Injectable hydrogels are widely employed as biomaterials for biomedical applications. In this study, disulfide-containing dextran-phloretic acid conjugates (Dex-SS-PA) are synthesized. In the presence of horseradish peroxidase, Dex-SS-PA solutions gelate to form bioreducible dextran-based hydrogels via the enzymatic crosslinking method. Physical and chemical properties of the hydrogels including gelation time, gel content and degradation properties are investigated. Live-dead assay and methyl thiazolyl tetrazolium assay are used to evaluate biocompatibility of the Dex-SS-PA hydrogels. It is shown that the higher the dextran molecular weight, degree of substitution of phloretic acid moieties and polymer concentrations, the shorter gelation time and the higher gel content of the hydrogels can be obtained. Besides, the Dex-SS-PA hydrogels are degradable under a bioreducible environment. Cellular viability of NIH 3T3 cells incorporated in the Dex-SS-PA hydrogels demonstrated that they reveal low cytotoxicity. The results indicate that the Dex-SS-PA hydrogels are potentially
useful in biomedical applications.
JI Xiao-jun, CAO Ao-neng, JIN Rong
. Bioreduction-Responsive, Enzymatically Crosslinked Injectable Hydrogels[J]. Journal of Shanghai University, 2013
, 19(5)
: 485
-492
.
DOI: 10.3969/j.issn.1007-2861.2013.05.009
[1] Hennink W E, van Nostrum C F. Novel crosslinking methods to design hydrogels [J]. Advanced Drug Delivery Reviews, 2002, 54(1): 13-36.
[2] van Tomme S R, Storm G, Hennink W E. In situ gelling hydrogels for pharmaceutical and biomedical applications [J]. International Journal of Pharmaceutics,
2008, 355(1/2): 1-18.
[3] Bryant S J, Nuttelman C R, Anseth K S. Cytocompatibility of uv and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro [J]. Journal of Biomaterials Science: Polymer Edition, 2000, 11(5): 439-457.
[4] Hienstra C, Zhow W, Zhong Z, et al. Rapidly in situ forming biodegradable robust hydrogels by combining stereocomplexation and photopolymerization [J]. Journal of the American Chemical Society, 2007, 129(32): 9918-9926.
[5] Lukaszczyk J, Smiga M, Jaszcz K, et al. Evaluation of oligo (ethylene glycol) dimethacrylates effects on the properties of new biodegradable bone cement compositions [J]. Macromolecular Bioscience, 2005, 5(1): 64-69.
[6] Kobayashi S, Uyama H, Kimura S. Enzymatic polymerization [J]. Chemical Reviews, 2001, 101(12): 3793-3818.
[7] Jin R, Hiemstra C, Zhong Z, et al. Enzymemediated fast in situ formation of hydrogels from dextran-tyramine conjugates [J]. Biomaterials, 2007, 28(18): 2791-2800.
[8] Jin R, Teixeira L S M, Dijsktra P J, et al. Enzymatically crosslinked dextran-tyramine hydrogels asinjectable scaffolds for cartilage tissue engineering [J]. Tissue Eng: Part A, 2010, 16(8): 2429-2440.
[9] Zugates G T, Anderson D G, Little S R, et al. Synthesis of poly (amino ester)s with thiol-reactive side chains for DNA delivery [J]. Journal of the American Chemical Society, 2006, 128(39): 12726-12734.
[10] Ramirez J, Sanchez-chaves M, Arranz F. Dextran functionalized by 4-nitrophenyl carbonate groups. Aminolysis reactions [J]. Die Angewandte Makromolekulare Chemie, 1995, 225(1): 123-130.
[11] Ellman G L. A colorimetric method for determining low concentrations of mercaptans [J]. Archives of biochemistry and biophysics, 1958, 74(2): 443-450.
[12] Fukuoka T, Uyama H, Kobayashi S. Polymerization of polyfunctional macromolecules: synthesis of a new class of high molecular weight poly (amino acid)s by oxidative coupling of phenol-containing precursor polymers [J]. Biomacromolecules, 2005, 5(3): 977-983.
