CN1175910C - Method for modifying tissue material utilized in surgical implantation and modified material - Google Patents
Method for modifying tissue material utilized in surgical implantation and modified material Download PDFInfo
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Abstract
The present invention relates to a modification method of heterolysis or homogeneous tissue material chemistry used for surgery implantation and a tissue material prepared by the method, particularly to a modification processing method for artificial biological heart valve material and a valve material of modification processing. The calcification-resistant performance and the fatigue-resistant performance are obviously enhanced, and thus, the tissue material has longer service life.
Description
Technical field
The present invention relates to be used for xenogenesis or the method for homologue materials chemistry modification and the organization material for preparing with this method that surgery is implanted, especially the valve material handled of the modification processing method of artificial biological heart valve material and modification, its calcification and fatigue performance obviously strengthen, thereby have longer service life.
Background technology
Valvular heart disease is modal heart disease, and its morbidity accounts for whole cardiopathic half [1].The late period of this class disease, the patient that the valve pathological changes is serious, final effectively treatment has only changes lobe.According to nearest data, the patient that heart valve replacement surgery is accepted in the whole world every year 100000 was increased to present 300,000 [2] before 10 years.In China, by the investigation during " eight or five ", the existing rheumatic heart patient in the whole nation surpasses 2,500,000 [3].Along with the development of department of cardiac surgery, changing lobe has become routine operation, so these late results of changing the lobe postoperative patient depend primarily on artificial valve's quality.
Cardiac valve prosthesis is divided into mechanical prosthetic valve and bioprosthetic valve two big classes, their research nearly 40 years course of having passed by.Along with to mechanical prosthetic valve and bioprosthetic valve pluses and minuses understanding different separately, several several volts also appearred in artificial valve's development and clinical practice thereupon.The sixties, mechanical prosthetic valve and bioprosthetic valve are come out one after another, and all use in clinical.At the beginning of the seventies, it is found that severe complications such as thrombosis, thromboembolism can appear in mechanical prosthetic valve, meanwhile, have invented Carpentier glutaraldehyde modification technology, thereby have made the application of bioprosthetic valve surpass mechanical prosthetic valve.After entering the eighties, along with the development of the effective anticoagulant means of postoperative and the significant improvement in the mechanical prosthetic valve design, the i.e. appearance of bilobed flap, so that the end of the eighties, the application of mechanical prosthetic valve significantly increases, but the artificial lobe of two classes still comes into one's own equally on the whole, and is in the parallel development state.After entering the nineties, (with St.Jude is the bilobed flap of representative though mechanical prosthetic valve has almost reached impeccable stage on design and processing technology, blade is thin, open angle is big, hydrodynamic performance is almost close with bioprosthetic valve), various types of mechanical prosthetic valves have nearly 20 kinds more than, but finally still fail to solve the long-term anticoagulant difficult problem of postoperative.
Bioprosthetic valve is that organization material is made with bovine pericardium or porcine aortic valve generally, and recently, U.S. FDA has been confirmed the ideal material of bovine pericardium as artificial biological heart valve.Compare with mechanical prosthetic valve, bioprosthetic valve has good hemodynamic performance and biocompatibility, therefore, change the lobe postoperative patient and need not long-term anticoagulant therapy, have higher quality of life, this advantage is that mechanical prosthetic valve is incomparable always, therefore, people post with more expectations bioprosthetic valve.But present bioprosthetic valve has influenced its wider application because too early calcification and regression makes its durability uncertain troubling again.Therefore, people crave for a kind of effective ways that can delay the calcification and the regression of bioprosthetic valve organization material always, and this is present biovalve research and improved focus.At the problems referred to above of prior art, the invention provides and a kind ofly the artificial bio-prosthetic valve membrane material is carried out modification handle delaying the new method of its calcification and regression, and the biovalve that adopts this method modification to handle.Compare with the artificial bio-prosthetic valve of prior art, the bioprosthetic valve of modification of the present invention can significantly reduce the calcification and the regression of organization material, thereby prolongs greatly service life.
Summary of the invention
The basic feature of bioprosthetic valve tissue (bovine pericardium or porcine aortic valve) structure is by the collagen fiber webbed skeleton that interweaves, and is filled by multiple mucopolysaccharide matrix therebetween.The most basic structural units of bioprosthetic valve material is the precollagenous fibers molecule, and degree that they are crosslinked and crosslinked quality have determined the stability and the fatigue durability of tissue.Generally to organize hot shrinkage temperature to weigh the crosslinking degree of tissue, what is called organizes hot shrinkage temperature to be meant in the aqueous medium of organization material below 40 degree in this area, when spending/temperature of aqueous medium when minute even rising water temperature causes the material structure shrinkage with 2.Its hot shrinkage temperature of natural biological lobe tissue (bovine pericardium valve or porcine aortic valve) that does not add processing is the 65-68 degree, and at first with the first generation bioprosthetic valve of formaldehyde treated (nineteen sixty-five-1969 year), its hot shrinkage temperature is the 74-76 degree, and serviceability rate only was 30% in 4 years; The second filial generation is with the bioprosthetic valve tissue of glutaraldehyde (Carpentier ' method) modification, and its hot shrinkage temperature is brought up to the 84-86 degree, and durability is enhanced about more than once.Used artificial biological heart valve still is heteroplasm's lobe (bovine pericardium valve or porcine aortic valve) of glutaraldehyde modification on the foreign market at present.Its 10 years serviceability rates are that 70%, ten five year serviceability rate is 30-40%[4].In decades, with regard to how reducing the calcification after bioprosthetic valve is implanted, having carried out a large amount of research its service life with further prolongation, but still having failed so far to find than the better chemical modification method of glutaraldehyde modification.
The present invention starts with from the characteristics of bioprosthetic valve tissue element structure, changes in the past chemical modification only based on the pattern of crosslinked amino, has successfully set up the crosslinked chemical modification new method of using on coordination compound and the valvular tissue collagen molecules of free carboxy.Organize hot shrinkage temperature can reach more than 100 degree through the bioprosthetic valve after this method modification, its structure stability significantly improves.Has extraordinary calcification effect simultaneously.
1. as the coordination compound of cross-linking agent
The crosslinked of bioprosthetic valve tissue can be strengthened structure stability effectively, thereby improves its durability, and this has become numerous scholars' common recognition.The nineteen sixty-eight famous scholar Carpentier of France is multiplied its durability, and uses till today always with the crosslinked bioprosthetic valve tissue of glutaraldehyde (GA).The principle of glutaraldehyde modification technology is the aldehyde radical by glutaraldehyde molecule two ends, make that the free amine group on the collagen molecules is cross-linked with each other in the valvular tissue, increase the crosslinking degree between the fundamental structural unit in the bioprosthetic valve tissue like this, thereby increased the stability of tissue.Yet great deal of research results shows that fatal weakness of the lobe leaf texture of GA modification is easy calcification, and the durable degree that its crosslinked action can reach biovalve has arrived the limit [5].For this reason, if will further improve its durability, need a kind of new cross-linking agent and new crosslinking method.
As the coordination compound of cross-linking agent be meant some metal transfer element such as aluminum (Al), chromium (Cr), ferrum (Fe) etc. in aqueous solution because hydrolysis is many exists with complex form, steric configuration is a regular octahedron, and they can be used for crosslinked biovalve tissue.With hydroxyl chromium is example, and its ligancy is 6, and space structure is a regular octahedron, can be expressed as (Cr (H in pure water
2O)
6).In solution, exist with hydroxyl chromium form because hydrolysis is many, except that hydrone, many aniones can be used as the ligand of chromium complex ion under different conditions, and different complexing powers is arranged.Replace rule according to interior ligand, the ligand that mating capability is bigger can enter replacement mating capability less ligand in boundary's in the coordination compound.Its mating capability of free carboxy on the collagen molecules is far longer than hydrone, and therefore, hydroxyl chromium can form crosslinked with the collagen protein combination.Simultaneously, hydroxyl oxygen wherein forms coordinate bond because of having more than a pair of not share electron pair so it can combine with another center chromium ion, forms the multinuclear hydroxyl chromium that contains two above chromium atoms.Thus, can increase or reduce the number of OH by the degree of hydrolysis that changes hydroxyl chromium, thereby can change the self-polymerization of its molecule.
Coordination compound generally provides with the saline solution form of above-mentioned metallic element.As when using the coordination compound of aluminum, various inorganic salt example hydrochloric acid salt, sulfate and the nitrate etc. that can get aluminum are mixed with aqueous solution, in case of necessity, add alkali in aqueous solution, are beneficial to the formation of coordination compound.Described alkali can be the alkali of alkali metal or alkaline-earth metal, as sodium hydroxide, potassium hydroxide, magnesium hydroxide or calcium hydroxide, preferably uses sodium hydroxide.The concentration of metal ion can be from 0.001mol/L to 1mol/L in the coordination compound aqueous solution, and concrete concentration those skilled in the art need not too much experiment and can determine after considering factors such as pending organization material size, thickness.The coordination compound solution of preparation has the certain absorption collection of illustrative plates, and the absorption collection of illustrative plates of iron carbonyl and hydroxyl chromium solution is seen Fig. 7 and Fig. 8.
Simultaneously, because coordination compound is to exist with the micromolecule state, thereby be easier to uniform distribution in tissue quickly than glutaraldehyde.This also helps with coordination compound tissue being carried out crosslinking Treatment.
The inventor finds that coordination compound is compared with glutaraldehyde method the crosslinking Treatment of organization material, has following characteristics: 1. crosslinked target group is a carboxyl, rather than amino.Because its number is amino three times, and is in free state fully, on distributing, order also has tangible stability advantage, and therefore, higher to the crosslinking degree of tissue.Simultaneously, be the poly-dot of valvular calcification owing to organize carboxyl (Dan Baijutang in tissue collagen albumen and the substrate all contains a large amount of carboxyls), crosslinked result is that a large amount of poly-dots is closed, and therefore has very definite calcification effect.And glutaraldehyde nonreactive calcification.Change by degree of hydrolysis when 3. hydroxyl chromium (HC) is crosslinked can make himself polymerization, so by changing its bulk of molecule and steric configuration, it is crosslinked to form multiple spot on three dimensions.And glutaraldehyde self almost is constant 5 carbochains, just 2 connections of linear " handing in hand ".4. hydroxyl chromium crosslinked with collagen not only, also crosslinked substrate (PG).And a glutaraldehyde crosslinked with collagen does not then have crosslinked action to substrate.5. because the molecule of hydroxyl chromium is adjustable, its micromolecule state distributes fast in tissue and evenly (only needs 1.5 hours), so working concentration is lower.And glutaraldehyde distributes slow (needing 48 hours), the working concentration height.In addition, the calcification effect of hydroxyl chromium also is different from the simple sealing carboxyl of indication on the general calcification meaning, and known all calcification methods at present all do not have tangible crosslinked action.
2. tissue material utilized in surgical implantation:
Mainly refer to flesh tissue materials such as bovine pericardium, porcine aortic valve, pig dorsal peritoneum, people's fascia lata and cerebral dura mater.Generally, in use, behind the material of waiting to obtain to exsomatize, prune away and remove unnecessary fat and no part, rinsing repeatedly in cold saline, see no color to naked eyes till.Then can be in compatible solution of physiology such as Hank ' s liquid soaked overnight, with further rinsing organization material, the ratio of solution and organization material can be 50: 1 to 2: 1, preferred 20: 1 to 3: 1, more preferably 10: 1 to 5: 1.Can change rinsing liquid in the rinse cycle, change once in general per 2 hours, the replacing primary effect was better in per 1 hour.
Organization material has been removed undesirable blood and tissue fluid wherein substantially through behind the above handling procedure, can be used for further crosslinking Treatment.
3. coordination compound is crosslinked
Coordination compound is to the crosslinked following steps that generally comprise of organization material:
A) pretreatment.Generally be to soak organization material, can contain sodium chloride in the formic acid solution, can stir frequently in the immersion process, or place under the oscillating condition with formic acid solution.Pretreatment can at room temperature be carried out, better effects if under 30 ℃ of temperature.
B) coordination compound is crosslinked.Place the coordination compound solution for preparing in advance to soak pretreated organization material, carry out crosslinking Treatment, processing procedure is carried out under oscillating condition.Processing can at room temperature be carried out, or it is ℃ better to 40 ℃ of effects to improve treatment temperature to 30.Can the pH value of solution progressively be improved with the pH value of alkali regulator solution in processing procedure, cross-linking effect be better like this.
C) post processing.To continue through the organization material of above-mentioned crosslinking Treatment to be soaked in a period of time in the treatment fluid, as 1 hour to 10 hours, the best be 2 hours, transferred to then in the acid sodium solution such as sulfurizing such as grade that contains 4% formaldehyde and preserved.Deng oozing Na
2SO
4Solution helps keeping the stable of cross-linked state as the coordination compound of cross-linking agent in solution.
4. the composite crosslinking of organization material is handled.
So-called composite crosslinking is meant organization material is pre-fixed with glutaraldehyde earlier, and then use the coordination compound crosslinking Treatment, the modification organization material of Huo Deing like this, wherein amino by glutaraldehyde cross-linking together, and carboxyl is crosslinked together by coordination compound, therefore its crosslinking degree is higher, and calcification and fatigue durability are better.
The processing of glutaraldehyde specifically can be referring to [6-8] substantially with the method for prior art.
5. modification organization material of the present invention
Can comprise flesh tissue materials such as bovine pericardium, porcine aorta and valve, pig dorsal peritoneum, people's fascia lata and cerebral dura mater with the organization material that coordination compound cross-linking treatment method of the present invention is handled.And the terylene artificial blood vessel of the artificial material of collagenic coating such as collagenic coating etc. also can use method of the present invention to handle, and improves its fatigue durability and calcification performance.
The inventor finds, organization material through coordination compound crosslinking Treatment of the present invention is compared with the organization material that the glutaraldehyde modification of prior art is handled, have following characteristics: the group that 1. is crosslinked is the carboxyl in the tissue, because carboxyl-content height in the tissue, be the poly-dot of valvular calcification simultaneously, therefore, crosslinked organization material crosslinking degree of the present invention is higher, and has clear and definite calcification effect simultaneously.The inventor adopts this area mensuration to organize the Bowes method of carboxyl-content that the carboxyl-content of organizing is after treatment measured, and the result shows that carboxyl-content is minimum in the crosslinked organization material of the present invention.2. coordination compound can be crosslinked with periplast, further like this increased the crosslinking degree in the organization material, therefore, strengthened the intensity and the stability of organization material.3. the same material that its hot shrinkage temperature of crosslinked organization material of the present invention is handled than the glutaraldehyde modification wants high, generally is not less than 90 ℃, and its hot shrinkage temperature of material that general glutaraldehyde modification is handled is about 85 ℃.Its hot shrinkage temperature of organization material of handling through composite crosslinking of the present invention generally is not less than 95 ℃.
Description of drawings
Fig. 1 is glutaraldehyde modification bovine pericardial tissue collagen fiber longitudinal sections, the visible more higher granule of electron density.
Fig. 2 is glutaraldehyde modification bovine pericardial tissue collagen fiber transverse section, the visible more higher granule of electron density.
Fig. 3 is an iron carbonyl modification bovine pericardial tissue transmission electron microscope photo, and tissue slice is the longitudinal section of collagen fiber, and whole visual field is not seen the Dan Baijutang granule that electron density is higher.
Fig. 4 is an iron carbonyl modification bovine pericardial tissue transmission electron microscope photo, and tissue slice is the cross section of collagen fiber, and whole visual field is not seen the Dan Baijutang granule that electron density is higher.
Fig. 5 is a hydroxyl chromium modification bovine pericardial tissue transmission electron microscope photo, and tissue slice is the longitudinal section of collagen fiber, and whole visual field is not seen the Dan Baijutang granule that electron density is higher.
Fig. 6 is a hydroxyl chromium modification bovine pericardial tissue transmission electron microscope photo, and tissue slice is the cross section of collagen fiber, and whole visual field is not seen the Dan Baijutang granule that electron density is higher.
Fig. 7 is the absorption collection of illustrative plates of iron carbonyl solution.
Fig. 8 is the absorption collection of illustrative plates of hydroxyl chromium solution.
The specific embodiment
1. coordination compound is to the crosslinking Treatment of organization material
1). the preparation of coordination compound solution: get analytically pure AlCl
36H
2O and NaOH solid add water and are mixed with a series of Al
3+Ion concentration is respectively 0.0300,0.0500 and 0.100mol/dm3, and OH/Al is than the hydroxy Al solution for standby that is respectively 0,1.0,1.5,2.0 and 2.5.
2) preparation of organization material: get the fresh bovine pericardium, prune away after exsomatizing and remove unnecessary fat and no part, rinsing to naked eyes are seen till the no color in cold saline.Clean environment in Hank ' s liquid soaked overnight (tissue and flowing fluid ratio are 1: 5-10), each hour changed liquid once.
3) coordination compound crosslinking Treatment:
A) pretreatment: ready bovine pericardium is cut into 6～8 * 10～12cm with blade
2Size places the formic acid solution (pH 2.5) that contains 0.9%NaCl, and 30 ℃ of water-baths were vibrated 30 minutes.
B) coordination compound is crosslinked: pretreated organization material is placed 0.0625mol/dm3, and OH/Al is in 0.5 the hydroxy Al solution, 32 ℃ of water-baths vibrations 3.5 hours; The pH of test material treatment fluid also uses 10%NaHCO
3Improve 0.4pH unit, and then 36 ℃ of water-bath vibrations 45 minutes; Measure the pH of material processed liquid again, and use 10%NaHCO
3Improve 0.4pH unit, 36 ℃ of water-baths were vibrated 45 minutes; Continue to use 10%NaHCO
3Regulator solution pH value to 4.0,40 ℃ of water-baths were vibrated 1.5 hours.
C) post processing: the organization material after crosslinked was continued to be soaked in the treatment fluid 2 hours, place the grade that contains 4% formaldehyde to ooze Na then
2SO
4Preserve standby in the solution.
2. glutaraldehyde and coordination compound are handled the composite crosslinking of organization material
Promptly before organization material being carried out crosslinking Treatment with coordination compound, handle earlier, like this its intensity of crosslinked organization material of Huo Deing and the calcification performance same material that all is better than only using the coordination compound crosslinking Treatment with the glutaraldehyde (concentration is 0.25-0.3%) of low concentration.
It still is example with the bovine pericardium.Choose ready bovine pericardial tissue material, being cut into size is 6～8 * 10～12cm
2Flaky material, soaked 48 hours with the 0.05mol/L HEPES buffer (pH7.4) that contains 0.25% glutaraldehyde, place 0.05mol/LHEPES buffer (pH7.4) preservation that contains 0.3% glutaraldehyde standby again.
3. crosslinked organization material of the present invention
To contrast through the bovine pericardial material of said method crosslinking Treatment and the bovine pericardial material and the undressed bovine pericardial material of prior art, the result is as follows:
(1). crosslinked group
Among the present invention, organize carboxyl to be crosslinked in the bovine pericardial material of crosslinking Treatment, this is by measuring as can be seen the carboxyl-content in the organization material after handling.
With the fresh bovine pericardial tissue is contrast, makes to organize carboxyl-content mensuration [6] with the bovine pericardial material tissue that Bowes method [9,10] is handled GA and coordination compound is handled after (hydroxy Al and hydroxyl chromium).To organize carboxyl-content be 0.7 ± 0.016mmol/g to matched group as a result; The GA group is 0.88 ± 0.012mmol/g; Complex composition is not: hydroxy Al is 0.36 ± 0.012mmol/g, and hydroxyl chromium is 0.34 ± 0.014mmol/g, is starkly lower than GA group (P＜0.001).
(2). periplast is crosslinked
(Proteoglycan PG) is the main component of biological tissue's substrate to Dan Baijutang, and ammoniated ruthenium oxychloride is the polycation structure, and very easily the Dan Baijutang with the polyanion structure combines.Under transmission electron microscope, can make these Dan Baijutang granules present the higher granule of electron density.Therefore, but adopt ammoniated ruthenium oxychloride group Electronic Speculum specificity to show PG granule [7].We handle by scanning electron microscope and transmission electron microscope observing GA with the dyeing of ammoniated ruthenium oxychloride group and coordination compound processing (hydroxy Al and hydroxyl chromium) after the bovine pericardial material tissue, the results are shown in Figure 1-6.The result shows that the bovine pericardial tissue PG granule after coordination compound is handled (hydroxy Al and hydroxyl chromium) obviously reduces.
(3). the calcification performance
Bovine pericardium limb that hydroxyl chromium (HC) is handled and GA modification bovine pericardium limb were implanted subcutaneous rat after 21,60,90 and 120 days respectively, measured with atomic absorption method [11,12] tissue calcium content.The result is as shown in table 1 below.
Table 1.HC and GA modification bovine pericardium limb are implanted 21,60,90,120 days calcium contents (μ g/mg) of Wistar subcutaneous rat
| Valve | Calcium content | |||
| 21 days | 60 days | 90 | 120 days | |
| HC (0.1%) modification | ?1.5±0.21 | ?1.68±0.24 | ?4.67±2.65 | ?5.93±2.47 |
| GA (0.3%) modification | ?125.0±13.14 | ?200.8±21.09 | ?230.5±0.21 | ?245.56±10.07 |
| ?n | ?14 | ?14 | ?12 | ?13 |
The bovine pericardium limb implantation dog cyclic system that coordination compound is handled has obtained calcification effect preferably equally.
List of references:
1. Zhu Xiaodong, Xue Ganxing, " department of cardiac surgery guide ", world book publishing company, October nineteen ninety, front page, the 389th page
2.Edwards?Lifesciences.News.http：//www.edwards.com.Aug.，312000
3. rich vivid, Huang Zhendong, Cen Run are superfine, the popular present situation of China's rheumatic heart disease, Chinese cardiovascular diseases's magazine, April in 1998 the 26th volume the 2nd phase 98-100 page or leaf
4.Ham-mermeiater?KE.A?comparison?of?outcomes?in?men?11?yearsafter?heart?valve?replacement?with?a?mechanicalvalve?orbioprosfjesis.NEng?J?Med，1993，328：1289-1296
5.Magilligan?DJ.The?future?of?bioprosthetic?valves?Trans?Am?SocArtif?Intern?Organs?1988，34：1032
6.Carpentier?A.et?al.Six-year?follow-up?of?glutaraldehyde?preservedheterografts：With?particular?reference?to?the?treatment?of?congenital?valvemolformation.J?thorac?Cardiovasc?Surg?1974，68：771
7.Carpentier?A.el?al.Continuing?improvements?in?valvularbioprostheses.J?Thorac?Cardiovasc?Surg?1982，83：27
8.Carpentier?A.et?al.Techniques?for?prevention?of?calcification?ofvalvular?bioprostheses.Circ?1984，70(Suppl?I)：165
9.Bowes?JH，et?al.The?amino-acid?composition?and?titration?curve?ofcollagen.Biochem.J，1948，43：358
10. Yi Dinghua, Liu Weiyong, Wang Baiyun etc. alleviate the experimentation of xenogenesis (pig) aortic valve calcification, Chinese cardiovascular thoracic surgery magazine, and volume was the 48th page in 1988 years the 4th
11.Levy，R.J.et?al.，Vitamin?K-dependent?calcium?binding?proteins?inaortic?valve?calcification.J.Clin.Invest.，1980，65：563
12. geologic chemistry canonical reference sample seminar, the development of geologic chemistry canonical reference and analytical method GSD1-8, Geology Publishing House, Beijing,, the 182nd page in 1986
Claims (12)
1. a method that improves biological organization material endurance and calcification performance is characterized in that, after the use formic acid solution was handled biological organization material, the solution of the coordination compound of reuse transition metal was handled biological organization material.
2. the method for claim 1, this method comprise that also the biological organization material that the coordination compound solution of transition metal was handled continues to soak 1-10 hour in coordination compound solution, transfer to then to contain waiting in the sulfurizing acid sodium solution of formaldehyde and preserve.
3. the method for claim 1 is characterized in that using containing 0.9% sodium chloride, and pH value is that 2.5 formic acid solution is at 30 ℃ of following oscillation treatment biological organization materials.
4. the method for claim 3 is characterized in that using coordination compound solution oscillation treatment biological organization material under 30 ℃-40 ℃ temperature, and adds alkali in processing procedure the pH value of solution is progressively raise, and finally reaching pH value is 4.
5. the method for claim 4, wherein said biological organization material is the artificial material of flesh tissue material or collagenic coating, or the above-mentioned biological organization material of handling through glutaraldehyde solution, wherein said flesh tissue material is selected from bovine pericardium, porcine aorta and valve, pig dorsal peritoneum, people's fascia lata and cerebral dura mater.
6. the method for claim 5, wherein said biological organization material is a bovine pericardium.
7. the process of claim 1 wherein that transition metal is chromium, aluminum or ferrum, in the saline solution of transition metal, add sodium hydroxide, form the coordination compound solution of transition metal.
8. the method for claim 8, wherein transition metal is a ferrum.
9. the method for claim 8, wherein transition metal is a chromium.
10. claim 1-4 or 7 each methods is characterized in that adopting glutaraldehyde that biological organization material is carried out pretreatment using before coordination compound solution handles biological organization material.
11. the method for claim 10, wherein glutaraldehyde concentration is 0.25-0.3%.
12. use the biological organization material of the method preparation of claim 10, wherein the carboxyl of the carboxyl in the organization material and periplast's molecule all is crosslinked.
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|---|---|---|---|
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| AU2014215646B2 (en) * | 2013-02-06 | 2017-10-19 | Lifecell Corporation | Methods for localized modification of tissue products |
| CN105326581B (en) * | 2015-09-29 | 2017-12-26 | 中国科学院金属研究所 | A kind of method for preparing polyethylene glycol protein fiber composite heart valve prosthesis |
| CN117563049A (en) * | 2024-01-15 | 2024-02-20 | 北京佰仁医疗科技股份有限公司 | Ophthalmic biological patch for posterior scleral reinforcement and preparation thereof |
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