Calcium-alginate hydrogel encapsulated fibroblasts provide sustained release of vascular endothelial growth factor

Vascularisation of engineered or damaged tissues is essential to maintain cell viability and proper tissue function. Re-vascularisation of the left ventricle (LV) of heart after myocardial infarction is particularly important, since hypoxia can give rise to chronic heart failure due to inappropriate remodelling of the LV following death of cardiomyocytes. Fibroblasts can express vascular endothelial growth factor (VEGF), which plays a major role in angiogenesis and also acts as a chemo-attractant and survival factor for cardiomyocytes and cardiac progenitors. In this in vitro model study mouse NIH 3T3 fibroblasts encapsulated in 2% w/v Ca-alginate were shown to remain viable for 150 days. Semi-quantitative reverse transcription PCR (sqRT-PCR) and immunohistochemistry (IHC) demonstrated that over 21 days encapsulation fibroblasts continued to express VEGF whilst enzyme-linked immunosorbent assay (ELISA) showed there was sustained release of VEGF from the Ca-alginate during this period. The scaffold degraded gradually over the 21 days, without reduction in volume.. Cells released from the Ca-alginate at 7 and 21 days as a result of scaffold degradation were shown to retain viability, to adhere to fibronectin in a normal manner, and continue to express VEGF demonstrating their potential to further contribute to maintenance of cardiac function following scaffold degradation. This model in vitro study therefore demonstrates that fibroblasts encapsulated in Ca-alginate provide sustained release of VEGF.