软骨组织工程用羧甲基壳聚糖/氧化海藻酸钠复合水凝胶的制备及体外评估

doi:10.7518/hxkq.2019.03.005

华西口腔医学杂志 ›› 2019, Vol. 37 ›› Issue (3): 253-259.doi: 10.7518/hxkq.2019.03.005

软骨组织工程用羧甲基壳聚糖/氧化海藻酸钠复合水凝胶的制备及体外评估

李云洁¹,滕彬宏¹,赵艳红¹(),杨强²,王连永³,黄颖¹

1.天津医科大学口腔医院正畸科,天津 300070
2.天津医院脊柱外科,天津 300211
3.南开大学生命科学学院生物活性材料教育部重点实验室,天津 300071

收稿日期:2018-12-15 修回日期:2019-03-10 出版日期:2019-06-01 发布日期:2019-06-12
通讯作者: 赵艳红 E-mail:leafzh@126.com
作者简介:李云洁,硕士,E-mail:250883893@qq.com
基金资助:
国家自然科学基金(31300798);国家自然科学基金(31470937);国家自然科学基金(81572154);天津市卫生局科技攻关重点项目(15KG125);天津市卫生局科技攻关重点项目(16KG114)

Preparation and evaluation of carboxymethyl chitosan/sodium alginate hydrogel for cartilage tissue engineering

Yunjie Li¹,Binhong Teng¹,Yanhong Zhao¹(),Qiang Yang²,Lianyong Wang³,Ying Huang¹

1.Dept. of Orthodontics, Stomatological Hospital of Tianjin Medical University, Tianjin 300070, China
2.Dept. of Spine Surgery, Tianjin Hospital, Tianjin 300211, China
3.The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China

Received:2018-12-15 Revised:2019-03-10 Online:2019-06-01 Published:2019-06-12
Contact: Yanhong Zhao E-mail:leafzh@126.com
Supported by:
The National Science Foundation of China(31300798);The National Science Foundation of China(31470937);The National Science Foundation of China(81572154);The Research Foundation of Tianjin Health Bureau(15KG125);The Research Foundation of Tianjin Health Bureau(16KG114)

摘要/Abstract

摘要：

目的优化羧甲基壳聚糖/氧化海藻酸钠（CMCS/OSA）复合水凝胶制备工艺,并应用于软骨组织工程。方法制备氨基与醛基比例分别为2:1、1:1、1:2的CMCS/OSA复合水凝胶,并通过扫描电子显微镜观察、流变学检测、黏附拉力测试、溶胀率分析及细胞实验等方法评价复合水凝胶的微观形态、物理特性以及生物相容性,以制备满足软骨再生领域需求的水凝胶。结果氨基与醛基比为1:1时,制备出的水凝胶具有良好的孔隙率、适宜的成胶时间、较强的黏附力及稳定的溶胀率等性质,对细胞有良好的生物相容性。结论氨基与醛基比为1:1时制备出的CMCS/OSA复合水凝胶是软骨组织工程优异的支架材料。

关键词: 羧甲基壳聚糖, 氧化海藻酸钠, 水凝胶, 脐带间充质干细胞, 软骨组织工程

Abstract:

Objective This study aimed to optimize the preparation of carboxymethyl chitosan/sodium alginate (CMCS/OSA) compound hydrogels. This study also aimed to investigate the applicability of the hydrogels in cartilage tissue engineering. Methods Three groups of CMCS/OSA composite hydrogels with amino-to-aldehyde ratios of 2:1, 1:1 and 1:2 were prepared. The microstructure, physical properties, and cell biocompatibility of the three groups of CMCS/OSA composite hydrogels were evaluated. Samples were subjected to scanning electron microscopy, rheological test, adhesion tension test, swelling rate test, and cell experiments to identify the CMCS/OSA composite hydrogel with the cross-linking degree that can meet the requirements for scaffolds in cartilage tissue engineering. Results The experimental results showed that the CMCS/OSA hydrogel with a amine-to-aldhyde ratio of 1:1 had good porosity, suitable gelling time, strong adhesive force, stable swelling rate, and good cellular biocompatibility. Conclusion The CMCS/OSA compound hydrogel prepared with a 1:1 ratio of amino and aldehyde groups has potential applications in cartilage tissue engineering.

Key words: carboxymethyl chitosan, sodium alginate, hydrogel, umbilical cord mesenchymalstem cell, cartilage tissue engineering

中图分类号:

R781.1

李云洁,滕彬宏,赵艳红,杨强,王连永,黄颖. 软骨组织工程用羧甲基壳聚糖/氧化海藻酸钠复合水凝胶的制备及体外评估[J]. 华西口腔医学杂志, 2019, 37(3): 253-259.

Yunjie Li,Binhong Teng,Yanhong Zhao,Qiang Yang,Lianyong Wang,Ying Huang. Preparation and evaluation of carboxymethyl chitosan/sodium alginate hydrogel for cartilage tissue engineering[J]. West China Journal of Stomatology, 2019, 37(3): 253-259.

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参考文献 31

[1]	Abrahamsson AK, Kristensen M, Arvidsson LZ , et al. Frequency of temporomandibular joint osteoarthritis and related symptoms in a hand osteoarthritis cohort[J]. Osteoarthr Cartil, 2017,25(5):654-657. doi: 10.1016/j.joca.2016.12.028 URL
[2]	Nitzan DW, Svidovsky J, Zini A , et al. Effect of arthrocentesis on symptomatic osteoarthritis of the temporomandibular joint and analysis of the effect of preoperative clinical and radiologic features[J]. J Oral Maxillofac Surg, 2017,75(2):260-267. doi: 10.1016/j.joms.2016.08.017 URL
[3]	Zhou YG, Chyu J, Zumwalt M . Recent progress of fabrication of cell scaffold by electrospinning technique for articular cartilage tissue engineering[J]. Int J Biomater, 2018: 1953636.
[4]	Xie XP, Zhang Q, Zhou TF , et al. The review of nanomaterials inducing the differentiation of stem cells into chondrocyte phenotypes in cartilage tissue engineering[J]. Curr Stem Cell Res Ther, 2018,13(7):600-607. doi: 10.2174/1574888X13666180511164509 URL
[5]	Gurer B, Cabuk S, Karakus O , et al. In vivo cartilage tissue engineering[J]. J Orthop Surg Res, 2018,13(1):107. doi: 10.1186/s13018-018-0823-0
[6]	Jiang XF, Liu JT, Liu Q , et al. Correction: therapy for cartilage defects: functional ectopic cartilage constructed by cartilage-simulating collagen, chondroitin sulfate and hyaluronic acid (CCH) hybrid hydrogel with allogeneic chondrocytes[J]. Biomater Sci, 2018,6(6):1616-1626. doi: 10.1039/C8BM00354H URL
[7]	Qi C, Liu J, Jin Y , et al. Photo-crosslinkable, injectable sericin hydrogel as 3D biomimetic extracellular matrix for minimally invasive repairing cartilage[J]. Biomaterials, 2018,163:89-104. doi: 10.1016/j.biomaterials.2018.02.016 URL
[8]	Radhakrishnan J, Subramanian A, Sethuraman S . Injectable glycosaminoglycan-protein nano-complex in semi-interpenetrating networks: a biphasic hydrogel for hyaline cartilage regeneration[J]. Carbohydr Polym, 2017,175:63-74. doi: 10.1016/j.carbpol.2017.07.063 URL
[9]	Zhou TF, Li XL, Li G , et al. Injectable and thermosensitive TGF-β1-loaded PCEC hydrogel system for in vivo cartilage repair[J]. Sci Rep, 2017,7(1):10553. doi: 10.1038/s41598-017-11322-w URL pmid: 28874815
[10]	Chen WL, Li CH, Peng M , et al. Autologous nasal chondrocytes delivered by injectable hydrogel for in vivo articular cartilage regeneration[J]. Cell Tissue Bank, 2018,19(1):35-46. doi: 10.1007/s10561-017-9649-y URL
[11]	Chen F, Ni YZ, Liu B , et al. Self-crosslinking and injectable hyaluronic acid/RGD-functionalized pectin hydrogel for cartilage tissue engineering[J]. Carbohydr Polym, 2017,166:31-44. doi: 10.1016/j.carbpol.2017.02.059 URL
[12]	Treenate P, Monvisade P . In vitro drug release profiles of pH-sensitive hydroxyethylacryl chitosan/sodium alginate hydrogels using paracetamol as a soluble model drug[J]. Int J Biol Macromol, 2017,99:71-78. doi: 10.1016/j.ijbiomac.2017.02.061 URL
[13]	Wang YY, Peng WZ, Liu X , et al. Study of bilineage differentiation of human-bone-marrow-derived mesenchymal stem cells in oxidized sodium alginate/N-succinyl chitosan hydrogels and synergistic effects of RGD modification and low-intensity pulsed ultrasound[J]. Acta Biomater, 2014,10(6):2518-2528. doi: 10.1016/j.actbio.2013.12.052 URL
[14]	Rassu G, Salis A, Porcu EP , et al. Composite chitosan/alginate hydrogel for controlled release of deferoxamine: a system to potentially treat iron dysregulation diseases[J]. Carbohydr Polym, 2016,136:1338-1347. doi: 10.1016/j.carbpol.2015.10.048 URL
[15]	Bu Y, Xu HX, Li X , et al. A conductive sodium alginate and carboxymethyl[J]. RSC Adv, 2018,8:10806-10817. doi: 10.1039/C8RA01059E URL
[16]	Li Y, Cao J, Han S , et al. ECM based injectable thermo-sensitive hydrogel on the recovery of injured cartilage induced by osteoarthritis[J]. Artif Cells Nanomed Biotechnol, 2018,46(Suppl 2):152-160. doi: 10.1080/21691401.2018.1452752 URL
[17]	Naghizadeh Z, Karkhaneh A, Khojasteh A . Simultaneous release of melatonin and methylprednisolone from an injectable in situ self-crosslinked hydrogel/microparticle system for cartilage tissue engineering[J]. J Biomed Mater Res A, 2018,106(7):1932-1940. doi: 10.1002/jbm.a.v106.7 URL
[18]	Boyer C, Figueiredo L, Pace R , et al. Laponite nanoparticle-associated silated hydroxypropylmethyl cellulose as an injectable reinforced interpenetrating network hydrogel for cartilage tissue engineering[J]. Acta Biomater, 2018,65:112-122. doi: 10.1016/j.actbio.2017.11.027 URL
[19]	Chen F, Yu SR, Liu B , et al. An injectable enzymatically crosslinked carboxymethylated Pullulan/Chondroitin sulfate hydrogel for cartilage tissue engineering[J]. Sci Rep, 2016,6:20014.
[20]	Comblain F, Rocasalbas G, Gauthier S , et al. Chitosan: a promising polymer for cartilage repair and viscosupplementation[J]. Biomed Mater Eng, 2017,28(s1):209-215. doi: 10.3233/BME-171643 URL pmid: 28372297
[21]	Muzzarelli RA, El Mehtedi M, Bottegoni C , et al. Genipin-crosslinked chitosan gels and scaffolds for tissue engineering and regeneration of cartilage and bone[J]. Mar Drugs, 2015,13(12):7314-7338. doi: 10.3390/md13127068 URL
[22]	Meng QY, Man ZT, Dai LH , et al. A composite scaffold of MSC affinity peptide-modified demineralized bone matrix particles and chitosan hydrogel for cartilage regeneration[J]. Sci Rep, 2015,5:17802.
[23]	Zhao M, Chen Z, Liu K , et al. Repair of articular cartilage defects in rabbits through tissue-engineered cartilage constructed with chitosan hydrogel and chondrocytes[J]. J Zhejiang Univ Sci B, 2015,16(11):914-923. doi: 10.1631/jzus.B1500036 URL
[24]	García-López J, Garciadiego-Cázares D, Melgarejo-Ramírez Y , et al. Chondrocyte differentiation for auricular cartilage reconstruction using a chitosan based hydrogel[J]. Histol Histopathol, 2015,30(12):1477-1485. doi: 10.14670/HH-11-642 pmid: 26119536
[25]	莫湘涛, 邓力, 李秀群 , 等. 软骨细胞-海藻酸钠水凝胶-SIS复合体修复全层关节软骨缺损的实验研究[J]. 中国修复重建外科杂志, 2009,23(8):974-979.
	Mo XT, Deng L, Li XQ , et al. Experimental study of repairing full-thickness articular cartilage defect with chondrocyte-sodium alginate hydrogel-SIS complex[J]. Chin J Reparat Reconstruct Surg, 2009,23(8):974-979.
[26]	Miralles G, Baudoin R, Dumas D , et al. Sodium alginate sponges with or without sodium hyaluronate: in vitro engineering of cartilage[J]. J Biomed Mater Res, 2001,57(2):268-278. doi: 10.1002/(ISSN)1097-4636 URL
[27]	Pelletier S, Hubert P, Payan E , et al. Amphiphilic derivatives of sodium alginate and hyaluronate for cartilage repair: rheological properties[J]. J Biomed Mater Res, 2001,54(1):102-108. doi: 10.1002/(ISSN)1097-4636 URL
[28]	Yu W, Liu Y, Sheng N , et al. A soft tissue adhesive based on aldehyde-sodium alginate[J]. Front Mater Sci, 2017,11(3):215-222.
[29]	Wu Y, Yuan L, Sheng NA , et al. A soft tissue adhesive based on aldehyde-sodium alginate and amino-carboxymethyl chitosan preparation through the Schiff reaction[J]. Front Mater Sci, 2017,11(3):215-222.
[30]	Sadlik B, Jaroslawski G, Puszkarz M , et al. Cartilage repair in the knee using umbilical cord wharton’s jelly-derived mesenchymal stem cells embedded onto collagen scaffolding and implanted under dry arthroscopy[J]. Arthrosc Tech, 2018,7(1):e57-e63. doi: 10.1016/j.eats.2017.08.055 URL
[31]	Desancé M, Contentin R, Bertoni L , et al. Chondrogenic differentiation of defined equine mesenchymal stem cells derived from umbilical cord blood for use in cartilage repair therapy[J]. Int J Mol Sci, 2018, 19(2). pii: E537. doi: 10.3390/ijms19020537 URL

软骨组织工程用羧甲基壳聚糖/氧化海藻酸钠复合水凝胶的制备及体外评估

Preparation and evaluation of carboxymethyl chitosan/sodium alginate hydrogel for cartilage tissue engineering

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