph that embodiment 4 obtains；
Fig. 2 is the electrospinning film tangent plane scanning electron microscope (SEM) photograph that embodiment 4 step (2) obtains；
Fig. 3 is the fluffy fiber film A that obtains of embodiment 4 and embodiment 4 step (2)The fiber of the electrospinning film B arrived is at 5000 × lower scanning electron microscope comparison diagram；
Fig. 4 is the fluffy fiber film A that obtains of embodiment 4 and embodiment 4 step (2)The fiber of the electrospinning film B arrived is at 10000 × lower scanning electron microscope comparison diagram；
Fig. 5 is the repairing effect figure of PP group month after operation in embodiment 7；
Fig. 6 is the PVDF1 group repairing effect figure of postoperative 6 months in embodiment 7；
Fig. 7 is the PVDF2 group repairing effect figure of postoperative 6 months in embodiment 7；
Fig. 8 is the PVDF2 group repairing effect figure of postoperative 6 months in embodiment 7；
Fig. 9 is the embodiment 7PCU group repairing effect figure of postoperative 6 months；
Figure 10 is the embodiment 9PLLA1 group pathology figure of postoperative 6 months；
Figure 11 is the embodiment 9PLLA2 group pathology figure of postoperative 6 months；
Figure 12 is animal derived group of the embodiment 9 pathology figure of postoperative 6 months；
Figure 13 is the embodiment 9PLLA1 group internal anatomy of postoperative 6 months；
Figure 14 is the embodiment 9PLLA2 group internal anatomy of postoperative 6 months；
Figure 15 is the postoperative internal anatomy of 6 months of animal derived group of embodiment 9.
Detailed description of the invention
The tissue repair fibrous membrane of the present invention is by the fiber of a diameter of 10nm ~ 100 μmSilk is interwoven, and has vesicular texture, and its loft is 200 ~ 2000cm3/g。
In the tissue repair fibrous membrane of the present invention, described filametntary diameter is preferably500nm~5μm。
The loft of the tissue repair fibrous membrane of the present invention is preferably600~1600cm3/g。
The pliability of the tissue repair fibrous membrane of the present invention is preferably 50 ~ 500 milli cattle, preferably 200 ~ 450 milli-newton.
The preferred average pore size of tissue repair fibrous membrane of the present invention is 50 ~ 500 μm.
The tissue repair fibrous membrane preferred thickness of the present invention is 0.5 ~ 1.0mm.
The preferred tensile strength of tissue repair fibrous membrane of the present invention is 20 ~ 80N/cm.
Loft of the present invention refers to the apparent thickness of fibrous membrane and the ratio of surface density1000 times, it may be assumed that
Loft B=apparent thickness T0/ surface density ω × 103
Loft is with cm3/ g represents, apparent thickness represents with mm, and surface density is with g/m2Represent.Apparent thickness T0Method of testing be utilize FAST 1 compressibility Fabric Style instrument according toGB/T 7689.1-2001 method is tested, and is expressed as fibrous membrane at 2cN/cm2PressureLower thickness (mm) and fibrous membrane are at 100cN/cm2The difference of thickness (mm) under pressure.FaceThe test mode of density ω is under the depth information ignoring fibrous membrane, measures single listPlane amass under weight.
Pliability of the present invention refers to test according to method in GB/T 8942-2002The maximum vector sum of frictional force at the counter-bending power of diaphragm out and diaphragm and gap,Representing with milli-newton, softness values the least explanation film is the most soft.
Heretofore described filament diameter is that the method by scanning electron microscope is measured's；Described average pore size is with reference to ASTM D 6767-2002, utilizes Capillary FlowPorosimetry is measured by Vesicular protein；Described tensile strength is to pass throughGB/T3923.1-1997 " finished tensile strength and the mensuration of elongation at break " method is enteredRow measures；Described thickness is according to GB/T by compressibility Fabric Style instrument7689.1-2001 method is measured.
As the manufacture method of tissue repair fibrous membrane of the present invention, including using electrostaticThe method of spinning process.
As a kind of preferable production process of tissue repair fibrous membrane of the present invention, permissibleUse electrostatic spinning technique to combine solvent dissolution method and carries out, specifically include following steps:
(1) by cellosilk materials different for two kinds of dissolution properties, it is dissolved in corresponding respectivelyIn solvent, obtain the cellosilk material solution of both of which one；
(2) the both of which one cellosilk material solution difference that will obtain in step (1)Loading in different electrostatic spinning syringes, the corresponding nozzle needle of two kinds of cellosilk materials existsOn high-tension electricity source plate evenly distributed, carry out electrostatic spinning, obtain two kinds of dissolution properties notThe fibrous membrane of the same crisscross intersection of cellosilk；
(3) according to the dissolution properties of cellosilk material, select suitable solvent by step(2) in, a kind of cellosilk in the fibrous membrane of preparation dissolves, and another then keeps notBecome, obtain described tissue repair fibrous membrane.
In above-mentioned steps (2), the preferably rate adaptation of micro-injection pump is 0.1 ~ 15.0ml/ hour, more preferably 3 ~ 6ml/ hour.
In above-mentioned steps (2), the preferably voltage-regulation of high tension generator is 5 ~ 45KV,More preferably 20 ~ 36KV.
In above-mentioned steps (2), the receiving range preferably receiving device is adjusted to 5.0 ~ 30.0Cm, more preferably 15.0 ~ 20.0cm.
In the present invention, the different cellosilk material of the two dissolution properties refers to, twoPlant only one of which cellosilk material in cellosilk material and can be dissolved in a certain solventIn.A kind of cellosilk material preferably wherein is: PCU(polycarbonate polyurethane)Or PVDF(polyvinylidene fluoride).Another kind of cellosilk material preferably wherein is:PLLA(L-polylactic acid) or PLGA(Poly(D,L-lactide-co-glycolide).
As the another kind of preferable production process of tissue repair fibrous membrane of the present invention, bagInclude following steps:
(1) cellosilk material is dissolved in solvent, obtains homogeneous cellosilk material moltenLiquid；
(2) the homogeneous cellosilk material solution obtained in step (1) is loaded electrostaticIn spinning syringe, carry out electrostatic spinning and obtain fiber, and fiber is received as membranaceousStructure, obtains fibrous membrane；
(3) by the fibrous membrane for preparing in step (2) after solvent supersonic is swellingState under, carry out pre-freeze at a predetermined temperature, then carry out vacuum lyophilization,Obtain tissue repair fibrous membrane.
In above-mentioned steps (2), the preferably rate adaptation of micro-injection pump is 0.1 ~ 15.0ml/ hour, more preferably 3 ~ 6ml/ hour.
In above-mentioned steps (2), the preferably voltage-regulation of high tension generator is 5 ~ 45KV,More preferably 30 ~ 36KV.
In above-mentioned steps (2), the receiving range preferably receiving device is adjusted to 5.0 ~ 30.0Cm, more preferably 15.0 ~ 20.0cm.
In above-mentioned steps (3), the fiber that preferably will prepare in step (2)After film concentration is the ethanol water infiltration of 50% ~ 95%, then carry out ultrasonic swelling.
In above-mentioned steps (3), the solvent for ultrasonic swollen fiber film is preferably injectionUse water.
In above-mentioned steps (3), the fiber that preferably will prepare in step (2)After film infiltrates in the ethanol water that concentration is 50% ~ 95%, put into and fill injectionIn the ultrasonic machine of water, stand after ultrasonic swelling 5 ~ 15 minutes, change water for injection, thenUltrasonic swelling, repeat operation, be replaced with water until ethanol is injected.SoAfter the fibrous membrane under ultrasonic for water for injection solvent swelling state put in freeze drying box in-50 DEG C carry out precooling 2 ~ 5 hours, are then turned on vacuum and carry out vacuum lyophilization20 ~ 26 hours, obtain described tissue repair fibrous membrane.
As another preferable production process of tissue repair fibrous membrane of the present invention, bagInclude following steps:
(1) cellosilk material is dissolved in solvent, obtains homogeneous cellosilk material moltenLiquid；
(2) the homogeneous cellosilk material solution obtained in step (1) is loaded electrostaticIn spinning syringe, carry out electrostatic spinning and obtain fiber, and fiber is received as membranaceousStructure, obtains fibrous membrane；
(3) by the fibrous membrane of preparation in step (2) along the transverse axis of fibrous membrane or the longitudinal axisOne of direction stretching, stop stretching after make fibrous membrane shape under this extended state；Then by fibrous membrane along the direction stretching vertical with above-mentioned draw direction of fibrous membrane, stopOnly make fibrous membrane shape under this extended state after stretching, obtain tissue repair fineDimension film.
In above-mentioned steps (2), the preferably rate adaptation of micro-injection pump is 0.1 ~ 15.0ml/ hour, more preferably 3 ~ 6ml/ hour.
In above-mentioned steps (2), the preferably voltage-regulation of high tension generator is 5 ~ 45KV,More preferably 30 ~ 36KV.
In above-mentioned steps (2), the receiving range preferably receiving device is adjusted to 5.0 ~ 30.0Cm, more preferably 15.0 ~ 20.0cm.
In above-mentioned steps (3), horizontal and vertical rate of extension is the most independently of one anotherIt is 50 ~ 400mm/min, more preferably 50mm/min ~ 200mm/min.
In above-mentioned steps (3), horizontal and vertical tensile elongation is the most independently of one anotherFor original length 1.5 ~ 6.0 times.
In above-mentioned steps (3), it is preferable that live in above-mentioned steps (2) with clipThe both sides of the fibrous membrane prepared, are set below materials hot deformation temperature by temperatureThe temperature of 0 DEG C ~ 30 DEG C, at the uniform velocity stretches with the speed of 50 ~ 400mm/min, makes fibrous membraneStop stretching after being elongated to 1.5 ~ 6.0 times of original length, make fibrous membrane at normal temperaturesShape under this extended state 1h ~ 4h, then takes off and by other the two of fibrous membraneWhile clamp with fixture, temperature is set below materials hot deformation temperature 0 DEG C ~ 30 DEG CTemperature, even with the speed of 50 ~ 400mm/min along the direction vertical with draw direction beforeSpeed stretching, makes fibrous membrane stop stretching after being elongated to 1.5 ~ 6.0 times of original length,Make fibrous membrane shape under this extended state 1h ~ 4h at normal temperatures, obtain described tissueReparation fibrous membrane.
The present invention also provides for the tissue repair fibrous membrane prepared by said method.
The filametntary material used in the tissue repair fibrous membrane of the present invention can beDegradation material, non-degradable material or a combination thereof.Degradation material can be synthesisDegradation material or natural macromolecular material；Non-degradable material is preferably poly-fluorine class materialMaterial, polypropylene based material or polyurethane material.
As degradation material, preferably polylactic acid (PLA) (particularly PLLA(PLLA)), polycaprolactone (PCL), polyglycolic acid (PGA), polylactic acid-Co-glycolic acid (PLGA) or 1,3-glycol polymers (PDO), collagen eggIn vain, gelatin, fibrin, fibroin, the peptide polymer of elastin mimicry, shellPolysaccharide, modification of chitosan.
As poly-fluorine class material, preferably polyvinylidene fluoride (PVDF) or polytetrafluoroethyl-neAlkene (PTFE).
As polypropylene based material, preferably syndiotactic polypropylene.
As polyurethane material, optimization polyurethane (PU), polycarbonate polyurethane(PCU), polyether based polyurethanes or silicane-modified polyurethane (SPU).
The present invention also provides for described tissue repair fibrous membrane in the tissue repair system of manufactureApplication in product.Preferably, the tissue repair fibrous membrane of the present invention is used for manufacturing herniaGas repairs sticking patch, female pelvic floor dysfunctional disease repair system (includes repairing at the bottom of basinMultiple sticking patch or urinary incontinence suspender or fistula patch), artificial bone-head for shoulder's sleeve, hard brain (ridge) filmRepair sticking patch, artificial skin, pericardium sticking patch, artificial blood vessel, artificial nerve catheter,Artificial tooth's film, artificial ligament, artificial heel string, Bone Defect Repari (filling) product etc..
The present invention further provides and repaiied by the tissue of described tissue repair fibrous membrane manufactureReuse artifacts.
The tissue repair goods of the present invention, preferably hernia repair sticking patch, women basinEnd functional disorder disease repair system (includes pelvic floor repairing patch or urinary incontinence suspentionBand or fistula patch), artificial bone-head for shoulder's sleeve, hard brain (ridge) film healing sticking patch, artificial skin,Pericardium sticking patch, artificial blood vessel, artificial nerve catheter, artificial tooth's film, artificial ligament,Artificial heel string, Bone Defect Repari (filling) product etc..
The present invention further provides described tissue repair fibrous membrane and tissue repair is usedGoods application in tissue repair.Described tissue repair fiber is preferably providedFilm and tissue repair goods are used for hernia repair, female pelvic dysfunction diseaseSick treatment (is repaiied including, but not limited to reparation or the treatment of urinary incontinence or fistula at the bottom of basinAgain), the reparation of shoulder sleeve, hard brain (ridge) film healing, skin tissue recovering, pericardium are repaiiedAgain, vascular repair, nerve trachea reparation, tooth film healing, ligament repair, heel string are repaiiedAgain, the application in Bone Defect Repari (filling).
The present invention is further described below in conjunction with specific embodiment.The present invention implementsThe reagent of example employing and raw material unless stated otherwise, are all commercial conventional products.
Embodiment
Embodiment 1
(1) by polycarbonate polyurethane (PCU), it is dissolved in DMFWith the mixed solvent of oxolane, making the concentration of PCU in solution is 12g/100mL,DMF is 1:1 with the mixed proportion (volume ratio) of oxolane,To homogeneous cellosilk material solution.
PLLA is dissolved in hexafluoroisopropanol (HFIP) solution, makes PLLA in solutionConcentration be 5g/100mL, obtain homogeneous cellosilk material solution.
(2) cellosilk material solution homogeneous for above two is respectively charged into two electrostaticIn spinning syringe, the corresponding nozzle needle of bi-material is evenly distributed on high-tension electricity source plate,The speed of regulation micro-injection pump is 6ml/ hour, the voltage of regulation high tension generatorFor 22KV, it is 20cm that regulation receives the receiving range of device, by bi-materialElectrostatic cospinning prepares two kinds of different crisscross intersections of cellosilk material of dissolution properties simultaneouslyFibrous membrane, reach to close after 0.5mm thickness electrostatic spinning.
(3) film that will take off, puts into ultrasonic swelling, dissolving in hexafluoroisopropanol solvent6 hours, making PLLA material dissolve completely, PCU material then keeps constant, from solventThe material that middle taking-up is not dissolved, i.e. obtains tissue repair fibrous membrane.
In embodiment 1, the average fibre diameter of gained tissue repair fibrous membrane is 2 μm,Film thickness is 0.5mm, and average pore size is 350 μm, and tensile strength is 25N/cm, fluffyLooseness is 970cm3/ g, pliability is 250 milli-newton.
Embodiment 2
(1) polyvinylidene fluoride (PVDF) is dissolved in the N that volume ratio is 4:6, N-The mixed solvent of dimethylformamide/acetone, makes the PVDF concentration in the solution be18g/100mL；PLLA (PLLA) is dissolved in hexafluoroisopropanol (HFIP) moltenIn liquid, making the concentration of PLLA in solution is 5g/100mL, obtains homogeneous cellosilkMaterial solution.
(2) cellosilk material solution homogeneous for above two is respectively charged into two electrostaticIn spinning syringe, the corresponding nozzle needle of bi-material is evenly distributed on high-tension electricity source plate,The speed of regulation micro-injection pump is 5ml/ hour, and the voltage of regulation high tension generator is22KV, it is 20cm that regulation receives the receiving range of device, same by bi-materialShi Jing electricity cospinning prepares two kinds of different crisscross intersections of cellosilk material of dissolution propertiesFibrous membrane, closes electrostatic spinning after reaching 0.5mm thickness.
(3) film that will take off, puts into ultrasonic swelling, dissolving in hexafluoroisopropanol solvent6 hours so that it is middle PLLA material is completely dissolved, prepared tissue repair fibrous membrane.
The average fibre diameter of described tissue repair fibrous membrane is 3 μm, and film thickness is0.5mm, average pore size is 450 μm, and tensile strength is 35N/cm, and loft is 1640cm3/ g, pliability is 400 milli-newton.
Embodiment 3
(1) PVDF material is dissolved in the N,N-dimethylformamide that volume ratio is 4:6/ acetone mixed solvent, making PVDF concentration in the solution is 18g/100mL；It is prepared intoTo homogeneous cellosilk material solution.
(2) the cellosilk material solution obtained in step (1) is loaded electrostatic spinningIn syringe, the speed of regulation micro-injection pump is 6ml/ hour, regulates high Hair FixerThe voltage of raw device is 30KV, and it is 20cm that regulation receives the receiving range of device, carries outElectrostatic spinning obtains fiber, and fiber is accepted as membrane structure, spins to thicknesses of layersClose electrostatic spinning after being about 0.5mm, obtain fibrous membrane.
The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5Mm, average pore size is 190 μm, and tensile strength is 43N/cm, and loft is 170cm3/ g, pliability is 930 milli-newton.
(3) by molten at the ethanol that concentration is 95% for fibrous membrane prepared in step (2)Complete wetting in liquid, then takes out the fibrous membrane after ethanol solution infiltration, puts into and fillIn the ultrasonic container of water for injection, make fibrous membrane be fully immersed in water for injection, openOpen ultrasonic, power 90W, ultrasonic 10 minutes, after standing 5 ~ 10 minutes, changes ultrasonicWater for injection in container, is then turned on ultrasonic, power 90W, ultrasonic 10 minutes, asThis repetitive operation 7 ~ 8 times, to solution, ethanol is replaced complete.Then take out injectionWith water ultrasonic swelling after fibrous membrane, be put in the freeze drying box of-50 DEG C and carry out pre-coolingFreeze 4 hours, be then turned on vacuum lyophilization, make the fibrous membrane vacuum freezing of precooling doDry 24 hours, obtain tissue repair fibrous membrane.
The average fibre diameter of described tissue repair fibrous membrane is 2 μm, and film thickness is0.6mm, average pore size is 400 μm, and tensile strength is 48N/cm, and loft is 1530cm3/ g, pliability is 420 milli-newton.
Embodiment 4
(1) PLLA (PLLA) material is dissolved in hexafluoroisopropanol solvent,Making PLLA concentration in solution is 6g/100mL, prepares homogeneous cellosilk materialSolution.
(2) the cellosilk material solution prepared in step (1) is loaded electrostatic spinningIn syringe, the speed of regulation micro-injection pump is 6ml/ hour, regulates high Hair FixerThe voltage of raw device is 20KV, and it is 15cm that regulation receives the receiving range of device, carries outElectrostatic spinning obtains fiber, and fiber is accepted as membrane structure, spins to thicknesses of layersClose electrostatic spinning after being about 0.5mm, obtain fibrous membrane.
The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5Mm, average pore size is 115 μm, and tensile strength is 33N/cm, and loft is 130cm3/ g, pliability is 870 milli-newton.
(3) both sides of fibrous membrane are then clamped with fixture, under the conditions of temperature is 60 DEG CAt the uniform velocity stretch with the speed of 100mm/min, make fibrous membrane be elongated to original lengthStop stretching after 3 times, make fibrous membrane shape under this extended state 4h at normal temperatures,Then take off fibrous membrane and clamp the other both sides of fibrous membrane with fixture, in temperature beingUnder the conditions of 60 DEG C, along the direction vertical with draw direction before with the speed of 100mm/minRate at the uniform velocity stretches, and makes fibrous membrane stop stretching after being elongated to 3 times of original length,Make fibrous membrane shape under this extended state 4h under room temperature, obtain tissue repair fineDimension film.
The average fibre diameter of described tissue repair fibrous membrane is 2 μm, and film thickness is0.6mm, average pore size is 450 μm, and tensile strength is 50N/cm, and loft is 1100cm3/ g, pliability is 400 milli-newton.
Embodiment 5
(1) PVDF material is dissolved in the N,N-dimethylformamide that volume ratio is 4:6/ acetone mixed solvent, making PVDF concentration in the solution is 18g/100mL；It is prepared intoTo homogeneous cellosilk material solution；
(2) the cellosilk material solution obtained in step (1) is loaded electrostatic spinningIn syringe, the speed of regulation micro-injection pump is 6ml/ hour, regulates high Hair FixerThe voltage of raw device is 30KV, and it is 20cm that regulation receives the receiving range of device, carries outElectrostatic spinning obtains fiber, and fiber is accepted as membrane structure, spins to thicknesses of layersClose electrostatic spinning after being about 0.5mm, obtain fibrous membrane.
The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5Mm, average pore size is 190 μm, and tensile strength is 43N/cm, and loft is 170cm3/ g, pliability is 930 milli-newton.
(3) both sides of fibrous membrane are then clamped with fixture, under the conditions of temperature is 95 DEG CAt the uniform velocity stretch with the speed of 100mm/min, make fibrous membrane be elongated to original lengthStop stretching after 2.5 times, make fibrous membrane shape 4 under this extended state at normal temperaturesH, then takes off fibrous membrane and clamps the other both sides of fibrous membrane with fixture, in temperature beingUnder the conditions of 95 DEG C, along the direction vertical with draw direction before with the speed of 100mm/minRate at the uniform velocity stretches, and makes fibrous membrane stop stretching after being elongated to 2.5 times of original length,Make fibrous membrane shape under this extended state 4h at normal temperatures, obtain tissue repair and useFibrous membrane.
The average fibre diameter of described tissue repair fibrous membrane is 2 μm, and film thickness is0.6mm, average pore size is 400 μm, and tensile strength is 65N/cm, and loft is 1300cm3/ g, pliability is 450 milli-newton.
Embodiment 6
(1) PCU material is dissolved in N,N-dimethylformamide that volume ratio is 1:1/Oxolane mixed solvent, making PCU concentration in the solution is 12g/100mL；SystemFor obtaining homogeneous cellosilk material solution；
(2) the cellosilk material solution obtained in step (1) is loaded electrostatic spinningIn syringe, the speed of regulation micro-injection pump is 5ml/ hour, regulates high Hair FixerThe voltage of raw device is 36KV, and it is 25cm that regulation receives the receiving range of device, carries outElectrostatic spinning obtains fiber, and fiber is accepted as membrane structure, spins to thicknesses of layersClose electrostatic spinning after being about 0.5mm, obtain fibrous membrane.
The average fibre diameter of the fibrous membrane herein obtained is 2 μm, and film thickness is 0.5Mm, average pore size is 160 μm, and tensile strength is 52N/cm, and loft is 110cm3/ g, pliability is 510 milli-newton.
(3) both sides of fibrous membrane are then clamped with fixture, under the conditions of temperature is 80 DEG CAt the uniform velocity stretch with the speed of 100mm/min, make fibrous membrane be elongated to original lengthStop stretching after 2.0 times, make fibrous membrane shape 6 under this extended state at normal temperaturesH, then takes off fibrous membrane and clamps the other both sides of fibrous membrane with fixture, in temperature beingUnder the conditions of 80 DEG C, along the direction vertical with draw direction before with the speed of 100mm/minRate at the uniform velocity stretches, and makes fibrous membrane stop stretching after being elongated to 2.0 times of original length,Make fibrous membrane shape under this extended state 6h at normal temperatures, obtain tissue repair and useFibrous membrane.
The average fibre diameter of described tissue repair fibrous membrane is 2 μm, and film thickness is0.5mm, average pore size is 260 μm, and tensile strength is 60N/cm, and loft is 230cm3/ g, pliability is 470 milli-newton.
The application in hernia repair of embodiment 7 fibrous membrane
By the tissue repair fibrous membrane prepared in embodiment 1, embodiment 5, embodiment 5The fibrous membrane prepared in step (2) and the polypropylene mesh used clinically(3DMAXTMThe sample that Mesh is provided by the second Affiliated Hospital of Zhongshan University), cut outBe cut into 3.5cm × 6cm, clean, sterilizing, be respectively prepared PCU hernia repair sticking patch (byThe fibrous membrane manufacture of embodiment 1), the PVD F1 hernia repair sticking patch (fibre by embodiment 5Dimension film manufacture), PVDF2 hernia repair sticking patch (obtains by embodiment 5 step (2)Fibrous membrane manufacture) and PP hernia repair sticking patch (being manufactured by polypropylene mesh).
Above-mentioned hernia repair sticking patch is carried out new zealand rabbit experiment.New zealand rabbit, body weight2.5-2.8Kg, age 6-12 month, totally 60.Experimental rabbit is randomly divided into 4 groups,Being respectively PCU group, PVD F1 group, PVDF2 group and PP group, often group 15 experiment is dynamicThing.The animal entering experiment is anaesthetized, preserved skin, lies on the back Baoding on plank；After sterilization paving is single；Hit exactly in abdominal part, cut skin with 4# scalpel along rabbit hunter's line,It is about 8cm, exposes muscle, the stomach wall holostrome that size is 2cm × 5cm (is included abdomenFilm, muscle, fascia tissue) excision；PCU group, PVDF1 group, PVDF2 group,PP group is respectively adopted PCU hernia repair sticking patch, PVDF1 hernia repair sticking patch, PVDF2Hernia repair sticking patch and PP hernia repair sticking patch, with 0# silk thread by the flesh of sticking patch Yu surroundingMeat interrupted suture.4# wire discontinuous sewing skin.
The postoperative observation that animal is carried out routine and nursing.PCU group in observation period,PVDF1 group and the feed water inlet of PVDF2 group all animals are normal, and wound healing is good,Have no that infection and abdominal part hernia are formed.PP group 5 animals the 5th ~ 7 day incision after surgeryProtuberance occur, 3 animals are dead in postoperative 7th ~ 10 day, and when dissected finds that sticking patch is with interiorThe serious adhesion of dirty generation.Remaining animal all survived to the time of drawing materials.
Month after operation, often organizes 5 animals by PCU group, PVDF1 group, PVDF2 groupDissect, 4 zootomies of PP group.Touch operative site, PCU group and PVDF1 group handsArt position touches softness.It is the hardest that PVDF2 group touches relatively PVDF1 group.Along sticking patch edgeMore than 2cm cuts Musclar layer, and naked eyes are visible, PCU group, PVDF1 group and PVDF2Group sticking patch is with internal organs all without adhesion, and blood capillary is grown into along sticking patch edge to centre, newlyRaw tissue covers whole sticking patch substantially.Under mirror, result shows, PCU group, PVDF1Visible substantial amounts of fibroblast and collagen fiber hyperplasia around group, PVDF2 group sticking patch,Minority lymphocytic infiltration (≤25/HPF), more blood capillary proliferation (5-10/ HPF).And under mirror, PCU group, PVDF1 group blood capillary are many compared with PVDF2 group, poorDifferent statistically significant (P < 0.05).Visible PCU group sticking patch, PVDF1 group sticking patch,PVDF2 group sticking patch has preferable histocompatibility；Wherein PCU group sticking patch andThe loft that PVDF1 group sticking patch is higher is more beneficial for tissue and grows into.
PP group touches operative site, and sensation relatively other three groups is hard, can be clearly felt that differentThe existence of thing.Cut skin, it is seen that the cambium of thin layer covers at sticking patch tableFace, but with sticking patch easily openable.Around sticking patch, 2cm cuts Musclar layer, and naked eyes are visiblePP group sticking patch and the serious adhesion of internal organs, and it is not readily separated (Fig. 5).Under mirror, result shows,Having inside PP group sticking patch in more cavity, around there are a small amount of fibroblast and glue in cavityOriginal shape becomes, it is seen that small amount blood capillary proliferation (≤2/HPF), a large amount of foreign bodies are big and smallBorn of the same parents and lymphocytic infiltration, it is seen that PP group sticking patch histocompatibility is poor, be unfavorable for thinBorn of the same parents adhere to, and rejection and immunization inflammatory reaction are obvious.
3 months after operation, PP group 4 animals of dissection, remaining group often group dissects 5.CutTissue in the range of sticking patch and about 2cm.PCU group, PVDF1 group operative site touchTouch softness, close with autologous tissue.It is methodically arranged between sticking patch and skin, easily separated,Sticking patch and internal organs are grown into inside sticking patch without any adhesion, a large amount of cambiums.MirrorLower result shows, is tightly combined with collagen fiber and fibrocyte around sticking patch；Sticking patchInternal visible substantial amounts of collagen fiber, with a small amount of blood capillary (3-5/HPF).PVDF2 group material surgical position touches relatively soft, is methodically arranged between sticking patch and skin,Easily separated, sticking patch and internal organs, without any adhesion, cut inside sticking patch, newborn groupKnit less.Under mirror, result shows, more collagen fiber seen from sticking patch only surface, sticking patchInside has no cambium, it is seen that cambium is grown into slower inside PVDF2 diaphragm.
PP group touches operative site, feels harder, can be clearly felt that the existence of foreign body.PP group patch faces has the cambium of layer, lacks unity and coherence with skin, is difficult toSeparating, close to internal organs, there is serious adhesion with internal organs in sticking patch, difficulty or ease are torn, intestinalSwelling.Under mirror, result shows, has a small amount of fibroblast and collagen to be formed around sticking patch,With small amount blood capillary proliferation (≤2/HPF)；A large amount of foreign-body giant cells and lymphCellular infiltration, illustrates that rejection and immunization inflammatory reaction are obvious.
Postoperative 6 months, PP group dissected 4 animals, and remaining group often group dissects 5.CutTissue in the range of the sticking patch of mend and about 2cm.PVDF1 group and PCU group handsArt position touches the most soft, and as shown in Fig. 6 and Fig. 9, sticking patch melts with cambiumIt is integrated, it is more difficult to distinguish cambium and sticking patch, cambium and skin interbedSecondary clear, easily separated, cambium and internal organs are without any adhesion.Microscopic observationResult shows, implants and is tightly combined with collagen fiber and fibrocyte around sticking patch position；Internal visible substantial amounts of collagen fiber.PVDF2 group operative site touches relatively soft, asShown in Fig. 7 and Fig. 8, still can tell sticking patch and cambium, cambium and skinBetween be methodically arranged, easily separated, sticking patch and internal organs are without any adhesion.Microscopic observationResult shows, more collagen fiber sticking patch seen from patch faces, cuts inside sticking patch,Cambium is the most less.
PP group touches operative site, feels harder, hence it is evident that feel the existence of foreign body.PP group lacks unity and coherence with skin, it is impossible to separate；Serious with internal organs adhesion；Under mirrorObserved result shows, only has a small amount of fibroblast and collagen to be formed around sticking patch, tableA small amount of blood capillary proliferation (≤5/HPF), a large amount of foreign-body giant cells and lymph seen from faceCellular infiltration, foreign body reaction and immunologic rejection are serious；Illustrate that PP group sticking patch is unfavorable for carefullyThe adhesion of born of the same parents and growing into, histocompatibility and repairing effect are poor.
The application in repairing at the bottom of basin of embodiment 8 fibrous membrane
Use and prepared, by embodiment 3, the pelvic floor repairing patch (PVDF3 that fibrous membrane manufacturesSticking patch), embodiment 3 step 2 prepare fibrous membrane manufacture pelvic floor repairing patch (PVDF4Sticking patch), embodiment 6 prepare fibrous membrane manufacture pelvic floor repairing patch (PCU 1 sticking patch)Pelvic floor repairing patch (PP sticking patch, the Johnson & Johnson Prolift manufactured with polypropylene materialTM,Guangzhou overseas Chinese hospital provides) carry out miniature pig experiment.All sticking patch are cut into 2cm × 2cmSize.Selection 20～25kg, the female miniature pig of sexual maturity 8, PVDF3 group, PVDF4Group, PCU1 group and PP group totally 4 groups, often group 2.The miniature pig entering experiment is implementedGeneral anesthesia, through hypogastric region stomach wall approach, exposes bladder, uterus and vagina epimere.To mendSheet is respectively implanted between vesicovaginal space, and silk thread is fixed.PVDF3 group, PVDF4Group, PCU1 group and PP group as a control group are respectively adopted PVDF3 sticking patch, PVDF4Sticking patch, PCU1 sticking patch and PP sticking patch.The postoperative nursing that animal is carried out routine and observation.In all laboratory animal observation periods, all performance is good, and wound healing is good, without implantEvict from, exposure etc. occurs.Postoperative feed water inlet is normal, all survives to the time of drawing materials.
Postoperative 4 weeks, cut the vesicovaginal space tissue including pelvic floor repairing patchSpecimen.Touch operative site with hands, PVDF3 group, PVDF4 group, PCU1 sticking patch andIn PP group, PP material is the hardest, and PVDF4 group material takes second place, PCU1 group material softness,PVDF3 group material is the most soft and flexible, PVDF3 group, PVDF4 group, PCU1 groupPatch faces covers one layer of newborn epithelium, sticking patch and cambium not easily openable, naked eyesThe blood capillary of visible new life, PP group patch faces also covers one layer of cambium, mendsSheet easily separates with cambium.Pathological examination shows, PVDF3 group sticking patch inside and tableThere are a large amount of fibroblast and collagen fiber hyperplasia in face, has more capillary inside sticking patchBlood vessel (5-10/HPF), it is seen that cambium has been grown into inside diaphragm, andGrow into very fast.PCU1 group, PVDF4 group surface have more fibroblast and collagen fineDimension, the internal visible a small amount of fibroblast of sticking patch and collagen fiber hyperplasia, Shao LiangmaoThin blood vessel hyperplasia (3-5/HPF), illustrate that cambium diaphragm of growing into is internal but growEnter slower.The internal visible minority lymphocytic infiltration of PVDF4 group, has slight exempting fromEpidemic disease inflammatory reaction.More fibroblast and collagen is had around PP group sticking patch, lessAmount blood capillary (2-3/HPF), a small amount of foreign-body giant cell (≤3/HPF), canSee that cambium cannot be integral with diaphragm length, repair relatively slow, and have foreign material repulsion anti-Should.
12 weeks after operation, cuts include repairing the vagina including implant and bladder mark at the bottom of basinThis.Touch with hands, in PVDF3 group, PVDF4 group, PCU1 group and PP group, PPMaterial is the hardest, and PVDF4 material takes second place, and repairing position has relatively with surrounding tissue flexibilitySignificant difference；PCU1 material soft-touch, PVDF3 is the most soft and flexible.PVDF3The all visible a large amount of fibroblasts in group patch faces and inside and collagen, and sticking patch and lengthThe tissue shape gone out is integrated, it is impossible to differentiates and peels off.Microscopic observation result shows, implantsIt is tightly combined with collagen fiber and fibrocyte around sticking patch position, it is impossible to distinguish new lifeTissue and diaphragm material, internal visible substantial amounts of collagen fiber, cambium is the most completeIntegral with diaphragm length, it is achieved Regeneration and Repair.PCU1 group sticking patch is difficult to cambiumPeeling off, naked eyes are visible, and cambium is grown into material internal, material and cambium itBetween be difficult to differentiate between.Microscopic observation result shows, there is a large amount of fibroblast on surface and lacksAmount angiogenesis (3-5/HPF), internal visible small amount blood capillary (2-3Individual/HPF).PVDF4 group sticking patch and cambium can be peeled off, and there is more one-tenth fiber on surfaceCell and a small amount of angiogenesis (3-5/HPF), internal visible small amount capillaryBlood vessel (≤2/HPF).PP group patch faces also shows more fibroblast and relativelyA small amount of angiogenesis (2-3/HPF), but sticking patch is with the tissue grown relativelyIt is easily peeled, it is seen that cambium cannot be integral with diaphragm length, and repairing effect is poor.
Cell and tissue are quickly adhered to implant sticking patch by the loft of visible implantation sticking patchSurface also enters material internal and plays an important role, and the high-loft of sticking patch and softnessProperty be more beneficial for cambium and material and form one；Loft is less, then newborn groupKnit inside diaphragm of growing into slower.
The application in cerebral dura mater is repaired of embodiment 9 fibrous membrane
By the tissue repair fibrous membrane prepared in embodiment 4, embodiment 4 step (2)In prepare fibrous membrane be cut into 4cm × 6cm, clean, sterilizing, be respectively prepared PLLA1Cerebral dura mater repairs sticking patch (by the fibrous membrane manufacture of embodiment 4), PLLA2 cerebral dura mater is repaiiedMultiple sticking patch (the fibrous membrane manufacture by obtaining in embodiment 4 step (2)), matched group is adoptedWith commercialization use clinically animal derived duramater reparation sheet (meninges be good for,Sample is provided) by Affiliated Hospital of Zhongshan University the 3rd.
Selecting healthy dogs 6, male and female do not limit, and between body weight 10-15kg, the observation period is2-3 month.The dog entering experiment implements general anesthesia, and Double Tops open cranium, artificial manufacture bilateral portionPoint dura defect and brain tissue impairment, then with PLLA1 cerebral dura mater repair sticking patch withAnd PLLA2 cerebral dura mater repairs sticking patch and implementing respectively firmly with an experimental dog brain left and right sidesMeninges kposthesis, 3 dogs of parallel test.Sticking patch and right is repaired with PLLA2 cerebral dura materAnimal derived meninges patch according to group is the most real same the experimental dog brain left and right sidesExecute dural repair, 3 dogs of parallel test.Postoperative dog is carried out routine nursing andObserving, repairing sticking patch position collect specimen when each observation expires, paired observation is bigBody specimen and mirror undertissue.Each experimental animal feeding to set time after anesthetized animal,Exposing skull by aforementioned cranium mode of opening, separate to expose and repair sticking patch outer surface, vein is notedEnter air and put to death animal, raise after cutting skull to cut and repair sticking patch and tissue around.Perusal repairs sticking patch outer surface, quality and the relation of surrounding tissue, with or without capsuleThe adhesion situation of swollen, scleroma and inner surface and cerebral tissue.Specimen is bottled, and is soaked in good fortuneThat Malin's fixative, labels Specimen bottle.After under room temperature, formalin fixes 1 week,Take operative site local organization, routine paraffin wax Bao Li, HE tissue section strain.
6 dogs of Post operation recover good, and wound healing is good, without secretions.Postoperative enterFood, water inlet is normal, and the outdoor activities of dog are normal, do not find the dyskinesia.3 monthsPush air in posterior vein and put to death dog, centered by operative site, more than SurgeryPosition 1cm scope cuts specimen so that it is include repairing sticking patch and periphery cerebral dura mater and inner faceCerebral tissue.After cutting out specimen, successively separate brain bone and meninges, it is seen that PLLA1The meninges that cerebral dura mater repairs sticking patch implant site is complete, fiber completely at sticking patch implantationTissue replaces, do not see at embedded material, and implantation meninges inner surface without adhesion, withCorrespondence cerebral tissue smooth surface, without adhesion.Repairing effect is as dissected picture Figure 13 instituteShowing, pathological picture is as shown in Figure 10；PLLA2 cerebral dura mater repairs sticking patch implant siteMeninges is complete, it is seen that part embedded material has been cracked into fragment, forms new fibreDimensional tissue, there is a little adhesion on corresponding cerebral tissue surface, and repairing effect is as dissectedShown in picture Figure 14, pathological picture is as shown in figure 11.And control animals source property meningesRepair sticking patch implant site still visible complete undegraded implantation sticking patch, and brain at implantationThere is more adhesion in film inner surface and cerebral tissue, can cause the ectopic discharge such as cerebral tissue,The complication such as epilepsy, repairing effect as dissected shown in picture Figure 15, pathological pictureAs shown in figure 12.
The application in skin repair of embodiment 10 fibrous membrane
The tissue repair fibrous membrane prepared in embodiment 4 is cut into 5cm × 5cm, clearlyWashing, sterilizing is made artificial skin and is carried out zoopery.Experimental rabbit body weight 2-2.5kg, yearIn 6-8 month age, male and female do not limit, totally 12.It is randomly divided into two groups of (experimental group and comparisonsGroup), often group 6.After the anesthesia of rabbit auricular vein, animal is placed on special-purpose operating table,Then for hair and sterilization.With scalpel, back full thickness skin is excised: excision area is4*4cm.Then artificial dermis is attached: experimental group sticks by embodiment 4 in wound siteFibrous membrane prepare artificial skin, fix at interval of 1cm suture.Matched group doesBlank processes.Experimental group and matched group cover one layer of aseptic oil respectively on woundYarn and sterile gauze, fix with surrounding skin with suture.
Post operation is observed animal and is taken food with or without normal, drinking-water, and body temperature respectively organizes coveringThe time separated with wound surface and other physiological activity situation, and observe repairing of wound surfaceMultiple situation.
Postoperative 2nd, 4,8 weeks often group take 2 rabbits and put to death, take the whole wound surface in back andNeighbouring normal skin, formalin is fixed, and carries out HE dyeing, light Microscopic observation coriumThe newborn situation of middle tissue, inflammatory reaction situation, the thickness of epidermal structure and appendagesRegeneration situation.
Matched group rabbit after surgery all wound surface all with oil yarn or gauze adhesion.Adjuvant hasObscission.Wound surface is hemorrhage, has a large amount of tissue fluid to ooze out.Wound surface heal completely after inLinear crust.Experimental group postoperative wound surface is dried, with oil yarn and gauze without adhesion, and between wound surfaceLaminating is closely.Wound is without red and swollen warm, and animal skin allergy does not occurs or infects phenomenon.MaterialMaterial covers lower without necrosis phenomena.Wound is rectangular crust after healing completely.Pass through microscopeObserving healing mouth skin prickle cell layer to thicken, basal cell hyperplasia enlivens, epidermal areaHorny layer, granular layer stratum spinosum and basal layer are the most visible.Skin corium appendages pipe, antiperspirantGland, the structure such as hair follicle is visible, it is seen that a large amount of fibroblasts are parallel to skin surface rowRow, the most more blood capillary proliferation, a small amount of lymphocytic infiltration in local.
Observation indicate that: the anti-infection ability of experimental group, prevent the work that wound surface is hemorrhageWith being better than matched group.Experimental group wound surface has no red and swollen, downright bad.Histological observation showsThe artificial skin material prepared by the fibrous membrane of embodiment 4 promotes skin texture Regenerated energyPower is better than matched group.
The application in bone is filled of embodiment 11 fibrous membrane
The tissue repair fibrous membrane prepared in embodiment 2 is cleaned, sterilizing, make boneRecovery support carries out rabbit zoopery.3 new zealand rabbits, body weight 2.5 ± 0.5Kg, itsIn female 1, male 2.Preserved skin after general anesthesia, is placed in animal on special-purpose operating table,Ventricumbent position, uses povidone iodine alcohol disinfecting, completes aseptic dressing, and towel clamp towel forceps fixes.CutOpen rabbit leg skin, use detacher separation periosteum, expose tibia hone lamella, with at a high speedBone drill manufactures rabbit defect of tibial, and defect size is 1cm × 2cm, will be by embodiment 2Fibrous membrane prepare bone repairing support fan-folded fill at defect, adjust fillThing height so that it is concordant with Cranial defect face, sews up.Postoperative 14 days, perusal boneGirder is thicker, the newborn eburnation of ultrasonic bone density instrument detection, and has more volumeKnit bone formation.3 months after operation, there is callus formation on the surface, bone hole of defect.Tap callus,Quality is hard, similar to normal bone tissues hardness, and callus color and autologous bone colorUnanimously.NIP reaction during rehabilitation.Postoperative animal recovers good, and feed water inlet is justOften.After extremity motor function gradually recovers, do not find the dyskinesia.
Above example be enough to illustrate that the fibrous membrane loft of the present invention is 200cm3/ g～2000cm3The beneficial effect that/g is brought, can be summarized as follows:
As can be seen from the above table, loft controls at 200cm3/ g～2000cm3The group of/gKnit reparation sticking patch, cambium can be formed with inducing cell fast-growth in sticking patch,Reach repairing effect.Again it can be seen that for degradation material (PLLA),Loft is at 200cm3/ g～2000cm3Sticking patch in/g range, with loft not at thisIn the range of sticking patch compare, faster, material degradation is faster for repairing effect.Further,After the surgical repair that pliability is 50 ~ 500 milli-newton scopes, repair the relative of positionSoftness significantly improves postoperative comfort.