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Synthesis of functionalized-thermo responsive-water soluble co-polymer for conjugation to protein for biomedical applications

Published online by Cambridge University Press:  25 January 2013

Ali Fathi
Affiliation:
School of Chemical and Biomolecular Engineering, the University of Sydney, NSW 2006, Australia
Hua Wei
Affiliation:
School of Chemical and Biomolecular Engineering, the University of Sydney, NSW 2006, Australia
Wojciech Chrzanowski
Affiliation:
Faculty of Pharmacy, the University of Sydney, NSW 2006, Australia,
Anthony S. Weiss
Affiliation:
School of Molecular Bioscience, the University of Sydney, NSW 2006, Australia,
Fariba Dehghani
Affiliation:
School of Chemical and Biomolecular Engineering, the University of Sydney, NSW 2006, Australia
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Abstract

The aim of this study was to develop a thermo-responsive and bioactive polymer with suitable mechanical properties for musculoskeletal tissue engineering applications. A copolymer was synthesized that comprised of hydrophilic polyethylene glycol, thermo responsive N-isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate-poly(lactide) (HEMA-PLA) to enhance mechanical strength and an active N-acryloxysuccinimide (NAS) group for conjugation to proteins to enhance biological properties. A model protein such as elastin was used to assess the feasibility of conjugating this polymer to protein. The results of 1HNMR analyses confirmed that random polymerization was viable technique for synthesis of this copolymer. The co-polymers synthesized with PEG content of 3 mol% were water soluble. A hydrogel was created by dissolving the copolymer and elastin below room temperature in aqueous media, followed by rapid gelation at 37°C. The results of Fourier transform infrared analyses confirmed the conjugation of protein to copolymer due to significant reduction of ester group absorption (1735 cm−1). This data confirmed molecular interaction between protein and the temperature responsive co-polymer. Our preliminary results demonstrated that it is viable to tune different properties of this hydrogel by changing the composition of co-polymer.

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Articles
Copyright
Copyright © Materials Research Society 2013 

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References

REFERENCES

Kulshrestha, A. S., Laredo, W. R., Matalenas, T., Cooper, K. L., Technologies, A., and Llc, R. M., “Cyclic Dithiocarbonates□: Novel in Situ Polymerizing Biomaterials for Medical,“ 2010.CrossRefGoogle Scholar
Annabi, N., Mithieux, S. M., Weiss, A. S., and Dehghani, F., “Cross-linked open-pore elastic hydrogels based on tropoelastin, elastin and high pressure CO2.,” Biomaterials, vol. 31, no. 7, pp. 1655–65, Mar. 2010.CrossRefGoogle ScholarPubMed
Annabi, N., Mithieux, S. M., Weiss, A. S., and Dehghani, F., “The fabrication of elastin-based hydrogels using high pressure CO(2).,” Biomaterials, vol. 30, no. 1, pp. 17, Jan. 2009.CrossRefGoogle Scholar
Annabi, N., Mithieux, S. M., Boughton, E. a, Ruys, A. J., Weiss, A. S., and Dehghani, F., “Synthesis of highly porous crosslinked elastin hydrogels and their interaction with fibroblasts in vitro.,” Biomaterials, vol. 30, no. 27, pp. 4550–7, Sep.2009.CrossRefGoogle ScholarPubMed
Lee, K. Y. and Mooney, D. J., “Hydrogels for Tissue Engineering,” Chemical Reviews, vol. 101, no. 7, pp. 18691880, Jul. 2001.CrossRefGoogle ScholarPubMed
Nuttelman, C. R., Rice, M. a, Rydholm, A. E., Salinas, C. N., Shah, D. N., and Anseth, K. S., “Macromolecular Monomers for the Synthesis of Hydrogel Niches and Their Application in Cell Encapsulation and Tissue Engineering.,” Progress in polymer science, vol. 33, no. 2, pp. 167179, Feb. 2008.CrossRefGoogle ScholarPubMed
Van Tomme, S. R., Storm, G., and Hennink, W. E., “In situ gelling hydrogels for pharmaceutical and biomedical applications.,” International journal of pharmaceutics, vol. 355, no. 1–2, pp. 118, May 2008.CrossRefGoogle ScholarPubMed
Jin, R., Moreira Teixeira, L. S., Dijkstra, P. J., Karperien, M., van Blitterswijk, C. a, Zhong, Z. Y., and Feijen, J., “Injectable chitosan-based hydrogels for cartilage tissue engineering.,” Biomaterials, vol. 30, no. 13, pp. 2544–51, May 2009.CrossRefGoogle ScholarPubMed
Sanchez, J. G. and Tsinman, T., “Thermoresponsive Platforms for Tissue Engineering and Regenerative Medicine,” vol. 57, no. 12, pp. 3249–3258, 2011.Google Scholar
Nettles, D. L., Chilkoti, A., and Setton, L. a, “Applications of elastin-like polypeptides in tissue engineering.,” Advanced drug delivery reviews, vol. 62, no. 15, pp. 1479–85, Dec. 2010.CrossRefGoogle ScholarPubMed
Simnick, A. J., Lim, D. W., Chow, D., and Chilkoti, A., “Biomedical and Biotechnological Applications of Elastin-Like Polypeptides,” Polymer Reviews, vol. 47, no. 1, pp. 121154, Apr. 2007.CrossRefGoogle Scholar
Lim, D. W., Nettles, D. L., Setton, L. a, and Chilkoti, A., “In situ cross-linking of elastin-like polypeptide block copolymers for tissue repair.,” Biomacromolecules, vol. 9, no. 1, pp. 222–30, Jan. 2008.CrossRefGoogle ScholarPubMed
Abe, M., Takahashi, M., Tokura, S., Tamura, H., and Nagano, A., “Cartilage-scaffold composites produced by bioresorbable beta-chitin sponge with cultured rabbit chondrocytes.,” Tissue engineering, vol. 10, no. 3–4, pp. 585–94, 2004.CrossRefGoogle ScholarPubMed
Iwasaki, N., Kasahara, Y., Yamane, S., Igarashi, T., Minami, A., and Nisimura, S., “Chitosan-Based Hyaluronic Acid Hybrid Polymer Fibers as a Scaffold Biomaterial for Cartilage Tissue Engineering,” Polymers, vol. 3, no. 1, pp. 100113, Dec. 2010.CrossRefGoogle Scholar
Guan, J., Hong, Y., Ma, Z., and Wagner, W. R., “Protein-reactive, thermoresponsive copolymers with high flexibility and biodegradability.,” Biomacromolecules, vol. 9, no. 4, pp. 1283–92, Apr. 2008.CrossRefGoogle ScholarPubMed
Neradovic, D., Hinrichs, W. L. J., Kettenes-van den Bosch, J. J., and Hennink, W. E., “Poly(N-isopropylacrylamide) with hydrolyzable lactic acid ester side groups: a new type of thermosensitive polymer,” Macromolecular Rapid Communications, vol. 20, no. 11, pp. 577581, Nov. 1999.3.0.CO;2-D>CrossRefGoogle Scholar
Fitzpatrick, S. D., Jafar Mazumder, M. a, Muirhead, B., and Sheardown, H., “Development of injectable, resorbable drug-releasing copolymer scaffolds for minimally invasive sustained ophthalmic therapeutics.,” Acta biomaterialia, vol. 8, no. 7, pp. 2517–28, Jul. 2012.CrossRefGoogle ScholarPubMed
Annabi, N., Fathi, A., Mithieux, S. M., Weiss, A. S., and Dehghani, F., “Fabrication of porous PCL/elastin composite scaffolds for tissue engineering applications,” The Journal of Supercritical Fluids, vol. 59, pp. 157167, Nov. 2011.CrossRefGoogle Scholar
Annabi, N., Fathi, A., Mithieux, S. M., Martens, P., Weiss, A. S., and Dehghani, F., “The effect of elastin on chondrocyte adhesion and proliferation on poly (□-caprolactone)/elastin composites.,” Biomaterials, vol. 32, no. 6, pp. 1517–25, Feb.2011.CrossRefGoogle Scholar
van Dijk-Wolthuls, W., “A new class of polymerizable dextrans with hydrolyzable groups: hydroxyethyl methacrylated dextran with and without oligolactate spacer,” Polymer, vol. 38, no. 25, pp. 6235–42, 1997.CrossRefGoogle Scholar