Application of UVA-riboflavin crosslinking to enhance the mechanical properties of extracellular matrix derived hydrogels

Hydrogels derived from extracellular matrix (ECM) have become increasing popular in recent years, particularly for use in tissue engineering. One limitation with ECM hydrogels is that they tend to have poor mechanical properties compared to native tissues they are trying to replicate. To address this problem, a UVA (ultraviolet-A) riboflavin crosslinking technique was applied to ECM hydrogels to determine if it could be used to improve their elastic modulus. Hydrogels fabricated from corneal, cardiac and liver ECM were used in this study. The mechanical properties of the hydrogels were characterized using a spherical indentation technique. The microstructure of the hydrogels and the cytotoxic effect of crosslinking on cell seeded hydrogels were also evaluated. The combination of WA light and riboflavin solution led to a significant increase in elastic modulus from 6.8 kPa to 24.7 kPa, 1.4 kPa to 6.9 kPa and 0.9 kPa to 1.6 kPa for comeal, cardiac and liver ECM hydrogels respectively. The extent of this increase was dependent on a number of factors including the WA exposure time and the initial hydrogel concentration. There were also a high percentage of viable cells within the cell seeded hydrogels with 94% of cells remaining viable after 90 min exposure to WA light. These results suggest that UVA-riboflavin crosslinking is an effective approach for improving the mechanical properties of ECM hydrogels without resulting in a significant reduction of cell viability. (C) 2015 Elsevier Ltd. All rights reserved.