Abstract
For the requirement of preliminary vascularization, the scaffolds for thick tissue engineering should possess not only good cell affinity, but also anticoagulant ability. In this paper, an enzymatically crosslinked hydrogel scaffold based on sulfated chitosan (SCTS) was prepared. Firstly, sulfated chitosan-hydroxyphenylpionic acid (SCTS-HPA) conjugate was synthesized, and its structure was identified by FITR and 1H NMR. And then an enzymatically crosslinked hydrogel was prepared in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation time, mechanical property, morphology and cytotoxicity to human umbilical vein endothelial cells (HUVECs) of the hydrogel was evaluated in vitro, the tissue compatibility of SCTS scaffold was studied in vivo. The results showed that the gelation time, mechanical property, morphology of the dehydrated hydrogel could be controlled by the HRP and H2O2 concentration. The cytotoxicity test showed that the hydrogel extracts had no cytotoxicity to HUVECs. The in vivo assay indicated that SCTS-HPA scaffold showed good tissue compatibility, and no thrombus formation. All these results indicated that the SCTS-HPA scaffold could be used as thick tissue engineering scaffold.
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Jain RK, Au P, Tam J, Duda DG, Fukumura D. Engineering vascularized tissue. Nat Biotechnol, 2005, 23: 821–823
Singh DK, Ray AR. Biomedical applications of chitin, chitosan, and their derivatives. J Macromol Sci. Part C: Polymer Reviews, 2000, 40: 69–83
Amiji MM. Surface modification of chitosan membranes by complexation-interpenetration of anionic polysaccharides for improved blood compatibility in hemodialysis. J Biomater Sci Polym Ed, 1996, 8: 281–98
Chen XG, Park HJ. Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions. Carbohyd Polym, 2003, 53: 355–359
Davis SS, Lin W, Bignotti Fabio, Ferruti P. Conjugate of polyethylene glycol and chitosan. United State Patent, US 6730735 B2, 2004-05-04
Jayakumar R, New N, Tokura S, Tamura H. Sulfated chitin and chitosan as novel biomaterials. Int J Biol Macromol, 2007, 40: 175–181
Mariappan MR, Alas EA, Williams JG, Prager MD. Chitosan and chitosan sulfated have opposing effects on collagen-fibroblast interactions. Wound Repair Regen, 1999, 7: 400–406
Li QL, Huang N, Chen JL, Chen C, Chen JY. Endothelial cell and platelet behavior on titanium modified with a mutilayer of polyelectrolytes. J Bioact Compat Pol, 2009, 24: 129–150
Terbojevich M, Carraro C, Cosani A. Solution studies of chitosan 6-O-sulfate. Makromol Chem, 1989, 190: 2847–2855
Tian Q, Wang XH, Wang W, Zhang CN, Wang P, Yuan Z. Self-assembly and liver targeting of sulfated chitosan nanoparticles functionalized with glycyrrhetinic acid. Nanomedicine, 2012, 8: 870–879
LeRoux MA, Guilak F, Setton LA. Compressive and shear properties of alginate gel: Effects of sodium ions and alginate concentration. J Biomed Mater Res, 1999, 47: 46–53
Lin RZ, Miao J, Dong SX. Synthesis and Properties of pH-sensitive Sulfated Chitosan(SCS) Hydrogels. J Mater Sci Eng, 2008, 26: 950–953
Park KM, Shin YM, Joung YK, Shin H, Park KD. In situ forming hydrogels based on tyramine conjugated 4-Arm-PPO-PEO via enzymatic oxidative reaction. Biomacromolecules, 2010, 11: 706–712
Lee F, Chung JE, Kurisawa M. An injectable hyaluronic acidtyramine hydrogel system for protein delivery. J Control Release, 2009, 134: 186–193
Kurisawa M, Chung JE, Yang YY, Gao SJ, Uyama H. Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for drug delivery and tissue engineering. Chem Commun, 2005, 14: 4312–4314
Sakai S, Kawakami K. Synthesis and characterization of both ionically and enzymatically cross-linkable alginate. Acta Biomater, 2007, 3: 495–501
Wang LS, Boulaire J, Chan PP, Chung JE, Kurisawa M. The role of stiffness of gelatin-hydroxyphenylpropionic acid hydrogels formed by enzyme-mediated crosslinking on the differentiation of human mesenchymal stem cell. Biomaterials, 2010, 31: 8608–8616
Hirakawa K, Hashizume K, Hayashi T. Viscoelastic property of human brain-for the analysis of impact injury. No To Shinkei, 1981, 33: 1057–1065
Miller K, Chinzei K, Orssengo G, Bednarz P. Mechanical properties of brain tissue in-vivo: Experiment and computer simulation. J Biomech, 2000, 33: 1369–1376
Evans DW, Moran EC, Baptista PM, Soker S, Sparks JL. Scale-dependent mechanical properties of native and decellularized liver tissue. Biomech Model Mechanobiol, 2012, DOI 10.1007/s10237-012-0426-3
Chen F, Tian M, Zhang DM, Wang JY, Wang QG, Yu XX, Zhang XH, Wan CX. Preparation and characterization of oxidized alginate covalently cross-linked galactosylated chitosan scaffold for liver tissue engineering. Mat Sci Eng C-Bio S, 2011, 32: 310–320
Drury JL, Mooney DJ. Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials, 2003, 24: 4337–4351
O’Brien FJ, Harley BA, Yannas IV, Gibson LJ. The effect of pore size on cell adhesion in collagen-GAG scaffolds. Biomaterials, 2005, 26: 433–441
Lee F, Chung JE, Kurisawa M. An injectable enzymatically crosslinked hyaluronic acid-tyramine hydrogel system with independent tuning of mechanical strength and gelation rate. Soft Matter, 2008, 4: 880–887
Rosiak J, Olejniczak J, Pekala W. Fast reaction of irradiated polymers-I. Crosslinking and degradation of polyvinylpyrrolidone. Int J Radiat Appl Instrum C Radiat Phys Chem, 1990, 36: 747–755
Jonas SK, Riley PA, Willson RL. Hydrogel peroxide cytotoxicity. Low-temperature enhancement by ascorbate or reduced lipoate. Biochem J, 1989, 264: 651–655
Novosel EC, Kleinhans C, Kluger PJ. Vascularization is the key challenge in tissue engineering. Adv Drug Deliv Rev, 2011, 63: 300–311
Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA. Perfusion-decellularized matrix: Using nature’s platform to engineer a bioartificial heart. Nat Med, 2008, 14: 213–221
Yu J, Gu Y, Du KT, Miharda S, Sievers RE, Lee RJ. The effect of injected RGD modified alginate on angiogenesis and left ventricular function in a chronic rat infarct model. Biomaterials, 2009, 30: 751–756
Cai K, Kong T, Wang L, Liu P, Yang W, Chen C. Regulation of endothelial cells migration on poly (D, L-lactic acid) films immobilized with collagen gradients. Colloids Surf B Biointerfaces, 2010, 79: 291–297
Li J, Pan J, Zhang L, Yu Y. Culture of hepatocytes on fructose-modified chitosan scaffolds. Biomaterials, 2003, 24: 2317–2322
Fu D, Han B, Dong W, Yang Z, Lv Y, Liu W. Effects of carboxymethyl chitosan on the blood system of rats. Biochem Biophys Res Commun, 2011, 408: 110–114
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Chen, Z., Wang, W., Guo, L. et al. Preparation of enzymatically cross-linked sulfated chitosan hydrogel and its potential application in thick tissue engineering. Sci. China Chem. 56, 1701–1709 (2013). https://doi.org/10.1007/s11426-013-4887-8
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DOI: https://doi.org/10.1007/s11426-013-4887-8