Skip to main content
SpringerLink
Log in

In Vivo Characterization of Poly(ethylene glycol) Hydrogels with Thio-β Esters

  • Bioengineering and Enabling Technologies
  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Resorbable hydrogels have numerous potential applications in tissue engineering and drug delivery due to their highly tunable properties and soft tissue-like mechanical properties. The incorporation of esters into the backbone of poly(ethylene glycol) hydrogels has been used to develop libraries of hydrogels with tunable degradation rates. However, these synthetic strategies used to increase degradation rate often result in undesired changes in the hydrogel physical properties such as matrix modulus or swelling. In an effort to decouple degradation rate from other hydrogel properties, we inserted thio-β esters into the poly(ethylene glycol)-diacrylate backbone to introduce labile bonds without changing macromer molecular weight. This allowed the number of hydrolytically labile thio-β esters to be controlled through changing the ratios of this modified macromer to the original macromer without affecting network properties. The retention of hydrogel properties at different macromer ratios was confirmed by measuring gel fraction, swelling ratio, and compressive modulus. The tunable degradation profiles were characterized both in vitro and in vivo. Following confirmation of cytocompatibility after exposure to the hydrogel degradation products, the in vivo host response was evaluated in comparison to medical grade silicone. Collectively, this work demonstrates the utility and tunability of these hydrolytically degradable hydrogels for a wide variety of tissue engineering applications.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Anderson, D. G., C. A. Tweedie, N. Hossain, S. M. Navarro, D. M. Brey, K. J. Van Vliet, R. Langer, and J. A. Burdick. A combinatorial library of photocrosslinkable and degradable materials. Adv. Mater. 18:2614–2618, 2006.

    CAS  Google Scholar 

  2. Anseth, K. S., C. N. Bowman, and L. Brannon-Peppas. Mechanical properties of hydrogels and their experimental determination. Biomaterials 17:1647–1657, 1996.

    CAS  PubMed  Google Scholar 

  3. Anseth, K. S., A. T. Metters, S. J. Bryant, P. J. Martens, J. H. Elisseeff, and C. N. Bowman. In situ forming degradable networks and their application in tissue engineering and drug delivery. J. Control. Release 78:199–209, 2002.

    CAS  PubMed  Google Scholar 

  4. Basu, A., K. R. Kunduru, S. Doppalapudi, A. J. Domb, and W. Khan. Poly(lactic acid) based hydrogels. Adv. Drug Deliv. Rev. 107:192–205, 2016.

    CAS  PubMed  Google Scholar 

  5. Bencherif, S. A., J. A. Sheehan, J. O. Hollinger, L. M. Walker, K. Matyjaszewski, and N. R. Washburn. Influence of cross-linker chemistry on release kinetics of PEG-co-PGA hydrogels. J. Biomed. Mater. Res. A 90:142–153, 2009.

    PubMed  Google Scholar 

  6. Benoit, D. S., A. R. Durney, and K. S. Anseth. Manipulations in hydrogel degradation behavior enhance osteoblast function and mineralized tissue formation. Tissue Eng. 12:1663–1673, 2006.

    CAS  PubMed  Google Scholar 

  7. Biswal, D., P. P. Wattamwar, T. D. Dziubla, and J. Z. Hilt. A single-step polymerization method for poly (β-amino ester) biodegradable hydrogels. Polymer 52:5985–5992, 2011.

    CAS  Google Scholar 

  8. Brandl, F. P., A. K. Seitz, J. K. Teßmar, T. Blunk, and A. M. Göpferich. Enzymatically degradable poly (ethylene glycol) based hydrogels for adipose tissue engineering. Biomaterials 31:3957–3966, 2010.

    CAS  PubMed  Google Scholar 

  9. Brey, D. M., I. Erickson, and J. A. Burdick. Influence of macromer molecular weight and chemistry on poly (β-amino ester) network properties and initial cell interactions. J. Biomed. Mater. Res. A 85:731–741, 2008.

    PubMed  PubMed Central  Google Scholar 

  10. Browning, M. B., S. Cereceres, P. Luong, and E. Cosgriff-Hernandez. Determination of the in vivo degradation mechanism of PEGDA hydrogels. J. Biomed. Mater. Res. A 102:4244–4251, 2014.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Browning, M. B., and E. Cosgriff-Hernandez. Development of a biostable replacement for PEGDA hydrogels. Biomacromolecules 13:779–786, 2012.

    CAS  PubMed  Google Scholar 

  12. Browning, M. B., B. Russell, J. Rivera, M. Hook, and E. M. Cosgriff-Hernandez. Bioactive hydrogels with enhanced initial and sustained cell interactions. Biomacromolecules 14:2225–2233, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Browning, M. B., T. Wilems, M. Hahn, and E. Cosgriff-Hernandez. Compositional control of poly (ethylene glycol) hydrogel modulus independent of mesh size. J. Biomed. Mater. Res. A 98:268–273, 2011.

    CAS  PubMed  Google Scholar 

  14. Censi, R., W. Schuurman, J. Malda, G. Di Dato, P. E. Burgisser, W. J. Dhert, C. F. Van Nostrum, P. Di Martino, T. Vermonden, and W. E. Hennink. A printable photopolymerizable thermosensitive p (HPMAm-lactate)-PEG hydrogel for tissue engineering. Adv. Funct. Mater. 21:1833–1842, 2011.

    CAS  Google Scholar 

  15. Cereceres, S., T. Touchet, M. B. Browning, C. Smith, J. Rivera, M. Höök, C. Whitfield-Cargile, B. Russell, and E. Cosgriff-Hernandez. Chronic wound dressings based on collagen-mimetic proteins. Adv. Wound Care 4:444–456, 2015.

    Google Scholar 

  16. Chen, J., H. Park, and K. Park. Synthesis of superporous hydrogels: hydrogels with fast swelling and superabsorbent properties. J. Biomed. Mater. Res. 44:53–62, 1999.

    CAS  PubMed  Google Scholar 

  17. Chiu, Y.-C., M.-H. Cheng, H. Engel, S.-W. Kao, J. C. Larson, S. Gupta, and E. M. Brey. The role of pore size on vascularization and tissue remodeling in PEG hydrogels. Biomaterials 32:6045–6051, 2011.

    CAS  PubMed  Google Scholar 

  18. Cosgriff-Hernandez, E., M. Hahn, B. Russell, T. Wilems, D. Munoz-Pinto, M. Browning, J. Rivera, and M. Höök. Bioactive hydrogels based on designer collagens. Acta Biomater. 6:3969–3977, 2010.

    CAS  PubMed  Google Scholar 

  19. DeFail, A. J., C. R. Chu, N. Izzo, and K. G. Marra. Controlled release of bioactive TGF-β1 from microspheres embedded within biodegradable hydrogels. Biomaterials 27:1579–1585, 2006.

    CAS  PubMed  Google Scholar 

  20. Franssen, O., O. P. Vos, and W. E. Hennink. Delayed release of a model protein from enzymatically-degrading dextran hydrogels. J. Control. Release 44:237–245, 1997.

    CAS  Google Scholar 

  21. Hahn, M. S., L. J. Taite, J. J. Moon, M. C. Rowland, K. A. Ruffino, and J. L. West. Photolithographic patterning of polyethylene glycol hydrogels. Biomaterials 27:2519–2524, 2006.

    CAS  PubMed  Google Scholar 

  22. Hao, Y., and C. C. Lin. Degradable thiol-acrylate hydrogels as tunable matrices for three-dimensional hepatic culture. J. Biomed. Mater. Res. A 102:3813–3827, 2014.

    PubMed  Google Scholar 

  23. Hoffman, A. S. Hydrogels for biomedical applications. Adv. Drug Deliv. Rev. 64:18–23, 2012.

    Google Scholar 

  24. Hubbell, J. A. Bioactive biomaterials. Curr. Opin. Biotechnol. 10:123–129, 1999.

    CAS  PubMed  Google Scholar 

  25. Hudalla, G. A., T. S. Eng, and W. L. Murphy. An approach to modulate degradation and mesenchymal stem cell behavior in poly (ethylene glycol) networks. Biomacromolecules 9:842–849, 2008.

    CAS  PubMed  Google Scholar 

  26. Jongpaiboonkit, L., W. J. King, G. E. Lyons, A. L. Paguirigan, J. W. Warrick, D. J. Beebe, and W. L. Murphy. An adaptable hydrogel array format for 3-dimensional cell culture and analysis. Biomaterials 29:3346–3356, 2008.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Jongpaiboonkit, L., W. J. King, and W. L. Murphy. Screening for 3D environments that support human mesenchymal stem cell viability using hydrogel arrays. Tissue Eng. A 15:343–353, 2008.

    Google Scholar 

  28. Kharkar, P. M., K. L. Kiick, and A. M. Kloxin. Designing degradable hydrogels for orthogonal control of cell microenvironments. Chem. Soc. Rev. 42:7335–7372, 2013.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. King, W. J., L. Jongpaiboonkit, and W. L. Murphy. Influence of FGF2 and PEG hydrogel matrix properties on hMSC viability and spreading. J. Biomed. Mater. Res. A 93:1110–1123, 2010.

    PubMed  PubMed Central  Google Scholar 

  30. Lee, K. Y., and D. J. Mooney. Hydrogels for tissue engineering. Chem. Rev. 101:1869–1880, 2001.

    CAS  PubMed  Google Scholar 

  31. Li, Q., J. Wang, S. Shahani, D. D. Sun, B. Sharma, J. H. Elisseeff, and K. W. Leong. Biodegradable and photocrosslinkable polyphosphoester hydrogel. Biomaterials 27:1027–1034, 2006.

    CAS  PubMed  Google Scholar 

  32. Lutolf, M., J. Lauer-Fields, H. Schmoekel, A. T. Metters, F. Weber, G. Fields, and J. A. Hubbell. Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc. Natl. Acad. Sci. U.S.A. 100:5413–5418, 2003.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Lynn, A. D., T. R. Kyriakides, and S. J. Bryant. Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels. J. Biomed. Mater. Res. A 93:941–953, 2010.

    PubMed  Google Scholar 

  34. Mann, B. K., A. S. Gobin, A. T. Tsai, R. H. Schmedlen, and J. L. West. Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. Biomaterials 22:3045–3051, 2001.

    CAS  PubMed  Google Scholar 

  35. Mawad, D., L. A. Poole-Warren, P. Martens, L. H. Koole, T. L. Slots, and C. S. van Hooy-Corstjens. Synthesis and characterization of radiopaque iodine-containing degradable PVA hydrogels. Biomacromolecules 9:263–268, 2008.

    CAS  PubMed  Google Scholar 

  36. Metters, A. T., K. S. Anseth, and C. N. Bowman. Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel. Polymer 41:3993–4004, 2000.

    CAS  Google Scholar 

  37. Metters, A. T., and J. Hubbell. Network formation and degradation behavior of hydrogels formed by Michael-type addition reactions. Biomacromolecules 6:290–301, 2005.

    CAS  PubMed  Google Scholar 

  38. Nicodemus, G. D., and S. J. Bryant. Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng. B 14:149–165, 2008.

    CAS  Google Scholar 

  39. Parlato, M., S. Reichert, N. Barney, and W. L. Murphy. Poly(ethylene glycol) hydrogels with adaptable mechanical and degradation properties for use in biomedical applications. Macromol. Biosci. 14:687–698, 2014.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Peppas, N. A., P. Bures, W. Leobandung, and H. Ichikawa. Hydrogels in pharmaceutical formulations. Eur. J. Pharm. Biopharm. 50:27–46, 2000.

    CAS  PubMed  Google Scholar 

  41. Peppas, N. A., J. Z. Hilt, A. Khademhosseini, and R. Langer. Hydrogels in biology and medicine: from molecular principles to bionanotechnology. Adv. Mater. 18:1345–1360, 2006.

    CAS  Google Scholar 

  42. Qiu, Y., J. J. Lim, L. Scott, R. C. Adams, H. T. Bui, and J. S. Temenoff. PEG-based hydrogels with tunable degradation characteristics to control delivery of marrow stromal cells for tendon overuse injuries. Acta Biomater. 7:959–966, 2011.

    CAS  PubMed  Google Scholar 

  43. Safranski, D. L., D. Weiss, J. B. Clark, B. S. Caspersen, W. R. Taylor, and K. Gall. Effect of poly (ethylene glycol) diacrylate concentration on network properties and in vivo response of poly (β-amino ester) networks. J. Biomed. Mater. Res. A 96:320–329, 2011.

    PubMed  Google Scholar 

  44. Sebra, R. P., K. S. Masters, C. N. Bowman, and K. S. Anseth. Surface grafted antibodies: controlled architecture permits enhanced antigen detection. Langmuir 21:10907–10911, 2005.

    CAS  PubMed  Google Scholar 

  45. Slaughter, B. V., S. S. Khurshid, O. Z. Fisher, A. Khademhosseini, and N. A. Peppas. Hydrogels in regenerative medicine. Adv. Mater. 21:3307–3329, 2009.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Suggs, L. J., R. S. Krishnan, C. A. Garcia, S. J. Peter, J. M. Anderson, and A. G. Mikos. In vitro and in vivo degradation of poly (propylene fumarate-co-ethylene glycol) hydrogels. J. Biomed. Mater. Res. 42:312–320, 1998.

    CAS  PubMed  Google Scholar 

  47. Van de Wetering, P., A. T. Metters, R. G. Schoenmakers, and J. A. Hubbell. Poly(ethylene glycol) hydrogels formed by conjugate addition with controllable swelling, degradation, and release of pharmaceutically active proteins. J. Control. Release 102:619–627, 2005.

    PubMed  Google Scholar 

  48. West, J. L., and J. A. Hubbell. Polymeric biomaterials with degradation sites for proteases involved in cell migration. Macromolecules 32:241–244, 1999.

    CAS  Google Scholar 

  49. Zaquen, N., B. Wenn, K. Ranieri, J. Vandenbergh, and T. Junkers. Facile design of degradable poly (β-thioester)s with tunable structure and functionality. J. Polym. Sci. A 52:178–187, 2014.

    CAS  Google Scholar 

  50. Zhu, J. Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31:4639–4656, 2010.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Zustiak, S. P., and J. B. Leach. Hydrolytically degradable poly (ethylene glycol) hydrogel scaffolds with tunable degradation and mechanical properties. Biomacromolecules 11:1348–1357, 2010.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843, USA

    Stacy Cereceres, Michael Whitely & Natalia Fabela

  2. Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton, BME 3.503D, 1 University Station, C0800, Austin, TX, 78712, USA

    Ziyang Lan, Thomas Wilems & Elizabeth Cosgriff-Hernandez

  3. Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA

    Laura Bryan

  4. Department of Large Animal Clinical Sciences, Texas A&M University, College Station, TX, 77843, USA

    Canaan Whitfield-Cargile

Authors
  1. Stacy Cereceres
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ziyang Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laura Bryan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael Whitely
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Wilems
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natalia Fabela
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Canaan Whitfield-Cargile
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Elizabeth Cosgriff-Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elizabeth Cosgriff-Hernandez.

Additional information

Associate Editor Emmanuel Opara oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 617 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cereceres, S., Lan, Z., Bryan, L. et al. In Vivo Characterization of Poly(ethylene glycol) Hydrogels with Thio-β Esters. Ann Biomed Eng 48, 953–967 (2020). https://doi.org/10.1007/s10439-019-02271-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-019-02271-8

Keywords

Search

Navigation