Skip to main content
Log in

Rheological characterization of biocompatible associative polymer hydrogels with crystalline and amorphous endblocks

  • Article
  • Published:
Journal of Materials Research Aims and scope Submit manuscript

Abstract

Control over mechanical properties of hydrogels is of primary importance for the use of these materials in drug delivery and tissue engineering applications. We demonstrate here that crystallinity and block length of poly(lactide) (PLA) can be used to tune the elastic modulus of associative network gels of poly(lactide)–poly(ethylene oxide)–poly(lactide) over several orders of magnitude. Polymers made with crystalline L lactic acid blocks formed very stiff hydrogels at 25 wt% concentration with an elastic modulus that was almost an order of magnitude higher than hydrogels of polymers with a similar molecular weight but containing amorphous D/L-lactic acid blocks. The relaxation behavior and crosslink density of gels are also significantly influenced by crystallinity of PLA and are again a function of PLA block length. Using these variables we can design new tailor-made materials for biomedical applications with precise control over their structure and mechanical properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. A.J. Engler, M.A. Griffin, S. Sen, C.G. Bonnetnann, H.L. Sweeney, D.E. Discher: Myotubes differentiate optimally on substrates with tissue-like stiffness: Pathological implications for soft or stiff microenvironments. J. Cell Biol. 166, 877 (2004).

    CAS  Google Scholar 

  2. D.E. Discher, P. Janmey, Y.L. Wang: Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139 (2005).

    CAS  Google Scholar 

  3. A.J. Engler, H.L. Sweeney, D.E. Discher: Substrate elasticity alters human mesenchymal stem cell differentiation. Biophys. J. 88, 500A (2005).

    Google Scholar 

  4. G. Bao, S. Suresh: Cell and molecular mechanics of biological materials. Nat. Mater. 2, 715 (2003).

    CAS  Google Scholar 

  5. K.Y. Lee, D.J. Mooney: Hydrogels for tissue engineering. Chem. Rev. 101, 1869 (2001).

    CAS  Google Scholar 

  6. A.S. Hoffman: Hydrogels for biomedical applications. Adv. Drug Delivery Rev. 54(1), 3 (2002).

    CAS  Google Scholar 

  7. T. Kissel, Y.X. Li, F. Unger: ABA-triblock copolymers from biodegradable polyester A-blocks and hydrophilic poly(ethylene oxide) B-blocks as a candidate for in situ forming hydrogel delivery systems for proteins. Adv. Drug Delivery Rev. 54(1), 99 (2002).

    CAS  Google Scholar 

  8. R. Langer, N.A. Peppas: Advances in biomaterials, drug delivery, and bionanotechnology. AIChE J. 49, 2990 (2003).

    CAS  Google Scholar 

  9. M.J. Yaszemski: Tissue Engineering and Novel Delivery System (Marcel Dekker, New York, 2004), pp. vii, 645.

    Google Scholar 

  10. G.N. Tew, N. Sanabria-DeLong, S.K. Agrawal, S.R. Bhatia: New properties from PLA-PEO-PLA hydrogels. Soft Matter 1, 253 (2005).

    CAS  Google Scholar 

  11. J.J. Bi, J.C. Downs, J.T. Jacob: Tethered protein/peptide-surface-modified hydrogels. J. Biomater. Sci. Polym. Ed. 15, 905 (2004).

    CAS  Google Scholar 

  12. S.E. Noorjahan, T.P. Sastry: An in vivo study of hydrogels based on physiologically clotted fibrin-gelatin composites as wound-dressing materials. J. Biomed. Mater. Res. B Appl. Biomater. 71B, 305 (2004).

    CAS  Google Scholar 

  13. K.A. Aamer, H. Sardinha, S.R. Bhatia, G.N. Tew: Rheological studies of PLLA-PEO-PLLA triblock copolymer hydrogels. Biomaterials 25, 1087 (2004).

    CAS  Google Scholar 

  14. A.P. Nowak, V. Breedveld, L. Pakstis, B. Ozbas, D.J. Pine, D. Pochan, T.J. Deming: Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles. Nature 417, 424 (2002).

    CAS  Google Scholar 

  15. B.L. Seal, A. Panitch: Physical polymer matrices based on affinity interactions between peptides and polysaccharides. Biomacromolecules 4, 1572 (2003).

    CAS  Google Scholar 

  16. R.B. Vernon, M.D. Gooden, S.L. Lara, T.N. Wight: Native fibrillar collagen membranes of micron-scale and submicron thicknesses for cell support and perfusion. Biomaterials 26, 1109 (2005).

    CAS  Google Scholar 

  17. S.K. Choi, D. Kim: Drug-releasing behavior of MPEG/PLA block copolymer micelles and solid particles controlled by component block length. J. Appl. Polym. Sci. 83, 435 (2002).

    CAS  Google Scholar 

  18. B. Jeong, Y.H. Bae, D.S. Lee, S.W. Kim: Biodegradable block copolymers as injectable drug delivery systems. Nature 388, 860 (1997).

    CAS  Google Scholar 

  19. B. Jeong, M.R. Kibbey, J.C. Birnbaum, Y.Y. Won, A. Gutowska: Thermogelling biodegradable polymers with hydrophilic backbones: PEG-g-PLGA. Macromolecules 33, 8317 (2000).

    CAS  Google Scholar 

  20. H.R. Kricheldorf, J. Meierhaack: Polylactones.22. ABA triblock copolymers of L-lactide and poly(ethylene glycol). Macromol. Chem. Phys. 194, 715 (1993).

    CAS  Google Scholar 

  21. D. Kubies, F. Rypacek, J. Kovarova, F. Lednicky: Microdomain structure in polylactide-block-poly(ethylene oxide) copolymer films. Biomaterials 21, 529 (2000).

    CAS  Google Scholar 

  22. S.M. Li, I. Rashkov, J.L. Espartero, N. Manolova, M. Vert: Synthesis, characterization, and hydrolytic degradation of PLA/PEO/PLA triblock copolymers with long poly(L-lactic acid) blocks. Macromolecules 29, 57 (1996).

    CAS  Google Scholar 

  23. Y.X. Li, T. Kissel: Synthesis and properties of biodegradable ABA triblock copolymers consisting of poly(L-lactic acid) or poly(L-lactic-Co-glycolic acid) A-blocks attached to central poly(oxyethylene) B-Blocks. J. Controlled Release 27, 247 (1993).

    CAS  Google Scholar 

  24. Y.X. Li, C. Volland, T. Kissel: In-vitro degradation and bovine serum-albumin release of the Aba triblock copolymers consisting of poly(L(+)lactic acid), or poly(L(+)lactic acid-Co-glycolic acid) A-blocks attached to central polyoxyethylene B-blocks. J. Controlled Release 32, 121 (1994).

    Google Scholar 

  25. L. Liu, C.X. Li, X.H. Liu, B.L. He: Micellar formation in aqueous milieu from biodegradable triblock copolymer polylactide/poly(ethylene glycol)/polylactide. Polym. J. 31, 845 (1999).

    CAS  Google Scholar 

  26. I. Molina, S.M. Li, M.B. Martinez, M. Vert: Protein release from physically crosslinked hydrogels of the PLA/PEO/PLA triblock copolymer-type. Biomaterials 22, 363 (2001).

    CAS  Google Scholar 

  27. I. Rashkov, N. Manolova, S.M. Li, J.L. Espartero, M. Vert: Synthesis, characterization, and hydrolytic degradation of PLA/PEO/PLA triblock copolymers with short poly(L-lactic acid) chains. Macromolecules 29, 50 (1996).

    CAS  Google Scholar 

  28. N. Saito, T. Okada, H. Horiuchi, N. Murakami, J. Takahashi, M. Nawata, H. Ota, K. Nozaki, K. Takaoka: A biodegradable polymer as a cytokine delivery system for inducing bone formation. Nat. Biotechnol. 19, 332 (2001).

    CAS  Google Scholar 

  29. K. Yasugi, Y. Nagasaki, M. Kato, K. Kataoka: Preparation and characterization of polymer micelles from poly(ethylene glycol)-poly(D,L-lactide) block copolymers as potential drug carrier. J. Controlled Release 62(1-2), 89 (1999).

    CAS  Google Scholar 

  30. D.S. Lee, M.S. Shim, S.W. Kim, H. Lee, I. Park, T.Y. Chang: Novel thermoreversible gelation of biodegradable PLGA-block- PEO-block-PLGA triblock copolymers in aqueous solution. Macromol. Rapid Commun. 22, 587 (2001).

    CAS  Google Scholar 

  31. H.T. Lee, D.S. Lee: Thermoresponsive phase transitions of PLA-block-PEO-block-PLA triblock stereo-copolymers in aqueous solution. Macromol. Res. 10, 359 (2002).

    CAS  Google Scholar 

  32. M.S. Shim, H.T. Lee, W.S. Shim, I. Park, H. Lee, T. Chang, S.W. Kim, D.S. Lee: Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)- b-poly (D,L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water. J. Biomed. Mater. Res. 61, 188 (2002).

    CAS  Google Scholar 

  33. B. Jeong, Y.H. Bae, S.W. Kim: Thermoreversible gelation of PEG-PLGA-PEG triblock copolymer aqueous solutions. Macromolecules 32, 7064 (1999).

    CAS  Google Scholar 

  34. B. Jeong, S.W. Kim, Y.H. Bae: Thermosensitive sol-gel reversible hydrogels. Adv. Drug Delivery Rev. 54(1), 37 (2002).

    CAS  Google Scholar 

  35. S.K. Agrawal, K.S. Chin, N. Sanabria-DeLong, K.A. Aamer, H. Sardinha, G.N. Tew, S.C. Robert, and S.R. Bhatia: Rheology and biocompatibility of poly(lactide)-poly(ethylene oxide)-poly(lactide) hydrogels, in Mechanical Properties of Bioinspired and Biological Materials edited by C. Viney, K. Katti, F.J. Ulm, and C. Hellmich (Mater. Res. Soc. Symp. Proc. 844, Warrendale, PA, 2005), Y9.8, p. 327.

    Google Scholar 

  36. T. Annable, R. Buscall, R. Ettelaie, D. Whittlestone: The rheology of solutions of associating polymers–Comparison of experimental behavior with transient network theory. J. Rheol. 37, 695 (1993).

    CAS  Google Scholar 

  37. A.N. Semenov, J.F. Joanny, A.R. Khokhlov: Associating polymers–Equilibrium and linear viscoelasticity. Macromolecules 28, 1066 (1995).

    CAS  Google Scholar 

  38. Y. Serero, R. Aznar, G. Porte, J.F. Berret, D. Calvet, A. Collet, M. Viguier: Associating polymers: From “flowers” to transient networks. Phys. Rev. Lett. 81, 5584 (1998).

    CAS  Google Scholar 

  39. F. Tanaka, S.F. Edwards: Viscoelastic properties of physically cross-linked networks–Transient network theory. Macromolecules 25, 1516 (1992).

    CAS  Google Scholar 

  40. N. Sanabria-DeLong, S.K. Agrawal, S.R. Bhatia, G.N. Tew: Controlling hydrogel properties by crystallization of hydrophobic domains. Macromolecules 39, 1308 (2006).

    CAS  Google Scholar 

  41. G. Tae, J.A. Kornfield, J.A. Hubbell, D. Johannsmann, T.E. Hogen-Esch: Hydrogels with controlled, surface erosion characteristics from self-assembly of fluoroalkyl-ended poly(ethylene glycol). Macromolecules 34, 6409 (2001).

    CAS  Google Scholar 

  42. C.M. Hassan, N.A. Peppas: Structure and applications of poly(vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. Adv. Polym. Sci. 153, 37 (2000).

    CAS  Google Scholar 

  43. R. Ricciardi, G. D’Errico, F. Auriemma, G. Ducouret, A.M. Tedeschi, C. De Rosa, F. Laupretre, F. Lafuma: Short-time dynamics of solvent molecules and supramolecular organization of poly (vinyl alcohol) hydrogels obtained by freeze/thaw techniques. Macromolecules 38, 6629 (2005).

    CAS  Google Scholar 

  44. S. Misra, M. Nguyenmisra, W.L. Mattice: Bridging by reversibly adsorbed telechelic polymers—A transient network. Macromolecules 27, 5037 (1994).

    CAS  Google Scholar 

  45. Q.T. Pham, W.B. Russel, J.C. Thibeault, W. Lau: Micellar solutions of associative triblock copolymers: The relationship between structure and rheology. Macromolecules 32, 5139 (1999).

    CAS  Google Scholar 

  46. G.Y. Tae, J.A. Kornfield, J.A. Hubbell, J.S. Lal: Ordering transitions of fluoroalkyl-ended poly(ethylene glycol): Rheology and SANS. Macromolecules 35, 4448 (2002).

    CAS  Google Scholar 

  47. M.A. Winnik, A. Yekta: Associative polymers in aqueous solution. Curr. Opin. Colloid Interf. Sci. 2, 424 (1997).

    CAS  Google Scholar 

  48. B. Xu, L. Li, A. Yekta, Z. Masoumi, S. Kanagalingam, M.A. Winnik, K.W. Zhang, P.M. Macdonald: Synthesis, characterization, and rheological behavior of polyethylene glycols end-capped with fluorocarbon hydrophobes. Langmuir 13, 2447 (1997).

    CAS  Google Scholar 

  49. R. Stockwell, G. Meachim: The chondrocyte, in Adult Articular Cartilage, edited by M.A.R Freeman, (Pitman Medical, Tunbridge Wells, England, 1979).

  50. E.H. Frank, A.J. Grodzinsky: Cartilage electromechanics—II. A continuum model of cartilage electrokinetics and correlation with experiments. J. Biomech. Eng. 20, 629 (1987).

    CAS  Google Scholar 

  51. Q.L. Yu, J.B. Zhou, Y.C. Fung: Neutral axis location in bending and Young’s modulus of different layers of arterial wall. Am. J. Physiol. 265, H52 (1993).

    CAS  Google Scholar 

  52. F.J. Carter, T.G. Frank, P.J. Davies, D. McLean, A. Cuschieri: Measurements and modelling of the compliance of human and porcine organs. Med. Image Anal. 5, 231 (2001).

    CAS  Google Scholar 

  53. R.Q. Erkamp, P. Wiggins, A.R. Skovoroda, S.Y. Emelianov, M. O’Donnell: Measuring the elastic modulus of small tissue samples. Ultrason. Imaging 20, 17 (1998).

    CAS  Google Scholar 

  54. D.W. Hutmacher: Scaffold design and fabrication technologies for engineering tissues: State of the art and future perspectives. J. Biomater. Sci. Polym. Ed. 12, 107 (2001).

    CAS  Google Scholar 

  55. H.H. Winter, F. Chambon: Analysis of linear viscoelasticity of a cross-linking polymer at the gel point. J. Rheol. 30, 367 (1986).

    CAS  Google Scholar 

  56. Y.G. Lin, D.T. Mallin, J.C.W Chien, H.H. Winter: Dynamic mechanical measurement of crystallization-induced gelation in thermoplastic elastomeric poly(propylene). Macromolecules 24, 850 (1991).

    CAS  Google Scholar 

  57. H.W. Richtering, K.D. Gagnon, R.W. Lenz, R.C. Fuller, H.H. Winter: Physical gelation of a bacterial thermoplastic elastomer. Macromolecules 25, 2429 (1992).

    CAS  Google Scholar 

  58. F. Clement, A. Johner, J.F. Joanny, A.N. Semenov: Stress relaxation in telechelic gels. 1. Sticker extraction. Macromolecules 33, 6148 (2000).

    CAS  Google Scholar 

  59. M. Nguyenmisra, W.L. Mattice: Dynamics of end-associated triblock copolymer networks. Macromolecules 28, 6976 (1995).

    CAS  Google Scholar 

  60. D. Calvet, A. Collet, M. Viguier, J.F. Berret, Y. Serero: Perfluoroalkyl end-capped poly(ethylene oxide). Synthesis, characterization, and rheological behavior in aqueous solution. Macromolecules 36, 449 (2003).

    CAS  Google Scholar 

  61. T. Durrschmidt, H. Hoffmann: Organogels from ABA triblock copolymers. Colloid Polym. Sci. 279, 1005 (2001).

    CAS  Google Scholar 

  62. V. Castelletto, I.W. Hamley, X.F. Yuan, A. Kelarakis, C. Booth: Structure and rheology of aqueous micellar solutions and gels formed from an associative poly(oxybutylene)-poly(oxyethylene)-poly(oxybutylene) triblock copolymer. Soft Matter 1(2), 138 (2005).

    CAS  Google Scholar 

  63. K. Inomata, D. Nakanishi, A. Banno, E. Nakanishi, Y. Abe, R. Kurihara, K. Fujimoto, T. Nose: Association and physical gelation of ABA triblock copolymer in selective solvent. Polym. 44, 5303 (2003).

    CAS  Google Scholar 

  64. W.K. Ng, K.C. Tam, R.D. Jenkins: Lifetime and network relaxation time of a HEUR-C20 associative polymer system. J. Rheol. 44, 137 (2000).

    CAS  Google Scholar 

  65. N. Cathebras, A. Collet, M. Viguier, J.F. Berret: Synthesis and linear viscoelasticity of fluorinated hydrophobically modified ethoxylated urethanes (F-HEUR). Macromolecules 31, 1305 (1998).

    CAS  Google Scholar 

  66. M.S. Green, A.V. Tobolsky: A new approach to the theory of relaxing polymeric media. J. Chem. Phys. 14, 80 (1946).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gregory N. Tew.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Agrawal, S.K., Sanabria-DeLong, N., Tew, G.N. et al. Rheological characterization of biocompatible associative polymer hydrogels with crystalline and amorphous endblocks. Journal of Materials Research 21, 2118–2125 (2006). https://doi.org/10.1557/jmr.2006.0261

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1557/jmr.2006.0261

Navigation