胶原基生物膜的制备及性能研究
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摘要
胶原是最丰富的哺乳动物蛋白质,约占体内蛋白质的20%~30%,是皮肤、软骨、动脉血管壁及结缔组织的主要成分,在动物体内起支持、保护、连接等多种作用。可制成不同形式的材料,如膜、海绵、带、薄片等。成胶材料应用于血管和伤口敷料、皮肤缺陷的弥补中。这些基质可帮助受损组织的重建。除了在生物学上的相适性外,这些材料的物理特性也与被取代的组织基本相似。
     明胶是胶原降解的产物,胶原是明胶的前身,降解后的明胶仍然保持着胶原的某些构象与属性。主要由20种氨基酸所组成,其中甘氨酸占三分之一,脯氨酸与羟基脯氨酸之和占三分之一,主要组分为α_1、α_2、β以及γ三联体,微黄色,易溶于水,随温度升高或降低有溶胶与凝胶的可逆转化的优良特性,干燥后的明胶涂层呈透明状、具有一定的机械强度,在感光工业、医药工业、食品工业以及其他工业中获得非常广泛的应用。
     本论文选用γ-(2,3-环氧丙氧)丙基三甲氧基硅烷(KH-560)作为交联剂对明胶膜进行交联。KH-560主要用来改善有机材料与无机材料表面的粘接性能,可提高制品的机械以及力学性能。
     本论文我们还采用聚乙二醇、壳聚糖以及聚乙烯醇分别对明胶/KH-560复合膜进行改性。聚乙二醇为乙二醇与环氧乙烷的缩合物,在各种混合物中作为增湿剂来吸收和保持水分,还可用作薄膜的增塑润湿剂,可增强薄膜的强度和尺寸稳定性。壳聚糖是自然界中唯一的碱性多糖,在体内可以降解,无生物毒性及排斥反应,有很好的成形性及操作性。壳聚糖分子中含有大量的氨基,可形成Sehif碱式凝胶。聚乙烯醇是水溶性高分子聚合物,无毒,生物相容性好,可生物降解。这些材料均可明显改善明胶膜的力学性能和溶胀性能等,可望用于稳定性差的生物活性物质的包覆和作为其载体。随着组织工程的发展,无抗原性的壳聚糖与聚乙烯醇等共混物将在细胞培养、细胞外基质、骨架及生物活性物质的释放等众多方面得到应用,日益显示其在生物医学材料领域的重要性。
     本文对复合膜的脆性、透光度、膨胀度、抗张强度、断裂伸长率等性能进行了表征。结果表明,聚乙二醇的使用可在一定程度上提高明胶/KH-560膜的机械性能。壳聚糖的加入引入大量的氨基、羟基和-C-O-C-基团,可与明胶的羧基反应,大大提高明胶/KH-560膜的机械性能,但是成膜后的透光度较差。聚乙烯醇不但可以提高复合膜的透明度,而且大大提高明胶/KH-560复合膜的最大负荷、断裂点负荷、伸长率、膨胀性能等。
Collagen is the most abundant mammal protein, nearly about 20%~30% in the body. It is the basis component of the skin, cartilage, artery afferent wall and knot organization, there are various function in the animal body, such as support and protection, conjunction…etc. Besides, it also can be made into the material of different form, like memrane, sponge, cingulum, thin slice etc.. The membrane can be applied into parenchyma aggrandize, blood vessel and wound dressing, skin disfigurement recuperate. Except the biologically suitability, this material can help the reconstruct of damage tissue, and its physics characteristic is also similar with the substitutional tissue.
     Glutin is the outcome that the collagen disorganization, some of its contracture and property was similar with collagen. It’s composed with 20 kinds of amino acidses, among them, 1/3 was glycin, 1/3 was proline and hydroproline. Mostly element wasα_1,α_2,βandγcomplement, who easily dissolved in water, having the good characteristic that dissolved gum and gel can conver to each other along with the tempreture going up or lower, drily, presents a transparent form and has certain machine strength, acquire a very extensive application in exposed to light industry, the medicine industry, the food industry and other industry.
     This thesis chooses KH-560 as to act with glutin. It is mainly used to improve organic and inorganic materials surface connect function and, can raise machine and mechanics function of ware. This thesis we still adopt Polyglycol, Chitosan and Polyvinyl alcohol to change the properties of menbrane which compounded by glutin and KH-560.Polyglycol is the polymer of glycol and ethane, is used to increase humidity and absorb moisture and to strengthen the membranes intensity and stability. The chitosan is the only alkaline amylose in the nature, can decline in the body, have good biocompatibility, low toxicity, high mechanical strength and good film-forming ability. There are many amido in the chitosan member, can fome Sehif alkali gelatin. PVA is the water solubility macromolecule polymer, which is innoxious and has a good biological adaption. These materials all can obviously improve the mechanics and dissolve property of glutine membranes. They can be made into cover materials and as the carrier of some less stability products. Along with the development of organization engineering, the polysaccharide and PVA will be used in many areas, such as cell incubate, framewoke and biological materials release, for its unantigentic,
     In this paper, transport ratio, tensile strength, rupture elongation ratio were determined. The results indicated that the polyglycol can increase mechanical properties of. the membranes. Chitosan can enhance mechanical properties greatly, but the membranes transport ratio is lowest. The amido, hydroxide, and–C-O-C- groups in chitosan can act with carboxyl in glutin. PVA can enhance the membranes taansport ratio, and the other mechanical properties, such as peak load, breakpoint load, elongate rate, distensibility all are most.
引文
[1] Harkness R D.Biological functions of collagen[J]. Biology. 1961, 36:399-463
    [2] Lee C H, Singla A, Lee Y Y, Biomedical applications of collagen[J]. International J -ournal of Pharmac eutics 2001, 221:1-22
    [3] Reich G.Collagen report: a review about the present state. Lether. 1995. 46(R):192- 199
    [4] 阎隆飞,孙之荣.蛋白质分子结构[M].北京:清华大学出版社,1999
    [5] 林炜,穆畅道,王坤余等.皮革固体废弃物资源化(Ⅱ)胶原的性质及其在医药和化妆品工业中的应用[J].中国皮革,2001,30(15):8-11
    [6] 但卫华,王坤余等,胶原的医学应用及其发展前景[J].生物医学工程与临床2004,8(1):47-48
    [7] Yannas IV.Tissue regeneration by use of collagen–glycosaminoglycan copolymers [J]. Clin Mater 1992, 9:87-179
    [8] Miyata T, Taira T, Noishiki Y. Collagen engineering for biomaterials use[J]. Clin Mater 1992,9: 48-139
    [9] Gorham SD,Srivastava S,French DA, Scott R.The effect of gammaray and ethylene oxide sterilization on collagen-basedwound-repair materials[J]. Mater Sci Mater Med 1993, 4: 9-40
    [10] De Vries HJC, Zeeglar JE, MiddlekoopE, Gijsbers G, vanMarle J,Wildevuur CHR, Westerhof W.Reduced wound contraction and scar formation on punch wounds[J] Native collagen dermal substitutes. A clinical study. Br J Dermatol 1995,132:7-690
    [11] Silver FH, Wound dressings and skin replacement. In: Silver FH, editor. Biomateri -als medical devices and tissue engineering-an integral approach[J]. London: Chap -man & Hall, 1994. p. 46-91
    [12] van Luyn MJA, van Wachem PB, Dijkstra PJ, Olde Damink LHH, Feijen J. Calcif -ication of subcutaneously implanted collagen in relation to cytotoxicity, cellular interactions and crosslinking[J]. Mater Sci Mater Med 1995;6:288-96
    [13] Miller EJ, Rhodes RK. Preparation and characterization of the different types of collagen[J]. Meth Enzymol 1982:82:A:33-64
    [14] Rajaram A, Chu CC. GTA in collagen gel formation[J]. Biomater Sci Polym Ed 1990;1:167-72
    [15] Chvapil M, Holubec H, Chvapil T. Inert wound dressing is not desirable[J]. Surg Res 1991;51:245-52
    [16] Schroeder-Tefft, Bentz H, Estridge TD. Collagen and heparin matrices for growth factor delivery[J]. Control Release 1997;48:29-33
    [17] Charulatha V, Rajaram A. Crosslinking density and resorption of dimethyl suberim -idate treated collagen[J]. Biomed Mater Res1997;36:478-86
    [18] Charulatha V, Rajaram A. Dimethyl 3,30-dithiobispropionimidate: a novel cross lin -king reagent for collagen[J]. Biomed Mater Res 2001;54:122-8
    [19] Nimni HE, Cheung DT, Strates R, Kodama M, Sheik K.Bioprosthesis derived from crosslinked and chemically modifiedcollagenous tissues. In: Nimni ME[J], editor. Collagen, vol. III.Boca Raton, FL: CRC Press, 1988: 1-38
    [20] Kato YP, Silver FH. Formation of continuous collagen fibres: evaluation of biocom -patibility and mechanical properties[J]. Biomaterials1990;11:169-75
    [21] Wasserman AJ, Kato YP, Christiansen D, Dunn MG, Silver FH. Achilles tendon replacement by a collagen fiber prosthesis: morphological evaluation of neotendon formation[J]. Scann Microsc1989;3:1183-200
    [22] Cavallaro JF, KempPD, Ktaus KH. Collagen fabrics as biomaterials[J]. Biotech Bioeng 1994;43:781-91
    [23] Weadock KS, Miller EJ, Bellincampi LD, Zawadsky JP, Dunn MG. Physical cros -slinking of collagen fibres:comparison of ultraviolet radiation and dehydrotherma -thermal treatment[J]. Biomed Mater Res 1995,29:1373-9
    [24] Flory PJ, Rehner Jr J. Statistical mechanics of crosslinked polymer networks II. Swelling[J]. Chem Phys 1943,11:521-6
    [25] 李志强.生皮蛋白质化学基础[M].成都:成都科技大学出版社,1988
    [26] 曹正国,李成章.常用蛋白质交联方法及其对胶原的影响[J].国外医学生物医学工程分册.2001,24(4):187-191
    [27] 石碧,狄莹.植物多酚[M].北京:科学出版社,2000,161-163
    [28] Hirono I.Naturally occurring carcinogens of plant origin[J].Elsevier,Amsterda, 1987:161-162
    [29] Alkira N,Takashi S.Uptake and recovery of gold by immobilized persimmom tannin[J]. Chem Tech Biotechnol 1993,57:321-326
    [30] 马志红,陆忠兵,石碧.单宁酸的化学性质及应用[J].天然产物研究与开发,2002,15(1):87-90
    [31] 张铭让,陈武勇.鞣制化学[M].北京:中国轻工业出版社,1999,8:132-133
    [32] 陈武勇,朱梅湘.皮胶原的提取及胶原生物膜材料的研究[J].中国皮革,2003,32(7):24-26
    [33] M cPherson JM ,L edger PW. The p reparation and physicochemical characterization O f an injectable form of reconst ituted, glutaraldehyde cro sslinked, bovine corium co llagen[J]. Journal ofB iomedicalM aterial Research. ,1986,20: 79-92
    [34] Olden Damink LHH, D ijk stra PJ , et. Crosslinkingof dermal sheep co llagen using hexamethlene diisocyanate[J]. M ater Sci: M ater M ed, 1995, 6:429-34
    [35] Naimark WA,Pereira CA,Tsang K,Lee JM.HMDC cro sslinking of bovine pericardi -al tissue: apotential role of the solvent environment in the design of biop ro sthet ic materials[J]. Material Sci MaterMed, 1995, 6: 235-41
    [36] NimniM E,Cheung D,St rates B,KodamaM , et.Chemically modified collagen: a na -ture biomaterial for tissue replacement[J]. Biomed Mater Res, 1987, 21: 741-771
    [37] Sung HW , Hsu HL et. Crosslinking characteristics of biological tissues fixed with monofunctional or multifunctional epoxycompounds[J]. Biomaterials, 1996, 17: 1405-1419
    [38] Tu R, Quijano RC et Apreliminary study of the fixation mechanism of collagen rea -ction with a polyepoxy fixative[J]. Int J Art if Organs. , 1993,16(7):537-44
    [39] Xi T , Liu F, Xi B. Effect of pret reatment with epoxy compounds on the mechanic -al properties of bovine pericardial bioprosthetic materials[J]. JB iomater App l. , 1992, 7 (1):61-75
    [40] Shen SH, Sung HW , Tu R, Hata C, L in D,Noishiki Y, Quijano RC.Characterizati -on of a polyepoxy compound fixed porcine heart valve bioprosthesis[J]. Appl Biomater. , 1994, 5 (2) :159-162
    [41] Sung HW , Shih JS, Hsu CS. Crosslinking characteristics of porcine tendons: effect -s of fixation with glutaraldehyde or epoxy[J]. Biomed Mater Res.1996, 30 (3):361 -367
    [42] Sung HW , Hsu CS, Lee YS, Lin DS.Crosslinking characteristics of an epoxyfixed porcine tendon: effects of pH,temperature and fixative concent ration[J]. Biomed MaterRes, 1996, 31(4): 511-518
    [43] 张雪燕,顾其胜.透明质酸与胶原蛋白复合材料的制备及其应用[J].上海生物医学工程杂志,2003,24(1):26-28
    [44] Nicolas FL , Gagnieu CH. Denatured thiolated collagen. I. Synthesis and characteri -zation[J]. Biomaterials,1997,18(11):807-813
    [45] Petite H, Frei V, Huc A, Herbage D. Use of diphenylpho sphorylazide for crosslink -ing collagen based biomaterials[J]. Biomed Mater Res., 1994, 28 (2):159-165
    [46] Thomas J.Koob etc Material p ropert ies of polymerized NDGA collagen composit -e fibers:development of biologically based tendon constructs[J]. Biomaterials, 2002, 23:203-212
    [47] Goycollea MV, Muchow DC, Scholz M.In search of collagen as eardrum graft supp -ort in dogs [J].Acta Otolaryngol,1989, 107(5): 450
    [48] 侯小平,萧轼之等.异种胶原生物膜鼓膜移植的生物相容性[J].山东医大基础医学院学报,2001,6,15(3):135-137
    [49] 王韦,孙家玲,刘俊龙等.可溶性胶原的制作与临床应用[J].生物医学工程学杂志,1988,5(4):224-225
    [50] Lamme EN,DeVries HJT,VanVeen H,et al.Extracellular matrix characterization du -ring healing of full-thickness wounds treated with a collagen elastin dermal sub -stitute shows improved skinregeneration in pigs[J]. Histochem, 1996, 44(11): 1311-1316
    [51] 杨珺,肖仕初等.海绵状胶原膜制备真皮支架及其生物活性研究[J].第二 军医大学学报,2002,4,23(4):437-438
    [52] 黄任远,胡云龙等.胶原蛋白膜改性技术.南京工业大学学报,2004,7,26(4):23-26
    [53] Chowdhury PS .Improving antibody affinity by mimicking somatic by permutatio -n in vitro[J], Nat Biotechnol,1999,17(6):568
    [54] Jackson H,Bacon L,Pedley RB,el.al,Antigen specificity and tumor targeting effici -ency of human carcinocmbryonic anti Cancer[J], Biotechnol, 1998, 78(2):.181- 184
    [55] 梁国栋.最新分子生物学实验技术[M],北京:科学出版社,2001,87-88
    [56] Rao K P,Alamelus S ,Effect of crosslinking agent on the release of an aqueous marker from lipromes sequestred in collagen and chitosangels[J]. Science, 1992.71.161
    [57] 崔新明, 崔丽等.复合生物膜的制备及扫描电镜观察[J].电子显微学报. 2003,22(6):661
    [58] Locci P , Calvitti M, Belcastro S , et al . Phenotype expression of gingival fibroblas -sts cultured on membranes used in guided tissue regeneration[J]. Periodontol , 1997,68 : 857-863
    [59] Schlegel AK, Busch F , Mehl A , et al . Preclinical and clinical studies of a collage -n membrane[J]. Bioma. terials, 1997 , 18 :535-538
    [60] 邹海波.胶原膜在引导性再生中的应用[J].北京生物医学工程,2003,6,22(2):151-154
    [61] Minabe M, Kodama T,Kogou T, et al . Different crosslinked types of collagen impl -anted in rat palatal gingival[J]. Periodontol,1989,60 :35-43
    [62] Kodama T , Minabe M, Hori T , et al . The effect of various concentrations of colla-gen barrier on periodontal wound healing[J]. Periodontol ,1989 , 60 : 205-210
    [63] Quteish D , Dolby AE. The use of irradiated2crosslinked human collagen membran -e in guided tissue regeneration[J]. Clin Periodontol,1992,19 : 476-484
    [64] Brunel G, Piantoni P , Elharar F , et al . Regeneration of rat calvarial defects using a bioabsorbable membrane technique : Influence of colla2gen cross2linking[J]. Periodontol,1996,67:1342-1348
    [65] Zahedi S , Legrand R , Brunel G, et al . Evaluation of a diphenylphosphorylazide crosslinked collagen membrane for guided bone regeneration in mandibular defects in rats[J]. Periodontol , 1998, 69: 1238-1246
    [66] Pitaru S , Noff M, Grosskopf A , et al . Heparan sulfate and fibronectin improve the capacity of collagen barriers to prevent apical migration of the junctional epithelium[J]. Periodontol,1991, 62: 598-601
    [67] Blumenthal NM, Steinberg J . The use of collagen membrane barriers in conjunctio -n with combined demineralized bone collagen gel implants inhuman infrabony defects[J]. Periodontol, 1990, 61: 319-327
    [68] Dowell P, al Arrayed F , Adam S , et al . A comparative clinical study : The use of human type ? collagen with and without the addition of metronidazole in the GTR method of treatment of periodontal disease[J].Clin Periodontol,1995,22:543-549
    [69] Chen CC,Wang HL,Smith F,et.al .Evaluation of a collagen membrane with and wi -thout bone grafts in treating periodontal intrabony defects[J]. Periodontol, 1995, 66:838-847
    [70] Hammerle CH,Karring T. Guided bone regeneration at oral implant sites[J]. Period -dontol, 1998 ,17 :151-175
    [71] IgIhaut J , Aukhil I , Simpson DM, et al . Progenitor cell kinetics during guided tiss -ue regeneration in experimental periododntal wounds[J]. Periodont Res, 1988, 23 :107-117
    [72] Colangelo P , Piattelli A , Barrucci S , et al . Bone regeneration guided by resorbabl -e collagen membranes in rabbits. A pilot study[J]. ImplantDent , 1993 , 2:101-105
    [73] Hürzeler MB , Kohal RJ , Naghshbandi J , et al . Evaluation of a new bioresorbable barrier to facilitate guided bone regeneration around exposed implant threads : An experimental study in the monkey[J]. Int J Oral Maxillofac Surg,1998 ,27 :315-320
    [74] Dongieux JW, Block MS , Morris G, et al . The effect of different membranes on onlay bone graft success in the dog mandible[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod,1998,145-151
    [75] Brunel G,Benque E,Frederic E, et.al.Guided bone regeneration for immediate nons-ubmerged implant placement using bioabsorbable materials in beagle dogs[J]. Clin Oral Implants Res,1998,9:303-313
    [76] 张永刚,卢世壁,王继芳等.降解材料隔膜引导性骨再生的实验研究[J].中 华创伤杂志,1999,15(1):5-8
    [77] Schreiner M.,Huyaskens-Keil S.,Krumbein A.,Prono-Widayat H.effect of film pack aging and surface coating on primary and secondary plant compounds in fruit and vegetable products[J].Jorunal of Food Engineering 2003,56:237-240
    [78] Thomazine Maira,Carvalho Rosemary A.,Sobral Paulo J.A.Physical properties of gelatin films plasticizen bu blends of glycerol and sorbitol[J].Journal of Food Sci -ence:Food Engineering and Physical Properties 2005,70(3):172-176
    [79] Yakimets Iryna,Wellner Nikalaus,Smith Andrew C.,et al.Mechanical properties with respect to water content of gelatin films in glassy state [J].Polymer 2005,46:12577-12585
    [80] Carvalho R.A.de, Grosso C.R.F.Characterization of gelatin based films modified with transglutanminase,glyoxal and formaldehyde [J].Foof Hydrocolloid, 2004, 18:717-726
    [81] Chiellini Emo,Cinelli Patrizia,Femandes Elizabeth Grillo,et al.Gelatin-based blends and composites.morphological and thermal mechanical characterization [J]. Bilmac -romolecules 2001, 2: 806-811
    [82] Kandil Sherif,Kenawy E1-Refaie,E1-Maghraby Azza.Recycling of pharmaceutical waste gelatin for congtrolled-release applications.I.A 2,4-dicholorphenoxy acetic acid based system[J].Journal of Applied Polymer Science 2004,91:2313-2319
    [83] 曹娜,符玉华,贺军辉.明胶膜作为可食性包装膜、覆盖膜及医学材料的应用.明胶科学与技术.2006,12,26(4):195-202
    [84] Andreas Bernkop·Schntlrch,Margit Hornof,Davide Guggi, Thiolated chitosans [J]. European Journal of Pharmaceutics and Biopharmaceuties,2004,57(1):9-17
    [85] Mojca Kerec,Marija Bogataj,Peter Veranic,et.a1.Permeability of pig urinary bladde -r wall:the efect of chitosan and the role of calcium[J].European Journal of Pharnac -e:utical Sciences,2005,25(1):113-121
    [86] WS Wan Ngab,A Kamari,Y J Koay,Equilibrium and kinetics studies of adsorption of copper(II)on chitosan and chitosan/PVA beads[J].International Journal of Biol -ogical Macroraolecules, 2004,34(3):155-161
    [87] Minghua Ho, Darning Wang,Hsyucjen Hsich,et.a1.Perparation and characterizeati -on of RGD immobilized chitosan scafolds[J]. Biomaterials.2005,26(16):3197-3206
    [88] 姚康德,尹玉姬,成国翔,等.壳聚糖基聚合物的生物医学研究进展[J].高技术通讯,1998,8(9):55-58

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