用于软骨缺损修复的壳聚糖水凝胶降解性能的表征
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摘要
背景:壳聚糖水凝胶修复软骨缺损生物相容性好,但目前尚不明确壳聚糖水凝胶在软骨缺损修复过程中的降解性能变化。目的:探讨壳聚糖水凝胶在软骨缺损修复过程中的降解性能变化。方法:采用羟乙基脱乙酰壳多糖(glycolchitosan,GC)与二醛基聚乙二醇(OHC-PEG-CHO)通过席夫碱反应交联,形成可注射水凝胶。考察不同浓度的水凝胶(GC/OHC-PEG-CHO:2 wt%/2 wt%和2 wt%/1 wt%)在体外降解中的pH值、质量和体积变化。结果:水凝胶在降解过程中,pH值基本维持在7左右;水凝胶(GC/OHC-PEG-CHO:2 wt%/1 wt%)在6周时全部降解,而水凝胶(GC/OHC-PEG-CHO:2 wt%/2 wt%)在8周时质量为初始质量的44.30%±5.51%,体积为初始体积的50.64%±9.81%,该降解速度与软骨修复速率一致。选取水凝胶(GC/OHC-PEG-CHO:2 wt%/2 wt%)植入新西兰大白兔皮下,组织学切片分析结果表明,3周时水凝胶明显变小,但无明显的炎症反应。结论:初步降解实验表明GC/OHC-PEG-CHO水凝胶可用于软骨缺损修复。
Background: Chitosan hydrogel can repair the cartilage defect because of its good biocompatibility, but it is notclear how the degradation properties of chitosan hydrogel change in the process of cartilage defects. Objective: To investigatethe changes of degradation property of chitosan hydrogel in the process of cartilage defects. Methods: Glycol chitosan(GC) anddialdehyde polyethylene glycol(OHC-PEG-CHO) were dynamically cross-linked to form an injectable hydrogel by Schiffbase reaction. In vitro degradation experiments, potential of hydrogen pH value, weight and volume changes of the hydrogel atdifferent concentrations(GC/OHC-PEG-CHO: 2 wt%/2 wt% and 2 wt%/1 wt%) were examined. Results: The pH value of thehydrogel maintained at about 7 and the hydrogel were all degraded at 6 weeks in vitro with 2 wt% GC and 1 wt% OHC-PEG-CHO. The weight and volume of the hydrogel with 2 wt% GC and 2 wt% OHC-PEG-CHO were 44.30%±5.51% and 50.64%±9.81% of the initial hydrogel at 8 weeks in vitro, respectively, which was in accordance with the cartilage repair rate. Further-more, the hydrogel with 2 wt% GC and 2 wt% OHC-PEG-CHO was subcutaneously embedded in New Zealand white rabbitsto detect the degradation in vivo. The results of histological analysis showed that the hydrogel obviously became small and nosevere inflammation was found at 3 weeks after in vivo experiment. Conclusions: Preliminary degradation experiments showthat GC/OHC-PEG-CHO hydrogel can be applied to repair cartilage defects.
Background: Chitosan hydrogel can repair the cartilage defect because of its good biocompatibility, but it is notclear how the degradation properties of chitosan hydrogel change in the process of cartilage defects. Objective: To investigatethe changes of degradation property of chitosan hydrogel in the process of cartilage defects. Methods: Glycol chitosan(GC) anddialdehyde polyethylene glycol(OHC-PEG-CHO) were dynamically cross-linked to form an injectable hydrogel by Schiffbase reaction. In vitro degradation experiments, potential of hydrogen pH value, weight and volume changes of the hydrogel atdifferent concentrations(GC/OHC-PEG-CHO: 2 wt%/2 wt% and 2 wt%/1 wt%) were examined. Results: The pH value of thehydrogel maintained at about 7 and the hydrogel were all degraded at 6 weeks in vitro with 2 wt% GC and 1 wt% OHC-PEG-CHO. The weight and volume of the hydrogel with 2 wt% GC and 2 wt% OHC-PEG-CHO were 44.30%±5.51% and 50.64%±9.81% of the initial hydrogel at 8 weeks in vitro, respectively, which was in accordance with the cartilage repair rate. Further-more, the hydrogel with 2 wt% GC and 2 wt% OHC-PEG-CHO was subcutaneously embedded in New Zealand white rabbitsto detect the degradation in vivo. The results of histological analysis showed that the hydrogel obviously became small and nosevere inflammation was found at 3 weeks after in vivo experiment. Conclusions: Preliminary degradation experiments showthat GC/OHC-PEG-CHO hydrogel can be applied to repair cartilage defects.
引文
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[11]Bian L, Guvendiren M, Mauck RL, et al. Hydrogels thatmimic developmentally relevant matrix and N-cadherin in-teractions enhance MSC chondrogenesis. Proc Natl Acad SciUSA, 2013, 110(25):10117-10122.
[12]Mirahmadi F, Tafazzoli-Shadpour M, Shokrgozar MA, et al.Enhanced mechanical properties of thermosensitive chitosanhydrogel by silk fibers for cartilage tissue engineering. Ma-ter Sci Eng C Mater Biol Appl, 2013, 33(8):4786-4794.
[13]Choi B, Kim S, Lin B, et al. Cartilaginous extracellular ma-trix-modified chitosan hydrogels for cartilage tissue engi-neering. ACS Appl Mater Interfaces, 2014, 6(22):20110-20121.
[14]Sechriest VF, Miao YJ, Niyibizi C, et al. GAG-augmentedpolysaccharide hydrogel:a novel biocompatible and biode-gradable material to support chondrogenesis. J Biomed Ma-ter Res, 2000, 49(4):534-541.
[15]Ding C, Zhao L, Liu F, et al. Dually responsive injectablehydrogel prepared by in situ cross-linking of glycol chitosanand benzaldehyde-capped PEO-PPO-PEO. Biomacromole-cules, 2010, 11(4):1043-1051.
[16]Zhu F, Chen Y, Yang S, et al. Surface patterned hydrogelfilm as a flexible scaffold for 2D and 3D cell co-culture.RSC Adv, 2016, 6(66):61185-61189.
[2]Hunziker EB. Articular cartilage repair:basic science andclinical progress. A review of the current status and pros-pects. Osteoarthritis Cartilage, 2002, 10(6):432-463.
[3]Yang J, Zhang YS, Yue K, et al. Cell-laden hydrogels for os-teochondral and cartilage tissue engineering. Acta Biomater,2017, 57(15):1-25.
[4]Nukavarapu SP, Dorcemus DL. Osteochondral tissue engi-neering:current strategies and challenges. Biotechnol Adv,2013, 31(5):706-721.
[5]Spiller KL, Maher SA, Lowman AM. Hydrogels for the repairof articular cartilage defects. Tissue Eng Part B Rev, 2011,17(4):281-299.
[6]Ahearne M, Kelly DJ. A comparison of fibrin, agarose andgellan gum hydrogels as carriers of stem cells and growth fac-tor delivery microspheres for cartilage regeneration. BiomedMater, 2013, 8(3):035004.
[7]Mauck RL, Byers BA, Yuan X, et al. Regulation of cartilagi-nous ECM gene transcription by chondrocytes and MSCs in3D culture in response to dynamic loading. Biomech ModelMechanobiol, 2007, 6(1-2):113-125.
[8]Williams GM, Klein TJ, Sah RL. Cell density alters matrixaccumulation in two distinct fractions and the mechanical in-tegrity of alginate-chondrocyte constructs. Acta Biomater,2005, 1(6):625-633.
[9]Ahearne M, Buckley CT, Kelly DJ. A growth factor deliverysystem for chondrogenic induction of infrapatellar fat padderived stem cells in fibrin hydrogels. Biotechnol Appl Bio-chem, 2011, 58(5):345-352.
[10]Jin R, Moreira Teixeira LS, Krouwels A, et al. Synthesis andcharacterization of hyaluronic acid-poly(ethylene glycol)hydrogels via michael addition:An injectable biomaterialfor cartilage repair. Acta Biomater, 2010, 6(6):1968-1977.
[11]Bian L, Guvendiren M, Mauck RL, et al. Hydrogels thatmimic developmentally relevant matrix and N-cadherin in-teractions enhance MSC chondrogenesis. Proc Natl Acad SciUSA, 2013, 110(25):10117-10122.
[12]Mirahmadi F, Tafazzoli-Shadpour M, Shokrgozar MA, et al.Enhanced mechanical properties of thermosensitive chitosanhydrogel by silk fibers for cartilage tissue engineering. Ma-ter Sci Eng C Mater Biol Appl, 2013, 33(8):4786-4794.
[13]Choi B, Kim S, Lin B, et al. Cartilaginous extracellular ma-trix-modified chitosan hydrogels for cartilage tissue engi-neering. ACS Appl Mater Interfaces, 2014, 6(22):20110-20121.
[14]Sechriest VF, Miao YJ, Niyibizi C, et al. GAG-augmentedpolysaccharide hydrogel:a novel biocompatible and biode-gradable material to support chondrogenesis. J Biomed Ma-ter Res, 2000, 49(4):534-541.
[15]Ding C, Zhao L, Liu F, et al. Dually responsive injectablehydrogel prepared by in situ cross-linking of glycol chitosanand benzaldehyde-capped PEO-PPO-PEO. Biomacromole-cules, 2010, 11(4):1043-1051.
[16]Zhu F, Chen Y, Yang S, et al. Surface patterned hydrogelfilm as a flexible scaffold for 2D and 3D cell co-culture.RSC Adv, 2016, 6(66):61185-61189.