Biodegradable hydrogels composed of oxime crosslinked poly(ethylene glycol), hyaluronic acid and collagen: a tunable platform for soft tissue engineering

Abstract

In situ crosslinking hydrogels are attractive for application as injectable hydrogel-based tissue scaffolds that adapt to fill patient-specific cavities. Oxime click chemistry was used to crosslink hydrogels that were biodegradable, soft and supportive of cell adhesion. Linear poly(ethylene glycol)s (PEGs, Mn 2 or 4 kDa) terminated at both ends with aminooxy moieties and hyaluronic acid (HA, Mn 2 MDa) derivatives displaying aldehydes were non-toxic towards primary Schwann cells. The PEG and HA derivatives form oxime crosslinked hydrogels with mechanical and swelling properties that were tunable based on the composition of the hydrogels to values analogous to soft tissues such as those found in the central or peripheral nervous system. Gels incorporating collagen-1 supported the adhesion of human mesenchymal stem cells. Such chemistry has the potential to generate clinically relevant injectable hydrogels for minimally invasive personalized medical procedures in the central or peripheral nervous systems.

Keywords:

• biodegradable
• biomaterials
• biomimetic mechanical properties
• central nervous system
• peripheral nervous system
• in vitro cell culture
• injectable hydrogels
• tissue engineering

Acknowledgements

We thank the University of Texas at Austin for financial support of Phillip Lin in the form of an Undergraduate Research Fellowship. At the Department of Chemistry at the University of Texas at Austin, we thank Prof. Michael J. Krische for access to an IR spectrometer. At the University of Florida, we thank Maria K. Villancio-Wolter for assistance with cell counting. We thank the University of Florida for financial support in the form of start-up resources.

Additional information

Funding

Funding. This work was supported by the National Science Foundation under [grant number CBET 1159774]; and the National Institute of Health under [grant number 5R21NS074162-02].