Combining mechanical foaming and thermally induced phase separation to generate chitosan scaffolds for soft tissue engineering

Abstract

In this paper, a novel foaming methodology consisting of turbulent mixing and thermally induced phase separation (TIPS) was used to generate scaffolds for tissue engineering. Air bubbles were mechanically introduced into a chitosan solution which forms the continuous polymer/liquid phase in the foam created. The air bubbles entrained in the foam act as a template for the macroporous architecture of the final scaffolds. Wet foams were crosslinked via glutaraldehyde and frozen at −20 °C to induce TIPS in order to limit film drainage, bubble coalescence and Ostwald ripening. The effects of production parameters, including mixing speed, surfactant concentration and chitosan concentration, on foaming are explored. Using this method, hydrogel scaffolds were successfully produced with up to 80% porosity, average pore sizes of 120 μm and readily tuneable compressive modulus in the range of 2.6 to 25 kPa relevant to soft tissue engineering applications. These scaffolds supported 3T3 fibroblast cell proliferation and penetration and therefore show significant potential for application in soft tissue engineering.

Keywords:

• Foaming
• TIPS
• tissue engineering
• scaffolds
• chitosan
• PVA

Acknowledgements

The authors thank Benjamin Hibbs from the Advanced Fluorescence Imaging facility at the University of Melbourne for help with confocal imaging. We would also like to thank the Particulate Fluids Processing Centre (PFPC) for access to infrastructure and equipment. Dhee Biswas gratefully acknowledges the Australian Government for an Australian Postgraduate Award. P.A.T was recipient of the University of Melbourne’s McKenzie fellowship and the Seed Funding from the Melbourne Materials Institute and The Bio21 Institute of Molecular Science and Biotechnology (Bio21) and now is a Vice Chancellor’s Research Fellow at Queensland University of Technology.