软骨修复中壳聚糖复合水凝胶的应用与价值
|
摘要
背景:壳聚糖以广泛的生物来源、简单的制备工艺及优良的生物相容性成为软骨修复材料的研究热点之一。目的:围绕壳聚糖类复合水凝胶的特点及在软骨修复中的应用展开综述。方法:应用计算机检索PubMed数据库和CNKI数据库,中文关键词为"壳聚糖,壳聚糖水凝胶,软骨修复,组织工程",英文检索词为"chitosan;chitosan Hydrogels;Cartilage repair;tissue engineering",检索2000年1月至2018年3月发表的文献,将所有文章进行初步筛选后,对保留的文章进一步详细分析、归纳并总结。结果与结论:壳聚糖具有良好的生物相容性、低毒性、低免疫原性,在不同的物理或化学的改良下可负载多种生长因子、种子细胞,在组织工程软骨修复中取得了令人可喜的进展。随着科技的进步及对软骨及软骨下骨组织结构的了解,壳聚糖仿生水凝胶拓宽了壳聚糖的应用范围。但随着研究的进一步推进,壳聚糖在体内修复的分子机制、降解过程仍然存在很多争议,需要广大学者进一步的研究与探索。
BACKGROUND: Chitosan has become a research hotspot of cartilage repair materials because of a wide range of biological sources, simple preparation processes and excellent biocompatibility. OBJECTIVE: To review the characteristics of chitosan hydrogels and their application in cartilage repair. METHODS: PubMed and CNKI databases were searched by computer with the keywords of "chitosan; chitosan hydrogel; cartilage repair; tissue engineering" in English and Chinese, respectively. The time range was from January 2000 to March 2018. After initial screening, the retained articles were further analyzed, concluded and summarized. RESULTS AND CONCLUSION: Chitosan has good biocompatibility, low toxicity, low immunogenicity, and can load multiple growth factors and seed cells with different physical or chemical improvements. Encouraging progress in tissue engineering cartilage repair has been achieved. With the development of technology and the understanding of cartilage and subchondral bone structure, the application range of chitosan biomimetic hydrogel has been broadened. However, the molecular mechanism and degradation process of chitosan in vivo still have a lot of controversies, and further research and exploration are needed.
BACKGROUND: Chitosan has become a research hotspot of cartilage repair materials because of a wide range of biological sources, simple preparation processes and excellent biocompatibility. OBJECTIVE: To review the characteristics of chitosan hydrogels and their application in cartilage repair. METHODS: PubMed and CNKI databases were searched by computer with the keywords of "chitosan; chitosan hydrogel; cartilage repair; tissue engineering" in English and Chinese, respectively. The time range was from January 2000 to March 2018. After initial screening, the retained articles were further analyzed, concluded and summarized. RESULTS AND CONCLUSION: Chitosan has good biocompatibility, low toxicity, low immunogenicity, and can load multiple growth factors and seed cells with different physical or chemical improvements. Encouraging progress in tissue engineering cartilage repair has been achieved. With the development of technology and the understanding of cartilage and subchondral bone structure, the application range of chitosan biomimetic hydrogel has been broadened. However, the molecular mechanism and degradation process of chitosan in vivo still have a lot of controversies, and further research and exploration are needed.
引文
[1]Zhu J,Marchant RE.Design properties of hydrogel tissue-engineering scaffolds.Expert Rev Med Devices.2011;8(5):607-626.
[2]Oryan A,Sahvieh S.Effectiveness of chitosan scaffold in skin,bone and cartilage healing.Int J Biol Macromol.2017;104(Pt A):1003-1011.
[3]徐敬,赵建宁,徐海栋,等.壳聚糖及其衍生物在软骨组织工程中的应用[J].中国组织工程研究,2015,19(25):4081-4085.
[4]陈道玉,张中民,姜丽丽.壳聚糖支架材料在组织工程中的应用与未来[J].中国组织工程研究,2017,21(30):4893-900.
[5]Ali A,Ahmed S.A review on chitosan and its nanocomposites in drug delivery.Int J Biol Macromol.2018;109:273-286.
[6]Rodríguez-Vázquez M,Vega-Ruiz B,Ramos-Zú?iga R,et al.Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine.Biomed Res Int.2015;2015:821279.
[7]Radhakrishnan J,Subramanian A,Krishnan UM,et al.Injectable and 3D Bioprinted Polysaccharide Hydrogels:From Cartilage to Osteochondral Tissue Engineering.Biomacromolecules.2017;18(1):1-26.
[8]Nukavarapu SP,Dorcemus DL.Osteochondral tissue engineering:current strategies and challenges.Biotechnol Adv.2013;31(5):706-721.
[9]Ahmed S,Annu,Ali A,et al.A review on chitosan centred scaffolds and their applications in tissue engineering.Int J Biol Macromol.2018;116:849-862.
[10]傅月荷,吕青.生物来源水凝胶在组织工程中的应用与进展[J].中国修复重建外科杂志,2014,28(8):1030-1036.
[11]Chenite A,Chaput C,Wang D,et al.Novel injectable neutral solutions of chitosan form biodegradable gels in situ.Biomaterials.2000;21(21):2155-2161.
[12]康肸,邓爱鹏,杨树林.壳聚糖基温敏水凝胶的研究进展[J].中国生物工程杂志,2018,38(5):79-84.
[13]Wu J,Liu J,Shi Y,et al.Rheological,mechanical and degradable properties of injectable chitosan/silk fibroin/hydroxyapatite/glycerophosphate hydrogels.J Mech Behav Biomed Mater.2016;64:161-172.
[14]Song K,Li L,Yan X,et al.Characterization of human adipose tissue-derived stem cells in vitro culture and in vivo differentiation in a temperature-sensitive chitosan/β-glycerophosphate/collagen hybrid hydrogel.Mater Sci Eng CMater Biol Appl.2017;70(Pt 1):231-240.
[15]Deng A,Kang X,Zhang J,et al.Enhanced gelation of chitosan/β-sodium glycerophosphate thermosensitive hydrogel with sodium bicarbonate and biocompatibility evaluated.Mater Sci Eng C Mater Biol Appl.2017;78:1147-1154.
[16]Su JY,Chen SH,Chen YP,et al.Evaluation of Magnetic Nanoparticle-Labeled Chondrocytes Cultivated on a Type Ⅱ Collagen-Chitosan/Poly(Lactic-co-Glycolic)Acid Biphasic Scaffold.Int J Mol Sci.2017;18(1).pii:E87.doi:10.3390/ijms18010087.
[17]Chen Z,Zhao M,Liu K,et al.Novel chitosan hydrogel formed by ethylene glycol chitosan,1,6-diisocyanatohexan and polyethylene glycol-400 for tissue engineering scaffold:in vitro and in vivo evaluation.J Mater Sci Mater Med.2014;25(8):1903-1913.
[18]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.JZhejiang Univ Sci B.2015;16(11):914-923.
[19]Oussedik S,Tsitskaris K,Parker D.Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation:a systematic review.Arthroscopy.2015;31(4):732-744.
[20]Man Z,Hu X,Liu Z,et al.Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.Biomaterials.2016;108:157-167.
[21]Song K,Li L,Yan X,et al.Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold.J Mater Sci Mater Med.2016;27(6):114.
[22]刘相杰,宋科官.生物支架材料及间充质干细胞在骨组织工程中的研究与应用[J].中国组织工程研究,2018,22(10):1618-24.
[23]Dai R,Wang Z,Samanipour R,et al.Adipose-Derived Stem Cells for Tissue Engineering and Regenerative Medicine Applications.Stem Cells Int.2016;2016:6737345.
[24]Tamaddon M,Burrows M,Ferreira SA,et al.Monomeric,porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro.Sci Rep.2017;7:43519.
[25]Yang J,Zhang YS,Yue K,et al.Cell-laden hydrogels for osteochondral and cartilage tissue engineering.Acta Biomater.2017;57:1-25.
[26]Huang H,Zhang X,Hu X,et al.Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering.Biomed Mater.2014;9(3):035008.
[27]Lu TJ,Chiu FY,Chiu HY,et al.Chondrogenic Differentiation of Mesenchymal Stem Cells in Three-Dimensional Chitosan Film Culture.Cell Transplant.2017;26(3):417-427.
[28]Zhu Y,Song K,Jiang S,et al.Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor.Appl Biochem Biotechnol.2017;181(1):250-266.
[29]林涛.壳聚糖水凝胶复合脂肪间充质干细胞修复兔关节软骨缺损[J].中华创伤杂志,2016,32(4):357-362.
[30]Madry H,Rey-Rico A,Venkatesan JK,et al.Transforming growth factor Beta-releasing scaffolds for cartilage tissue engineering.Tissue Eng Part B Rev.2014;20(2):106-125.
[31]Yang YH,Barabino GA.Differential morphology and homogeneity of tissue-engineered cartilage in hydrodynamic cultivation with transient exposure to insulin-like growth factor-1 and transforming growth factor-β1.Tissue Eng Part A.2013;19(21-22):2349-2360.
[32]Madry H,Kaul G,Zurakowski D,et al.Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.Eur Cell Mater.2013;25:229-247.
[33]Kessler MW,Grande DA.Tissue engineering and cartilage.Organogenesis.2008;4(1):28-32.
[34]Sporn MB,Roberts AB,Wakefield LM,et al.Transforming growth factor-beta:biological function and chemical structure.Science.1986;233(4763):532-453.
[35]Ahsan SM,Thomas M,Reddy KK,et al.Chitosan as biomaterial in drug delivery and tissue engineering.Int J Biol Macromol.2018;110:97-109.
[36]Merlin Rajesh Lal LP,Suraishkumar GK,Nair PD.Chitosan-agarose scaffolds supports chondrogenesis of Human Wharton's Jelly mesenchymal stem cells.J Biomed Mater Res A.2017;105(7):1845-1855.
[37]Shen J,Gao Q,Zhang Y,et al.Autologous platelet?rich plasma promotes proliferation and chondrogenic differentiation of adipose?derived stem cells.Mol Med Rep.2015;11(2):1298-1303.
[38]Krüger JP,Ketzmar AK,Endres M,et al.Human platelet-rich plasma induces chondrogenic differentiation of subchondral progenitor cells in polyglycolic acid-hyaluronan scaffolds.JBiomed Mater Res B Appl Biomater.2014;102(4):681-692.
[39]Sadeghi-Ataabadi M,Mostafavi-Pour Z,Vojdani Z,et al.Fabrication and characterization of platelet-rich plasma scaffolds for tissue engineering applications.Mater Sci Eng CMater Biol Appl.2017;71:372-380.
[40]Sancho-Tello M,Martorell S,Mata Roig M,et al.Human platelet-rich plasma improves the nesting and differentiation of human chondrocytes cultured in stabilized porous chitosan scaffolds.J Tissue Eng.2017;8:2041731417697545.
[41]赵荣兰,左爱军,梁东春,等.CS/igf-1基因复合物促骨髓基质细胞增殖及分化的研究[J].天津医药,2008,36(1):35-37.
[42]赵荣兰,任玉平,孙蓓,等.壳聚糖转染胰岛素样生长因子基因促进兔关节软骨损伤修复的实验研究[J].中国修复重建外科杂志,2010,24(11):1372-1375.
[43]赵荣兰,彭效祥,楚海荣,等.可磷酸化短肽偶联壳聚糖介导兔关节软骨损伤修复的基因治疗[J].中国修复重建外科杂志,2014,28(11):1346-52.
[44]赵荣兰,彭效祥,宋伟,等.可磷酸化短肽偶联壳聚糖介导IGF-1和IL-1RA双基因联合治疗兔关节软骨损伤[J].中国生物化学与分子生物学报,2015,31(2):175-181.
[45]Kiyotake EA,Beck EC,Detamore MS.Cartilage extracellular matrix as a biomaterial for cartilage regeneration.Ann N YAcad Sci.2016;1383(1):139-159.
[46]Sivandzade F,Mashayekhan S.Design and fabrication of injectable microcarriers composed of acellular cartilage matrix and chitosan.J Biomater Sci Polym Ed.2018;29(6):683-700.
[47]Medeiros Borsagli FGL,Carvalho IC,Mansur HS.Amino acid-grafted and N-acylated chitosan thiomers:Construction of 3D bio-scaffolds for potential cartilage repair applications.Int J Biol Macromol.2018;114:270-282.
[48]Reed S,Lau G,Delattre B,et al.Macro-and micro-designed chitosan-alginate scaffold architecture by three-dimensional printing and directional freezing.Biofabrication.2016;8(1):015003.
[49]Wang X,Wei C,Cao B,et al.Fabrication of Multiple-Layered Hydrogel Scaffolds with Elaborate Structure and Good Mechanical Properties via 3D Printing and Ionic Reinforcement.ACS Appl Mater Interfaces.2018;10(21):18338-18350.
[2]Oryan A,Sahvieh S.Effectiveness of chitosan scaffold in skin,bone and cartilage healing.Int J Biol Macromol.2017;104(Pt A):1003-1011.
[3]徐敬,赵建宁,徐海栋,等.壳聚糖及其衍生物在软骨组织工程中的应用[J].中国组织工程研究,2015,19(25):4081-4085.
[4]陈道玉,张中民,姜丽丽.壳聚糖支架材料在组织工程中的应用与未来[J].中国组织工程研究,2017,21(30):4893-900.
[5]Ali A,Ahmed S.A review on chitosan and its nanocomposites in drug delivery.Int J Biol Macromol.2018;109:273-286.
[6]Rodríguez-Vázquez M,Vega-Ruiz B,Ramos-Zú?iga R,et al.Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine.Biomed Res Int.2015;2015:821279.
[7]Radhakrishnan J,Subramanian A,Krishnan UM,et al.Injectable and 3D Bioprinted Polysaccharide Hydrogels:From Cartilage to Osteochondral Tissue Engineering.Biomacromolecules.2017;18(1):1-26.
[8]Nukavarapu SP,Dorcemus DL.Osteochondral tissue engineering:current strategies and challenges.Biotechnol Adv.2013;31(5):706-721.
[9]Ahmed S,Annu,Ali A,et al.A review on chitosan centred scaffolds and their applications in tissue engineering.Int J Biol Macromol.2018;116:849-862.
[10]傅月荷,吕青.生物来源水凝胶在组织工程中的应用与进展[J].中国修复重建外科杂志,2014,28(8):1030-1036.
[11]Chenite A,Chaput C,Wang D,et al.Novel injectable neutral solutions of chitosan form biodegradable gels in situ.Biomaterials.2000;21(21):2155-2161.
[12]康肸,邓爱鹏,杨树林.壳聚糖基温敏水凝胶的研究进展[J].中国生物工程杂志,2018,38(5):79-84.
[13]Wu J,Liu J,Shi Y,et al.Rheological,mechanical and degradable properties of injectable chitosan/silk fibroin/hydroxyapatite/glycerophosphate hydrogels.J Mech Behav Biomed Mater.2016;64:161-172.
[14]Song K,Li L,Yan X,et al.Characterization of human adipose tissue-derived stem cells in vitro culture and in vivo differentiation in a temperature-sensitive chitosan/β-glycerophosphate/collagen hybrid hydrogel.Mater Sci Eng CMater Biol Appl.2017;70(Pt 1):231-240.
[15]Deng A,Kang X,Zhang J,et al.Enhanced gelation of chitosan/β-sodium glycerophosphate thermosensitive hydrogel with sodium bicarbonate and biocompatibility evaluated.Mater Sci Eng C Mater Biol Appl.2017;78:1147-1154.
[16]Su JY,Chen SH,Chen YP,et al.Evaluation of Magnetic Nanoparticle-Labeled Chondrocytes Cultivated on a Type Ⅱ Collagen-Chitosan/Poly(Lactic-co-Glycolic)Acid Biphasic Scaffold.Int J Mol Sci.2017;18(1).pii:E87.doi:10.3390/ijms18010087.
[17]Chen Z,Zhao M,Liu K,et al.Novel chitosan hydrogel formed by ethylene glycol chitosan,1,6-diisocyanatohexan and polyethylene glycol-400 for tissue engineering scaffold:in vitro and in vivo evaluation.J Mater Sci Mater Med.2014;25(8):1903-1913.
[18]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.JZhejiang Univ Sci B.2015;16(11):914-923.
[19]Oussedik S,Tsitskaris K,Parker D.Treatment of articular cartilage lesions of the knee by microfracture or autologous chondrocyte implantation:a systematic review.Arthroscopy.2015;31(4):732-744.
[20]Man Z,Hu X,Liu Z,et al.Transplantation of allogenic chondrocytes with chitosan hydrogel-demineralized bone matrix hybrid scaffold to repair rabbit cartilage injury.Biomaterials.2016;108:157-167.
[21]Song K,Li L,Yan X,et al.Fabrication and development of artificial osteochondral constructs based on cancellous bone/hydrogel hybrid scaffold.J Mater Sci Mater Med.2016;27(6):114.
[22]刘相杰,宋科官.生物支架材料及间充质干细胞在骨组织工程中的研究与应用[J].中国组织工程研究,2018,22(10):1618-24.
[23]Dai R,Wang Z,Samanipour R,et al.Adipose-Derived Stem Cells for Tissue Engineering and Regenerative Medicine Applications.Stem Cells Int.2016;2016:6737345.
[24]Tamaddon M,Burrows M,Ferreira SA,et al.Monomeric,porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro.Sci Rep.2017;7:43519.
[25]Yang J,Zhang YS,Yue K,et al.Cell-laden hydrogels for osteochondral and cartilage tissue engineering.Acta Biomater.2017;57:1-25.
[26]Huang H,Zhang X,Hu X,et al.Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering.Biomed Mater.2014;9(3):035008.
[27]Lu TJ,Chiu FY,Chiu HY,et al.Chondrogenic Differentiation of Mesenchymal Stem Cells in Three-Dimensional Chitosan Film Culture.Cell Transplant.2017;26(3):417-427.
[28]Zhu Y,Song K,Jiang S,et al.Numerical Simulation of Mass Transfer and Three-Dimensional Fabrication of Tissue-Engineered Cartilages Based on Chitosan/Gelatin Hybrid Hydrogel Scaffold in a Rotating Bioreactor.Appl Biochem Biotechnol.2017;181(1):250-266.
[29]林涛.壳聚糖水凝胶复合脂肪间充质干细胞修复兔关节软骨缺损[J].中华创伤杂志,2016,32(4):357-362.
[30]Madry H,Rey-Rico A,Venkatesan JK,et al.Transforming growth factor Beta-releasing scaffolds for cartilage tissue engineering.Tissue Eng Part B Rev.2014;20(2):106-125.
[31]Yang YH,Barabino GA.Differential morphology and homogeneity of tissue-engineered cartilage in hydrodynamic cultivation with transient exposure to insulin-like growth factor-1 and transforming growth factor-β1.Tissue Eng Part A.2013;19(21-22):2349-2360.
[32]Madry H,Kaul G,Zurakowski D,et al.Cartilage constructs engineered from chondrocytes overexpressing IGF-I improve the repair of osteochondral defects in a rabbit model.Eur Cell Mater.2013;25:229-247.
[33]Kessler MW,Grande DA.Tissue engineering and cartilage.Organogenesis.2008;4(1):28-32.
[34]Sporn MB,Roberts AB,Wakefield LM,et al.Transforming growth factor-beta:biological function and chemical structure.Science.1986;233(4763):532-453.
[35]Ahsan SM,Thomas M,Reddy KK,et al.Chitosan as biomaterial in drug delivery and tissue engineering.Int J Biol Macromol.2018;110:97-109.
[36]Merlin Rajesh Lal LP,Suraishkumar GK,Nair PD.Chitosan-agarose scaffolds supports chondrogenesis of Human Wharton's Jelly mesenchymal stem cells.J Biomed Mater Res A.2017;105(7):1845-1855.
[37]Shen J,Gao Q,Zhang Y,et al.Autologous platelet?rich plasma promotes proliferation and chondrogenic differentiation of adipose?derived stem cells.Mol Med Rep.2015;11(2):1298-1303.
[38]Krüger JP,Ketzmar AK,Endres M,et al.Human platelet-rich plasma induces chondrogenic differentiation of subchondral progenitor cells in polyglycolic acid-hyaluronan scaffolds.JBiomed Mater Res B Appl Biomater.2014;102(4):681-692.
[39]Sadeghi-Ataabadi M,Mostafavi-Pour Z,Vojdani Z,et al.Fabrication and characterization of platelet-rich plasma scaffolds for tissue engineering applications.Mater Sci Eng CMater Biol Appl.2017;71:372-380.
[40]Sancho-Tello M,Martorell S,Mata Roig M,et al.Human platelet-rich plasma improves the nesting and differentiation of human chondrocytes cultured in stabilized porous chitosan scaffolds.J Tissue Eng.2017;8:2041731417697545.
[41]赵荣兰,左爱军,梁东春,等.CS/igf-1基因复合物促骨髓基质细胞增殖及分化的研究[J].天津医药,2008,36(1):35-37.
[42]赵荣兰,任玉平,孙蓓,等.壳聚糖转染胰岛素样生长因子基因促进兔关节软骨损伤修复的实验研究[J].中国修复重建外科杂志,2010,24(11):1372-1375.
[43]赵荣兰,彭效祥,楚海荣,等.可磷酸化短肽偶联壳聚糖介导兔关节软骨损伤修复的基因治疗[J].中国修复重建外科杂志,2014,28(11):1346-52.
[44]赵荣兰,彭效祥,宋伟,等.可磷酸化短肽偶联壳聚糖介导IGF-1和IL-1RA双基因联合治疗兔关节软骨损伤[J].中国生物化学与分子生物学报,2015,31(2):175-181.
[45]Kiyotake EA,Beck EC,Detamore MS.Cartilage extracellular matrix as a biomaterial for cartilage regeneration.Ann N YAcad Sci.2016;1383(1):139-159.
[46]Sivandzade F,Mashayekhan S.Design and fabrication of injectable microcarriers composed of acellular cartilage matrix and chitosan.J Biomater Sci Polym Ed.2018;29(6):683-700.
[47]Medeiros Borsagli FGL,Carvalho IC,Mansur HS.Amino acid-grafted and N-acylated chitosan thiomers:Construction of 3D bio-scaffolds for potential cartilage repair applications.Int J Biol Macromol.2018;114:270-282.
[48]Reed S,Lau G,Delattre B,et al.Macro-and micro-designed chitosan-alginate scaffold architecture by three-dimensional printing and directional freezing.Biofabrication.2016;8(1):015003.
[49]Wang X,Wei C,Cao B,et al.Fabrication of Multiple-Layered Hydrogel Scaffolds with Elaborate Structure and Good Mechanical Properties via 3D Printing and Ionic Reinforcement.ACS Appl Mater Interfaces.2018;10(21):18338-18350.