Biomaterials

Based on the haptotactic (cell binding) properties of fibrin, we have conducted extensive studies on the cell binding properties of fibrinogen and developed new Fibrin-based dense dehyrothermally crosslinked biodegradable Microbeads (FMB) for culturing high density of cells in suspension for their implantation. The FMB can attract and carry high number of matrix dependent cells of different types and can be used to culture stromal cells of different origin including fibroblasts, placental cells, endothelial cells, smooth muscle cells, chondrocytes and osteoblasts as well as endothelial cells. We employed FMB to isolate mesenchymal pluripotent stem cells from bone marrow and cord blood to expand them in vitro, and to induce differentiation in vitro or to implant as progenitors cells to produce cartilage and bone tissues. In parallel studies on the mechanism of cell binding to fibrin we identified new family of ~20mer epitopes on fibrinogen that seem to be responsible for the selective haptotactic activity of fibrin based matrices. Synthetic peptides of these sequences on a matrix could be used to augment cell binding to matrices in tissue engineering. The family of the short haptotactic peptidic sequences, which were termed haptides were also investigated as potent cell penetrating agents following fibrinolysis, as well as non-immunogenic synthetic cell penetrating sequences. The possible systemic adverse effects of penetrating peptides as well as fibrin derived haptides were also investigated in parallel.

 

 

 

Recent Publications:

 

1. Raphael Gorodetsky, Shainer R, Gaberman E, Levdansky L and  Gorodetsky R (2010) Efficient isolation and chondrogenic differentiation of adult mesenchymal stem cells with fibrin microbeads and micronized collagen sponges. Regen. Med. 5(2): 255-65.
2. Raphael Gorodetsky, Levy-Beladev L, Levdansky L, Gaberman E, Benyamini H and  Friedler A (2010) A family of cell adhesion peptides homologous to fibrinogen C-terminals. Biochemical and Biophysical Research Communications 401: 124-130.
3. Raphael Gorodetsky, Basheer, M Schwalb H, Nesher M, Gilon D Shefler I, Mekori, J A Shara O M (2010) Mast cell activation by fibrinogen-related homologous c-terminal peptides (haptides) modulates systemic blood   pressure. J Allergy Clin Immunol 126:1041-1048.
4. Raphael Gorodetsky, Basheer M, Schwalb H, Shefler I, Levdansky L T, Mekori JA, Gorodetsky R (2011) Blood pressure modulation following activation of mast cells by cationic cell penetrating peptides. Peptides 32 (12): 2444-2451.
5. Raphael Gorodetsky, Xie M W, Gorodetsky Ro, Micevicz E, Mackenzie N C, Gaberman E, Levdansky L and McBride W Ho (2013) Marrow stromal cells delivery on fibrin microbeads can correct radiation-induced wound healing deficits. Journal of Investigative Dermatology 133 (2): 553-561.