Characteristics of Hyaluronic Acid Derivative Cross-linked by Polyethylene Glycol Characteristics of Hyaluronic Acid Derivative Cross-linked by Polyethylene Glycol

Characteristics of Hyaluronic Acid Derivative Cross-linked by Polyethylene Glycol

  • 期刊名字:武汉理工大学学报英
  • 文件大小:581kb
  • 论文作者:CHEN Jinghua,FAN Donghui,XU Zh
  • 作者单位:College of Materials Science and Technology,College of Publishing and Printing,The Institute of Qisheng Biomaterial Tech
  • 更新时间:2020-12-22
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Vol.20 Suppl.Journal of Wuhan University of Technology - Mater. Sci. Ed.Dec.2005Characteristics of Hyaluronic Acid Derivative Cross-linkedby Polyethylene Glycol*CHEN Jinghua',2 FAN Donghui' XU Zheng° GU Qisheng'(1. College of Materials Science and Technology, Tongji University, Shanghai 200092, China;2. College of Publishing and Printing, University of Shanghai for Science and Technology , Shanghai 200093 , China;3.The Institute of Qisheng Biomaterial Technology, Shanghai 201106, China)Abstract: Characeristic and dynamic rscosities of Hyaluronic acid ( HA) drirative modified by polyeth-ylene glycol ( PEG) uere tested with diferent reaction times (6 h,12 h,18 h and 24 h), djferent molar ratioof HAI PEG (1/10,1/5,1/3 and 1/2), diferent molecular weight of PEG(400,6 000 and 20 000) and massfraction is 0.4% by Wushi Viscosimeter and L-90 Rheomneter at 25 C . Characeristic riscosity of HA driatirehad the largest volue in 12 h, which dereased with increasing of PEG molecular weight, but is aqueous dynam-ic tscosity increased with increment of PEC molecular weight . Meanwhile ,we tested dynamic mechanic propetiesof HA deivntive by 3ARES3 Rheometer at 25 C to study uscelasic changes and to compare change diferenefrom viscosity to elasticit with the changes of vibration frequency betueen umodifed HA and HA derivative.Change from low vibrated frequency to high one of solution rsulted in change from riscosity 1o elasicity of solu-ion. In conclusion, as to the rheological properties,structure modified HA derivutive meets the requirement of bi-omaterial .Key words: hyaluronic acid; charoateristic tiscosity; dynamical riscosity; rscelastic charateris-tics1 Introductionylene glycol was proved in terms of its rheological proper-ties in medical field.Hyaluronic acid (HA) is a glycosaminoglycan com-2 Experimentalposed of repeating disaccharide units of glucuronic acidand glucosamine residues , which is abundant in the extra-2.1 Materialscellular matrix, vitreous body and synovial fluid. Its vis-HA derivative cross-linked by polyethylene glycolcoelastic and biocompatible properties makes it a useful( PEG) was obtained in our lab4l.tool for medical applications' 2. But natural HA is solu-2.2 Characteristic viscosity testingble in water and is not resistant to enzymatic degradation,HA derivative characteristic viscosities were testedthus hindering its wider application as a type of biomedi-cal materials. In recent years, it is more desired for HAby Wushi Viscousmeter at 25 9C under different reactionto maintain suitable retention time in vixo, especiallytimes , different PEG Mu and different molar ratio of HA/when preventing conglutination and flling parenchyma, orPEG with. Firstly, characterstic viscosities of HA deriva-even to be kept long-time existing. All of which inspiredtive were tested under diferent reaction times of 6 h,12 .investigators great interest to change natural HA structureh,18 h and 24 h, with PEG Mw 6 000 and HA/PEG mo-and make even more detailed research works. Structure-lar ratio 1/10. Secondly, it was tested under reaction timechanged HA derivatives retain equal fine biocompatibili-of 18 h and with HA/PEC molar ratio 1/10, and PEG Mwties and better rheological properties of natural HA. Norespectively was taken as 400, 6 000 and 20 000. At last,it was tested under reaction time of 18 h and with differenttoxicity and no stimulative to human being body3J .In this thesis, HA derivative, modifed by polyethyI-HA/PEG molar ratio 1/10, 1/5, 1/3, 1/2 (PEG Mw 6ene glycol (PEG),was tested and analyzed for its rheo-logical properties. Based on all the above analyses, the2.3 Dynamic viscosity testingapplication feasibility of HA derivale modified by polyeth-Testing was carried on by L90 Rheometer at 25 Cwith solution mass fraction was 0. 4%,Firstly, dynamic(Received:Feb. 24,2004;Acepte: May 23,2005)viscol中国煤化工:asured with diferentCHEN Jinghua(陈景华): Assoc. Prof.; Ph D; E-mail: cjbshl @PEG70, the molar ratio of163. comHAjYHCNMH Gm was 18 hSeso* Coreponding author: XU Zheng(徐政):Prof.; Ph D; E-mail:ly, it was measured with different molar ratio of 1/10, 1/xuzhengl 178@ yahoo. com. cn* Funded by the“Fifteen"63 Project( No. 2002AA205091)5, 1/3 and 1/2 with PEG Mw 6 000 and reaction time164Journal of Wuhan University of Technology - Mater. Sci. Ed.Dec.2005was 18 h.6000, 20 000). Its characteristic viscosities decreased2.4 Viscoelasticity of HA derivative testingith the increasing of PEG molecular weight, whichWith different non-ion aqueous solution with massshowed the reactive cross- linkage degree decreased withfraction of0. 5%, 1% and 1.5%,the dynamic mechan-the increasing of PEG molecular weight. HA' s structureics properties of the HA derivative and its viscoelasticin aqueous solution was a reticulation one and the PEGchanges were studied with 3ARES3 Rheometer (Japan) atmolecules passed through the space between net-like25CwithPEGMw6000.structure to get to the suitable amino position to causecross -linking reaction with HA. PEG with higher molecu-3 Results and Discussionlar weight had usual larger volume. But the space was rel-atively easier for passing as PEG with smaller volume and3.1 Characteristic and dynamic viscosity testingmay cause cross linking HA derivative with much higherFig. 1 showed characteristic viscosities of HA deri-molecular weight. From the testing of dynamic viscosity,vale with diferent reaction times. We knew that charac-the completely opposite results appeared ( Fig.3). Thetenistic viscosity of HA derivative had the biggest value inHA derivative aqueous dynamic viscosity increased with12 h, which meant cross linkage degree between HA ande increment of PEG molecular weight. Under highPEG was the largest in 12 h. HA and PEG didn't com-shearing rate, the HA molecule would be lengthened andpletely crosslink before 6 h, but after 12 h, HA and itsthe solution viscosity was seen as a result between HA lin-derivative degraded gradually with reaction times going onear molecules' friction and the value was not deteminedunder alkali reaction condition. So we concluded due toby molecular weight but by the space size between adja-degradation function, characteristic viscosities of HA deri-cent molecule. For the same mass fraction of HA deriva-vative decreased after 12 hours reaction time. And thetive solution (0. 4%), the higher Mw solution had lowerchanging rate of characteristic visoosity was relatively slowmolecule concentration and lower dynamic viscosity as thejust with the relative slow reactants degradation'。relative less frictidn probability between adjacentFig.2 showed characteritic viscosity of HA deriva-molecules8.9]tives with different PEG relative molecular weight ( 400,6000,5000台1400030002000of -400. .6000. .20000Relative molecularweight ofPECFig1 Charateristie: viscosity of HA derivative Fig.2 Characteristic viscosity ofHA derivative Fig.3 Dynamic viscosity of HA derivativewith different reaction timeswith diferent PEG Mwwith different PEG Mw可50004800; 46004 400宣10-4 20033 8003600”32000.0.2.03. 0.4- 0.50.2.0.300.5Molar ratio of HAIPEGMolar ratio of HAPEGFig.4 Characteristic viscosity of HA derivative withFig.5 Dynamic viscosity of HA derivative with diferentdiferent molar ratio of HA/PEGmolar ratio of HA/PEGFigs. 4,5 showed the characteristic and dynamielik中国煤化工asily fomed in aque-viscosity of HA derivative with diferent molar ratio of HA/ousMHCNMH G But with the higher .PEG. With the increment of PEG adding, the cross-link-molar rato ot HA/PEU, and the much appearance of low-age degree changed. With the lower molar ratio of HA/er molecule, the efect was quite the opposite. With thePEG, cross-linking function of PEG to HA was quite ob-continuous increment of molar ratio of HA/PEG, the reac-vious and derivative had higher molecular weight and net-tion cross-linkage enhanced, the medium and lower mole-Vol.20 Suppl.CHEN Jinghua et al :Characteristics of Hyaluronie Acid Derivative Cross-linked....165cule of HA derivative increased and the friction probabilityceeded fixed value, molecule can not untie twist each oth-between different molecules subsequently increased toer without enough time, so elasticity was its most charac-cause the viscosity higher. With the further increment ofter. This fixed value was its intersection point from vis-molar ratio of HA/PEG, the CrOss- linking function of PEGcosity to elasticity. With the increment of solution concen-to HA reduced accordingly, and net-like structure as onetration, the position of crossing point changed to be lowerunit could not be formed with the domination of lowerand lower. This showed increasing of HA derivative con-molecule and viscosity was lessenedoI .centration reduced crossing frequency and enhance solu-3.2 The change relationship between viscosity andtion' s elasticityelasticity of solutionThe compare of the crossing point frequency of HAThe conversion relationship between viscosity withand its derivative was showed in Figs. 6, 7. Under theelasticity of HA derivative solution with vibrated frequencysame concentration, the changing point frequency fromchanging was shown in Fig. 6. The conversion from loviscosity to elasticity for HA was higher than for HA deni-vibrated frequency to high vibrated frequency for solutionvative. This was caused by different overlapping degreeequals from viscosity to elasticity, because molecule canbetween different molecule chains for different HA anduntie twist each other at low vibrated frequency. Its mainHA derivative, the ltter overlapping was more difcult tocharacter was viscosity, but when vibrated frequency ex-be opened.1.2r1.0 ■15-0.0.0■1.5 water0.0●1.0water .f 0.8上▲0.5卓0.8F ▲0.5water20.6-0.6+0.504F105504F0.2|-0.80.001 0.01.10 100 10000.110 10Freq(rod-s) ;Freq(rod-s)Fig.6 Trend of HA derivative from viscosity to elasticityFig.7 Trend of HA from viscosity to elasticity[ 3] Wangwenbin, Guqisheng, Wuping, et al. Application and4 ConclusionsDevelopment of Visoelastic Reagent of Ophthalmology . Jour-nal of Injuries and Occupational Diseses of the Eye with Oph-thalmic Surgeries ,00022(1):114-117From all above testing, we knew characteristic vis-[4] Chen Jinghua, Xu Zheng, Gu Qisheng, Lin Cong. Researchcosities of HA derivative had the largest value in 12 hon Rheological Property of Hyaluronic Aeid Derivative Cross-within this experiment condition, which decreased withlinked by Polyethylene Glycol. Jounal of Tongi Uniersity,the increasing of PEG molecular weight. But HA deriva-2005 ,43(1)111-116tive aqueous dynamic viscosity increased with the incre- [5] Ambrosio L A, BrachieloP A, Netti P A, Nicolais Lment of PEG molecular weight. In terms of viscoelasticityProperties of New Materials: Rheological Sudy on HyaluronicAcid and Its Derivative Solutions. JMS Pure and Appliedrelationship, the conversion from low vibrated frequencyChemistry, 199, A36(718) :91-10000to high vibrated frequency of solution resulted in change[6] Bealas E A,Leshchiner E. Cos-linked Gels of Hyaluronic Ac-from viscosity to elasticity of solution, and higher HA de-id and Products. uS Patent No. 4582865 , 1984-02-24rivative concentration can reduce crossing frequency and[7] Gibbs DA, Meril EW, Smith KA, et al . Rheology of Hyalu-enhance solution' s elasticity. Above all, as to the rheo-ronic Acid. Biopolymer , 1968.6777-782logical properties, the structure modified HA derivative[8] Ling Peixue. Hyaluronic Acid. Bejing:Chinese Light Industrycan meet the requirement of biomaterial and be safelyPes,2000[9] Wik B H, Wik 0. Rheology of Hyaluronan and Its Deriva-used in clinical medical field.tive. The Chemisty , Biology and Medical Aplicatins of Hy-aluronan and Ils Derioatives. London: Portland Press, 1998,References45:25-32[1] Nicolai Bohm. Rheological Studies of Barley(1→3)(1-→4)-[10]中国煤化工Structure of a Fully Ex-id Sodium Salt and Com-B-glucan in Concentrated Solution. Mechanistic and KineticHC N M H Gald Helial Forms. Biol-Inuestigation of the Gel Formatin Carbohydrate Research,polymer , 1975,99:219-2351999 ,315: 302-310[11] Balazs E A. The Viscoelastic Inerellular Matrix and Con-[2] Kim BS, Mooney DJ. Development of Biocompatible Synthel-trol of Cell Function by Hyaluronan. The Chemistry, Biologyic Extaelular Matrices for Tissue Engineering. Trends Bio-and Medical Application of Hyaluronan and Its Derivatives .technol ., 1998, 16(5) :224-229London: Portland Press, 1998: 185-204

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