title: An Injectable Enzymatically Crosslinked Carboxymethylated Pullulan/Chondroitin Sulfate Hydrogel for Cartilage Tissue Engineering.
abstract: In this study, an enzymatically cross-linked injectable and biodegradable hydrogel system comprising carboxymethyl pullulan-tyramine (CMP-TA) and chondroitin sulfate-tyramine (CS-TA) conjugates was successfully developed under physiological conditions in the presence of both horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) for cartilage tissue engineering (CTTE). The HRP crosslinking method makes this injectable system feasible, minimally invasive and easily translatable for regenerative medicine applications. The physicochemical properties of the mechanically stable hydrogel system can be modulated by varying the weight ratio and concentration of polymer as well as the concentrations of crosslinking reagents. Additionally, the cellular behaviour of porcine auricular chondrocytes encapsulated into CMP-TA/CS-TA hydrogels demonstrates that the hydrogel system has a good cyto-compatibility. Specifically, compared to the CMP-TA hydrogel, these CMP-TA/CS-TA composite hydrogels have enhanced cell proliferation and increased cartilaginous ECM deposition, which significantly facilitate chondrogenesis. Furthermore, histological analysis indicates that the hydrogel system exhibits acceptable tissue compatibility by using a mouse subcutaneous implantation model. Overall, the novel injectable pullulan/chondroitin sulfate composite hydrogels presented here are expected to be useful biomaterial scaffold for regenerating cartilage tissue.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Songrui
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, P. R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Yunzhou
authors.initials: Y
authors.lastname: Ni
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Yu
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Su
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, P. R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.|Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, P. R. China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P. R. China.|Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Jiangsu Key Laboratory of Biomedical Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210046, P. R. China.
authors.forename: Deyue
authors.initials: D
authors.lastname: Yan
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002356:Cartilage / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism; D020219:Chondrogenesis; D002809:Chondroitin Sulfates / Q000737:chemistry; D005936:Glucans / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000138:chemical synthesis / Q000737:chemistry; D012038:Regeneration; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D005936:Glucans; C410955:carboxymethylpullulan; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D002809:Chondroitin Sulfates
references.citation: Biomacromolecules. 2012 Mar 12;13(3):604-11
references.pmid: 22263670
references.citation: Carbohydr Polym. 2015 Jun 5;123:190-207
references.pmid: 25843851
references.citation: Acta Biomater. 2010 Sep;6(9):3640-8
references.pmid: 20215057
references.citation: Osteoarthritis Cartilage. 2000 Sep;8(5):309-34
references.pmid: 10966838
references.citation: Sci Rep. 2015 May 11;5:9879
references.pmid: 25961959
references.citation: Adv Mater. 2013 Oct 4;25(37):5257-86
references.pmid: 24038153
references.citation: Matrix Biol. 2010 Jan;29(1):51-62
references.pmid: 19720146
references.citation: Biomaterials. 2014 Apr;35(12):3873-84
references.pmid: 24485791
references.citation: Acta Biomater. 2014 Jan;10(1):214-23
references.pmid: 24140603
references.citation: Nat Mater. 2007 May;6(5):385-92
references.pmid: 17435762
references.citation: Tissue Eng Part A. 2010 Aug;16(8):2429-40
references.pmid: 20214454
references.citation: Acta Biomater. 2014 Aug;10(8):3650-63
references.pmid: 24811827
references.citation: J Control Release. 2002 Sep 18;83(1):41-51
references.pmid: 12220837
references.citation: Chem Rev. 2011 Aug 10;111(8):4453-74
references.pmid: 21417222
references.citation: Biomacromolecules. 2010 Mar 8;11(3):706-12
references.pmid: 20121075
references.citation: Tissue Eng Part A. 2015 Mar;21(5-6):861-74
references.pmid: 25333855
references.citation: Biomacromolecules. 2013 Feb 11;14(2):413-23
references.pmid: 23259935
references.citation: J Control Release. 2013 Oct 28;171(2):143-51
references.pmid: 23880471
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):10012-7
references.pmid: 22665791
references.citation: Biomaterials. 2012 Jan;33(1):80-90
references.pmid: 21963148
references.citation: Matrix Biol. 2008 Jan;27(1):12-21
references.pmid: 17689060
references.citation: Soft Matter. 2008 Mar 20;4(4):880-887
references.pmid: 32907194
references.citation: J Control Release. 2011 May 30;152(1):186-95
references.pmid: 21291927
references.citation: Tissue Eng Part A. 2009 Oct;15(10):3037-48
references.pmid: 19331581
references.citation: Adv Healthc Mater. 2013 Jan;2(1):57-71
references.pmid: 23184739
references.citation: Tissue Eng Part A. 2011 Mar;17(5-6):631-44
references.pmid: 20919949
references.citation: Chem Soc Rev. 2012 Mar 21;41(6):2193-221
references.pmid: 22116474
references.citation: Biomaterials. 2015 May;51:238-249
references.pmid: 25771014
references.citation: Biomaterials. 2013 Jul;34(21):5007-18
references.pmid: 23570717
references.citation: Acta Biomater. 2013 Jan;9(1):4609-17
references.pmid: 22963851
references.citation: Sci Rep. 2014 Jan 15;4:3701
references.pmid: 24424429
references.citation: Tissue Eng Part A. 2013 Jun;19(11-12):1349-59
references.pmid: 23379843
references.citation: Biomaterials. 2012 Feb;33(5):1281-90
references.pmid: 22118821
references.citation: Biomaterials. 2013 Dec;34(37):9430-40
references.pmid: 24050877
references.citation: PLoS One. 2014 Oct 20;9(10):e110251
references.pmid: 25330002
references.citation: Macromol Biosci. 2012 Mar;12(3):395-401
references.pmid: 22223225
references.citation: Acta Biomater. 2009 Jul;5(6):1937-47
references.pmid: 19282262
references.citation: Acta Biomater. 2005 Mar;1(2):243-52
references.pmid: 16701801
references.citation: Tissue Eng Part A. 2012 Jan;18(1-2):35-44
references.pmid: 21770864
references.citation: Biomaterials. 2012 Apr;33(11):3164-74
references.pmid: 22265787
references.citation: Macromol Biosci. 2012 Jul;12(7):901-10
references.pmid: 22696505
references.citation: Soft Matter. 2011 Jan 1;7(5):1903-1911
references.pmid: 21415929
references.citation: Biomaterials. 2014 Feb;35(7):2207-17
references.pmid: 24333028
references.citation: Biomacromolecules. 2007 Apr;8(4):1109-15
references.pmid: 17358076
references.citation: Biomaterials. 2010 Apr;31(11):3103-13
references.pmid: 20116847
references.citation: Tissue Eng Part A. 2014 Feb;20(3-4):819-29
references.pmid: 24070233
references.citation: Stem Cell Res Ther. 2015 Mar 19;6:34
references.pmid: 25889571