Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel

  • Yixiao Dong
  • Waqar Hassan
  • Yu Zheng
  • Aram Omer Saeed
  • Hongliang Cao
  • Hongyun Tai
  • Abhay Pandit
  • Wenxin WangEmail author


Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an ‘one pot and one step’ in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, Mn = 258 g mol−1), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M= 475 g mol−1) and (2-methoxyethoxy) ethyl methacrylate (MEO2MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models.


Hyaluronic Acid Atom Transfer Radical Polymerization Lower Critical Solution Temperature Interpenetrate Polymer Network Copolymer Solution 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Science Foundation Ireland (SFI), SFI Principal Investigator programme, Heath Research Board (HRB) of Ireland, DEBRA Ireland and DEBRA Austria, National University of Ireland, Galway are gratefully acknowledged for funding. YD thanks Mohammad Abu-Rub and Estelle Collin in NFB for the help on hydrogel characterization and 3D cell culture work.

Supplementary material

10856_2011_4496_MOESM1_ESM.docx (77 kb)
Supplementary material 1 (DOCX 76 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Yixiao Dong
    • 1
  • Waqar Hassan
    • 1
  • Yu Zheng
    • 1
  • Aram Omer Saeed
    • 1
  • Hongliang Cao
    • 1
  • Hongyun Tai
    • 2
  • Abhay Pandit
    • 1
  • Wenxin Wang
    • 1
    Email author
  1. 1.Network of Excellence for Functional BiomaterialsNational University of IrelandGalwayIreland
  2. 2.School of ChemistryBangor UniversityBangorUK

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