Degradable Hydrogels for Tissue Engineering – Part I: Synthesis by RAFT Polymerization and Characterization of PHEMA Containing Enzymatically Degradable Crosslinks

Article Preview

Abstract:

A nonapeptide, which is sensitive to enzymatic digestion by collagenase, was modified by the covalent attachment of an acrylamido group at the terminal positions. The functionalized peptide was used as a crosslinking agent during polymerization of 2-hydroxyethyl methacrylate (HEMA). Reversible addition-fragmentation chain transfer (RAFT) method was used to obtain a polymer (PHEMA) with an average theoretical molecular weight of 4000 Da, containing enzymatically labile peptide crosslinks. The functionalized peptide was analyzed in detail by 1H and 13C nuclear magnetic resonance (NMR) spectrometry. The polymerization reaction was monitored by near infrared spectrometry, while the resulting polymer was analyzed by size exclusion chromatography and solid NMR spectrometry. The peptide-crosslinked PHEMA was subjected to an in-vitro degradation assay in the presence of collagenase. At the highest concentration of enzyme used in the study, a weight loss of 35% was recorded after 60 days of incubation in the collagenolytic medium. This suggests that crosslinking with enzymatically degradable peptides is a valid method for inducing biodegradability in polymers that otherwise are not degradable.

You might also be interested in these eBooks

Info:

Pages:

67-85

Citation:

Online since:

September 2010

Export:

Price:

[1] T. V. Chirila, Y. -C. Chen, B. J. Griffin and I. J. Constable: Polym. Int., Vol. 32 (1993) p.221.

Google Scholar

[2] Y. -C. Chen, T. V. Chirila and A. V. Russo: Mater. Forum, Vol. 17 ( 1993) p.57.

Google Scholar

[3] T. V. Chirila et al.: Biomaterials, Vol. 14 (1993) p.26.

Google Scholar

[4] T. V. Chirila, B. Higgins and P. D. Dalton: Cellular Polym., Vol. 17 (1998) p.141.

Google Scholar

[5] Q. Liu et al.: Biomaterials, Vol. 21 (2000) p.2163.

Google Scholar

[6] T. V. Chirila et al.: J. Biomed. Mater. Res., Vol. 28 (1994) p.745.

Google Scholar

[7] T. V. Chirila et al.: Prog. Polym. Sci., Vol. 23 (1998) p.447.

Google Scholar

[8] T. V. Chirila: Biomaterials, Vol. 22 (2001) p.3311.

Google Scholar

[9] G. J. Crawford et al.: Ophthalmology, Vol. 109 (2002) p.883.

Google Scholar

[10] C. R. Hicks et al.: Eye, Vol. 17 (2003) p.385.

Google Scholar

[11] D. Duan, B. J. Klenkler and H. Sheardown: Expert Rev. Med. Devices, Vol. 3 (2006) p.59.

Google Scholar

[12] C. R. Hicks et al.: Br. J. Ophthalmol., Vol. 83 (1999) p.616.

Google Scholar

[13] C. R. Hicks et al.: Ophthalmic Plast. Reconstr. Surg., Vol. 15 (1999) p.326.

Google Scholar

[14] G. W. Plant, A. R. Harvey and T. V. Chirila: Brain Res., Vol. 671 (1995) p.119.

Google Scholar

[15] G. W. Plant, T. V. Chirila and A. R. Harvey: Cell Transplantation, Vol. 7, (1998) p.381.

Google Scholar

[16] P. D. Dalton and M. S. Shoichet: Biomaterials, Vol. 22 (2001) p.2661.

Google Scholar

[17] P. D. Dalton, L. Flynn and M. S. Shoichet: Biomaterials, Vol. 23 (2002) p.3843.

Google Scholar

[18] L. Flynn, P. D. Dalton and M. S. Shoichet: Biomaterials, Vol. 24 (2003) p.4265.

Google Scholar

[19] E. C. Tsai, P. D. Dalton, M. S. Shoichet and C. H. Tator: Biomaterials, Vol. 27 (2006) p.519.

Google Scholar

[20] M. B. Murphy and A. G. Mikos, in: Principles of Tissue Engineering, 3rd Edn, edited by R. Lanza, R. Langer and J. Vacanti, Elsevier, Amsterdam (2007) p.309.

Google Scholar

[21] K. Ulbrich, E. I. Zacharieva, B. Obereigner and J. Kopeček: Biomaterials, Vol. 1 (1980) p.199.

Google Scholar

[22] P. Rejmanová, B. Obereigner and J. Kopeček: Makromol. Chem., Vol. 182 (1981) p.1899.

DOI: 10.1002/macp.1981.021820703

Google Scholar

[23] J. Kopeček et al.: Makromol. Chem., Vol. 182 (1981) p.2941.

Google Scholar

[24] P. Rejmanová et al.: Makromol. Chem., Vol. 184 (1983) p. (2000).

Google Scholar

[25] V. Šubr, R. Duncan and J. Kopeček: J. Biomater. Sci. Polym. Edn, Vol. 1 (1990) p.261.

Google Scholar

[26] K. Park: Biomaterials, Vol. 9 (1988) p.435.

Google Scholar

[27] W. S. W. Shalaby and K. Park: Pharm. Res., Vol. 7 (1990) p.816.

Google Scholar

[28] W. S. W. Shalaby, W. E. Blevins and K. Park: J. Controlled Rel., Vol. 19 (1992) p.131.

Google Scholar

[29] S. Kim and K. E. Healy: Biomacromolecules, Vol. 4 (2003) p.1214.

Google Scholar

[30] X. He and E. Jabbari: Biomacromolecules, Vol. 8 (2007) p.780.

Google Scholar

[31] J. L. West and J. A. Hubbell: Macromolecules, Vol. 32 (1999) p.710.

Google Scholar

[32] S. Halstenberg et al.: Biomacromolecules, Vol. 3 (2002) p.710.

Google Scholar

[33] M. Saffran et al.: Science, Vol. 233 (1986) p.1081.

Google Scholar

[34] M. Přádný and J. Kopeček: Makromol. Chem., Vol. 191 (1990) p.1887.

Google Scholar

[35] H. Brønsted and J. Kopeček: Pharm. Res., Vol. 9 (1992) p.1540.

Google Scholar

[36] A. T. Metters, K. S. Anseth and C. N. Bowman: Biomed. Sci. Instrum., Vol. 35 (1999) p.33.

Google Scholar

[37] Y. Jiao et al.: J. Appl. Polym. Sci., Vol. 101 (2006) p.1515.

Google Scholar

[38] S. Atzet et al.: Biomacromolecules, Vol. 9 (2008) p.3370.

Google Scholar

[39] M. J. Bruining et al.: J. Biomed. Mater. Res., Vol. 47 (1999) p.189.

Google Scholar

[40] M. J. Bruining et al.: Biomaterials, Vol. 21 (2000) p.595.

Google Scholar

[41] V. Bulmus, Y. Chan, Q. Nguyen and H. L. Tran: Macromol. Biosci., Vol. 7 (2007) p.446.

Google Scholar

[42] M. S. Taylor, A. U. Daniels, K. P. Andriano and J. Heller: J. Appl. Biomater., Vol. 5 (1994) p.151.

Google Scholar

[43] T. V. Chirila et al.: J. Cataract Refract. Surg., Vol. 17 (1991) p.154.

Google Scholar

[44] D. Horák, M. Červinka and V. Půža: Biomaterials, Vol. 18 (1997) p.1355.

Google Scholar

[45] R. V. Robinson, F. M. Sullivan, J. F. Borzelleca and S. L. Schwartz: PVP: A Critical Review of the Kinetics and Toxicology of Polyvinylpyrrolidone (Povidone), Lewis Publishers, Chelsea, MI (1990).

DOI: 10.1201/9780203741672

Google Scholar

[46] C. M. Porth, in: Pathophysiology: Concepts of Altered Health States, 8th Edn, edited by C. M. Porth and G. Matfin, Wolters Kluwer/Lippincott Williams Wilkins, Philadelphia (2009) p.740.

Google Scholar

[47] H. A. Ravin, A. M. Seligman and J. Fine: New Eng. J. Med., Vol. 247 (1952) p.921.

Google Scholar

[48] B. Hulme and J. Hardwicke: Proc. Roy. Soc. Med., Vol. 59 (1966) p.509.

Google Scholar

[49] J. D. Blainey, in: Enzymes in Urine and Kidney (Current Problems in Clinical Biochemistry: 2), edited by U. C. Dubach, Hans Huber Publishers, Bern (1968) p.85.

Google Scholar

[50] B. Hulme: Contrib. Nephrol., Vol. 1 (1975) p.3.

Google Scholar

[51] K. Gärtner, G. Vogel and M. Ulbrich: Pflügers Archiv, Vol. 298 (1968) p.305.

Google Scholar

[52] J. M. Healy et al.: Pharm. Res., Vol. 21 (2004) p.2234.

Google Scholar

[53] H. Petersen et al.: Bioconjugate Chem., Vol. 13 (2002) p.812.

Google Scholar

[54] X. Jiang, M. C. Lok and W. W. Hennink: Bioconjugate Chem., Vol. 18 (2007) p. (2077).

Google Scholar

[55] R. Plummer, Y. -K. Goh, A. K. Whittaker and M. J. Monteiro: Macromolecules, Vol. 38 (2005) p.5352.

Google Scholar

[56] K. L. Beers, S. Boo, S. G. Gaynor and K. Matyjaszewski: Macromolecules, Vol. 32 (1999) p.5772.

Google Scholar

[57] J. V. M. Weaver et al.: Macromolecules, Vol. 37 (2004) p.2395.

Google Scholar

[58] P. N. Patel, A. S. Gobin, J. L. West and C. W. Patrick, Jr.: Tissue Eng., Vol. 11 (2005) p.1498.

Google Scholar

[59] J. Zhu et al.: Macromolecules, Vol. 39 (2006) p.1305.

Google Scholar

[60] S. Oae, T. Yagihara and T. Okabe: Tetrahedron, Vol. 28 (1972) p.3203.

Google Scholar

[61] C. Barner-Kowollik, P. Vana, J. F. Quinn and T. P. Davis: J. Polym. Sci. A: Polym. Chem., Vol. 40 (2002) p.1058.

Google Scholar

[62] S. Braun, H. -O. Kalinowski and S. Berger: 150 and More Basic NMR Experiments: a Practical Course, Wiley-VCH, Weinheim (1998).

DOI: 10.1002/(sici)1097-458x(199909)37:9<690::aid-mrc493>3.0.co;2-q

Google Scholar

[63] T. D. W. Claridge: High-Resolution NMR Techniques in Organic Chemistry, Pergamon, New York (1999).

Google Scholar

[64] D. O. Cicero, G. Barbato and R. Bazzo: J. Magn. Reson., Vol. 148 (2001) p.209.

Google Scholar

[65] T. D. W. Claridge and I. Perez-Victoria: Org. Biomol. Chem., Vol. 1 (2003) p.3632.

Google Scholar

[66] A. Jerschow and N. Müller: J. Magn. Reson., Vol. 125 (1997) p.372.

Google Scholar

[67] J. Evans: Biomolecular NMR Spectroscopy, Oxford University Press, Oxford (1995).

Google Scholar

[68] B. Liu, A. Kazlauciunas, J. T. Guthrie and S. Perrier, Macromolecules, Vol. 38 (2005) p.2131.

Google Scholar

[69] M. Kiremitçi, H. Çukurova and S. Özkar: Polym. Int., Vol. 30 (1993) p.357.

Google Scholar

[70] A. R. Lim, G. T. Schueneman and B. M. Novak: Solid State Commun., Vol. 109 (1999) p.465.

Google Scholar

[71] A. Asano, M. Eguchi and T. Kurotu: J. Therm. Anal. Calorim., Vol. 56 (1999) p.1059.

Google Scholar

[72] E. Pretsch, P. Bühlmann and C. Affolter: Structure Determination of Organic Compounds: Tables of Spectral Data, 3rd Edn, Springer, Berlin (2000).

DOI: 10.1007/978-3-662-04201-4_3

Google Scholar

[73] M. F. Refojo: J. Polym. Sci. A-1, Vol. 5 (1967) p.3103.

Google Scholar

[74] K. Dušek, M. Bohdanecky and V. Vosicky: Coll. Czechoslov. Chem. Commun., Vol. 42 (1977) p.1599.

Google Scholar

[75] N. S. Khelfallah, G. Decher and P. J. Mésini: Macromol. Rapid Commun. Vol. 27 (2006) p.1004.

DOI: 10.1002/marc.200600210

Google Scholar