In SituCrosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells.
Clinical trials utilizing mesenchymal stem cells (MSCs) for severe vascular diseases have highlighted the need to effectively engraft cells and promote pro-angiogenic activity. A functional material accomplishing these two goals is an ideal solution as spatiotemporal and batch-to-batch variability in classical therapeutic delivery can be minimized, and tissue regeneration would begin rapidly at the implantation site. Gelatin may serve as a promising biomaterial due to its excellent biocompatibility, biodegradability, and non-immuno/antigenicity. However, the dissolution of gelatin at body temperature and quick enzymatic degradationin vivo have limited its use thus far. To overcome these challenges, an injectable,in situcrosslinkable gelatin was developed by conjugating enzymatically-crosslinkable hydroxyphenyl propionic acid (GHPA). When MSCs are cultured in 3Din vitroor injectedin vivoin GHPA, spontaneous endothelial differentiation occurs, as evidenced by marked increases in endothlelial cell marker expressions (Flk1, Tie2, ANGPT1, vWF) in addition to forming an extensive perfusable vascular network after 2-week subcutaneous implantation. Additionally, favorable host macrophage response is achieved with GHPA as shown by decreased iNOS and increased MRC1 expression. These results indicate GHPA as a promising soluble factor-free cell delivery template which induces endothelial differentiation of MSCs with robust neovasculature formation and favorable host response.
Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235 USA; Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 37235 USA.
Sue Hyun
SH
Lee
Dept. of Molecular Science & Technology, Ajou University, Suwon 443-749 South Korea.
Yunki
Y
Lee
Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235 USA; Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 37235 USA.
Young Wook
YW
Chun
Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235 USA; Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 37235 USA.
Spencer W
SW
Crowder
Dept. of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37235 USA.
Pampee P
PP
Young
Dept. of Molecular Science & Technology, Ajou University, Suwon 443-749 South Korea.
Ki Dong
KD
Park
Dept. of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235 USA; Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, 37235 USA.
Hak-Joon
HJ
Sung
gelatin; in situ crosslinking; injectable biomaterials; mesenchymal stem cell; vasculogenesis