Calcium-alginate hydrogel-encapsulated fibroblasts provide sustained release of vascular endothelial growth factor.
Vascularization of engineered or damaged tissues is essential to maintain cell viability and proper tissue function. Revascularization of the left ventricle (LV) of the heart after myocardial infarction is particularly important, since hypoxia can give rise to chronic heart failure due to inappropriate remodeling of the LV after death of cardiomyocytes (CMs). Fibroblasts can express vascular endothelial growth factor (VEGF), which plays a major role in angiogenesis and also acts as a chemoattractant and survival factor for CMs 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. Semiquantitative reverse transcription-polymerase chain reaction and immunohistochemistry demonstrated that over 21 days of encapsulation, fibroblasts continued to express VEGF, while enzyme-linked immunosorbent assay showed that 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 after scaffold degradation. This model in vitro study therefore demonstrates that fibroblasts encapsulated in Ca-alginate provide sustained release of VEGF.
International Centre for Life, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
Nicola C
NC
Hunt
Richard M
RM
Shelton
Deborah J
DJ
Henderson
Liam M
LM
Grover
D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D018914:Cells, Immobilized / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D008863:Microspheres; D041681:NIH 3T3 Cells; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013194:Staining and Labeling; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000464:Alginates; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D042461:Vascular Endothelial Growth Factor A; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid