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Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation

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Abstract

Gelatin is a very promising matrix material for in vitro cell culture and tissue engineering, e.g. due to its native RGD content. For the generation of medical soft tissue implants chemical modification of gelatin improves the mechanical properties of gelatin hydrogels and the viscous behavior of gelatin solutions for liquid handling. We present a systematic study on the influence of high degrees of methacrylation on the properties of gelatin solutions and photo-chemically crosslinked hydrogels. Changes from shear thinning to shear thickening behavior of gelatin solutions were observed depending on mass fraction and degree of methacrylation. Degrees of swelling of crosslinked hydrogels ranged from 194 to 770 % and storage moduli G′ from 368 to 5 kPa, comparable to various natural tissues including several types of cartilage. Crosslinked gels proofed to be cytocompatible according to extract testings based on DIN ISO 10933-5 and in contact with porcine chondrocytes.

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References

  1. Liu Y, Chan-Park MB. Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering. Biomaterials. 2009;30:196–207.

    Article  Google Scholar 

  2. Tseng CL, Wu SYH, Wang WH, Peng CL, Lin FH, Lin CC, Young TH, Shieh MJ. Targeting efficiency and biodistribution of biotinylated-EGF-conjugated gelatin nanoparticles administered via aerosol delivery in nude mice with lung cancer. Biomaterials. 2008;29:3014–22.

    Article  CAS  Google Scholar 

  3. Draye J-P, Delaey B, Van de Voorde A, Van Den Bulcke A, De Reu B, Schacht E. In vitro and in vivo biocompatibility of dextran dialdehyde cross-linked gelatin hydrogel films. Biomaterials. 1998;19:1677–87.

    Article  CAS  Google Scholar 

  4. Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH. Structural and rheological properties of methacrylamide modified gelatin hydrogels. Biomacromolecules. 2000;1:31–8.

    Article  Google Scholar 

  5. Bigi A, Cojazzi G, Panzavolta S, Rubini K, Roveri N. Mechanical and thermal properties of gelatin films at different degrees of glutaraldehyde crosslinking. Biomaterials. 2001;22:763–8.

    Article  CAS  Google Scholar 

  6. Marois Y, Chakfé N, Deng X, Marois M, How T, King MW, Guidoin R. Carbodiimide cross-linked gelatin: a new coating for porous polyester arterial prostheses. Biomaterials. 1995;16:1131–9.

    Article  CAS  Google Scholar 

  7. Fukaya C, Nakayama Y, Murayama Y, Omata S, Ishikawa A, Hosaka Y, Nakagawa T. Improvement of hydrogelation abilities and handling of photocurable gelatin-based crosslinking materials. J Biomed Mater Res B. 2009;91B:329–36.

    Article  CAS  Google Scholar 

  8. Nickerson MT, Patel J, Heyd DV, Rousseau D, Paulson AT. Kinetic and mechanistic considerations in the gelation of genipin-crosslinked gelatin. Int J Biol Macromol. 2006;39:298–302.

    Article  CAS  Google Scholar 

  9. Tronci G, Neffe AT, Pierce BF, Lendlein A. An entropy—elastic gelatin-based hydrogel system. J Mater Chem. 2010;20:8875–84.

    Article  CAS  Google Scholar 

  10. Barbetta A, Massimi M, Conti Devirgiliis L, Dentini M. Enzymatic cross-linking versus radical polymerization in the preparation of gelatin polyHIPEs and their performance as scaffolds in the culture of hepatocytes. Biomacromolecules. 2006;7:3059–68.

    Article  CAS  Google Scholar 

  11. Fuchsbauer HL, Gerber U, Engelmann J, Seeger T, Sinks C, Hecht T. Influence of gelatin matrices cross-linked with transglutaminase on the properties of an enclosed bioactive material using [beta]-galactosidase as model system. Biomaterials. 1996;17:1481–8.

    Article  CAS  Google Scholar 

  12. Möller S, Weisser J, Bischoff S, Schnabelrauch M. Dextran and hyaluronan methacrylate based hydrogels as matrices for soft tissue reconstruction. Biomol Eng. 2007;24:496–504.

    Article  Google Scholar 

  13. van Dijk-Wolthuis W, Franssen O, Talsma H, van Steenbergen M, Kettenes van den Bosch J and Hennink W. Synthesis, characterization and polymerization of glycidyl methacrylate derivatized dextran. Macromolecules. 1995;28:6317–6322.

    Google Scholar 

  14. Schnabelrauch M, Vogt S, Larchers Y, Wilke I. Biodegradable polymer networks based on oligolactide macromers: synthesis, properties and biomedical applications. Biomol Eng. 2002;19:295–8.

    Article  CAS  Google Scholar 

  15. Martineau L, Peng H and Shek P. Development of a novel biomaterial: part II: evaluation of a photo-crosslinking method. Defence R&D Canada DRDC 2005-201.

  16. Hu X, Ma L, Wang C, Gao C. Gelatin hydrogel prepared by photo-initiated polymerization and loaded with TGF-b1 for cartilage tissue engineering. Macromol Biosci. 2009;9:1194–201.

    Article  CAS  Google Scholar 

  17. Erkamp RQ, Wiggins P, Skovoroda AR, Emelianov SY, O’Donnell M. Measuring the elastic modulus of small tissue samples. Ultrason Imaging. 1998;20:17–28.

    CAS  Google Scholar 

  18. Frank EH, Grodzinsky AJ. Cartilage electromechanics-II. A continuum model of cartilage electrokinetics and correlation with experiments. J Biomech. 1987;20:629–39.

    Article  CAS  Google Scholar 

  19. Stockwell R and Meachim G.The matrix. In: M. A. R. Freeman, editors. Adult articular cartilage. London: Pitman Medical; 1979.

  20. Hsu SH, Whu SW, Hsieh SC, Tsai CL, Chen DC, Tan TS. Evaluation of chitosan-alginate-hyaluronate complexes modified by a RGD-containing protein as tissue-engineering scaffolds for cartilage regeneration. Artif Organs. 2004;28:693–703.

    Article  CAS  Google Scholar 

  21. Maher PS, Keatch RP, Donnelly K, Mackay RE. Construction of 3D biological matrices using rapid prototyping technology. Rapid Prototyp J. 2009;15:204–10.

    Article  Google Scholar 

  22. Habeeb AF. Determination of free amino groups in proteins by trinitrobezenesulfonic acid. Anal Biochem. 1966;14:328–36.

    Article  CAS  Google Scholar 

  23. Khademhosseini A, Eng G, Yeh J, Fukuda J, Blumling J, Langer R, Burdick JA. Micromolding of photocrosslinkable hyaluronic acid for cell encapsulation and entrapment. J Biomed Res A. 2006;79(3):522–32.

    Article  Google Scholar 

  24. Fedorovich NE, Oudshoorn MH, van Geemen D, Hennink WE, Alblas J, Dhert WJA. The effect of photopolymerization on stem cells embedded in hydrogels. Biomaterials. 2009;30:344–53.

    Article  CAS  Google Scholar 

  25. Williams CG, Malik AN, Kim TK, Manson PN, Elisseeff JH. Variable cytocompatinility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. Biomaterials. 2005;26:1211–8.

    Article  CAS  Google Scholar 

  26. Bryant SJ, Nuttelman CR, Anseth KS. Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro. J Biomater Sci Polym Ed. 2000;11(5):439–57.

    Article  CAS  Google Scholar 

  27. Mironi-Harpaz I, Wang DY, Venkatraman S, Seliktar D. Photopolymerization of cell-encapsulating hydrogels: crosslining efficiency versus cytotoxicity. Acta Biomater. 2012;8:1838–48.

    Article  CAS  Google Scholar 

  28. Nichol JW, Koshy ST, Bae H, Hwang CM, Yamanlar S, Khademhosseini A. Cell-laden microengineered gelatin methacrylate hydrogels. Biomaterials. 2010;31:5536–44.

    Article  CAS  Google Scholar 

  29. Cheftel J-C, Cuq J-L, Lorient D, Reimerdes E. Lebensmittelproteine: Biochemie, funktionelle Eigenschaften, Ernährungsphysiologie, chemische Modifizierung. Hamburg: Behr’s Verlag und Co.; 1992.

    Google Scholar 

  30. Schrieber R, Gareis H. Gelatine handbook: theory and industrial practice. Weinheim: Wiley-VCH Verlag; 2007.

    Google Scholar 

  31. Witten TA, Cohen MH. Cross-linking in shear-thickening ionomers. Macromolecules. 1985;18:1915–8.

    Article  CAS  Google Scholar 

  32. Aamer KA, Sardinha H, Bhatia SR, Tew GN. Rheological studies of PLLA-PEO-PLLA triblock copolymer hydrogels. Biomaterials. 2004;25:1087–93.

    Article  CAS  Google Scholar 

  33. Fujiwara T, Mukose T, Yamaoka T, Yamane H, Sakurai S, Kimura Y. Novel thermo-responsive formation of a hydrogel by stereo-complexation between PLLA-PEG-PLLA and PDLA-PEG-PDLA block copolymers. Macromol Biosci. 2001;1:204–8.

    Article  CAS  Google Scholar 

  34. Vanderhooft JL, Alcoutlabi M, Magda JJ, Prestwich GD. Rheological properties of cross-linked hyaluronan-gelatin hydrogels for tissue engineering. Macromol Biosci. 2009;9:20–8.

    Article  CAS  Google Scholar 

  35. Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell. 2006;126:677–89.

    Article  CAS  Google Scholar 

  36. Kim S, English AE, Kihm KD. Surface elasticity and charge concentration-dependent endothelial cell attachment to copolymer polyelectrolyte hydrogel. Acta Biomater. 2009;5:144–51.

    Article  CAS  Google Scholar 

  37. Kim B-S, Mooney DJ. Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 1998;16:224–30.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors thank Sarah Queck (IGVT, University of Stuttgart) for rheological measurements on gelatin solutions, Birgit Claasen (Institute of Organic Chemistry, University of Stuttgart) for the NMR measurements, Markus Schandar (Fraunhofer IGB, Stuttgart) for helpful scientific discussions, Martin Schenk (University of Tübingen) for the preparation of the pigs, and Veronika Schönhaar (IGVT, University of Stuttgart) for proof reading of the manuscript. The authors thank the Fraunhofer Gesellschaft (München), Christian Schuh thanks the Peter und Traudl Engelhorn-Stiftung (Weilheim), and Eva Hoch thanks the Max Buchner-Stiftung (Frankfurt) for financial support.

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Correspondence to Günter E. M. Tovar or Kirsten Borchers.

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Hoch, E., Schuh, C., Hirth, T. et al. Stiff gelatin hydrogels can be photo-chemically synthesized from low viscous gelatin solutions using molecularly functionalized gelatin with a high degree of methacrylation. J Mater Sci: Mater Med 23, 2607–2617 (2012). https://doi.org/10.1007/s10856-012-4731-2

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  • DOI: https://doi.org/10.1007/s10856-012-4731-2

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