Angiogenic potential of silk fibroin-IKVAV peptide hydrogels: in vitro evaluations in co- culture of outgrowth endothelial cells and human mesenchymal stem cells

The design of an instructive niche favoring local angiogenesis might open new possibilities for treating damaged tissues in particular ischemia injury. In this context biomaterial based transplantation strategies and especially injectable hydrogels for cell delivery of endothelial cells could be a promising approach to induce vascularization in critical ischemic areas of the soft tissues, such as brain (1). Sonication-induced hydrogel formation of silk fibroin has been recently investigated in neural tissue engineering (2). Sonication is a physically crosslinking procedure to induce the fast gelation of silk fibroin, which allows the addition of cells post-sonication as well as the injection into the target tissue before gelation. IKVAV peptide, derived from extracellular matrix component laminin, has been proven to be an active site for neural cell adhesion and neurite outgrowth. In addition, IKVAV peptide has also been reported to induce angiogenesis (3). We have investigated if IKVAV peptide modified silk fibroin hydrogels can promote angiogenesis in the mono-culture system of OEC and co-culture system of OEC and BM-MSC. For this purpose, 1% unmodified, IKVAV-modified and control peptide VVIAK-modified silk fibroin hydrogels were prepared and cells were included into the matrix. In the co-culture system with MSC, all hydrogels independent from their modification were able to support angiogenesis and the formation of capillary network formation. Angiogenic potential was also due to the assistance of co-cultured MSCs activity that can secret angiogenic factors such as (VEGF and Ang-1). Thus these hydrogels could be a suitable device to inject cells into local areas suffering from ischemia. References 1. Hudon V, Berthod F, Black AF, Damour O, Germain L, Auger FA. British J. Dermatology, 2003, 148(6), 1094-104. 2. Hopkins AM, De Laporte L, Tortelli F, Spedden E, Staii C, Atherton TJ, et al. Advanced Functional Materials, 2013, 23(41), 5140-9. 3. Nomizu M, Weeks BS, Weston CA, Kim WH, Kleinman HK, Yamada Y. FEBS Letters. 1995, 365(2–3), 227-31.