title: Fibrin microbeads (FMB) as biodegradable carriers for culturing cells and for accelerating wound healing.
abstract: We have developed biodegradable fibrin-derived microbeads as potent cell carriers. The fibrin-derived microbeads, 50-200 microm in diameter, were tested for their attachment to a wide range of cell types. Fibrin-derived microbeads were shown to be greatly haptotactic to cells (such as endothelial cells, smooth muscle cells and fibroblasts), which respond to fibrinogen in contrast to keratinocytes and different cell lines derived from leukocytic lineage. The cells on fibrin-derived microbeads could be maintained for more than 10 d and achieved a high density. 31P-nuclear magnetic resonance was employed to monitor phosphate metabolism in cells, with densities on the order of 100 million cells per g of fibrin-derived microbeads. The 31P-nuclear magnetic resonance adenosine triphosphate and phosphocreatine signals, equivalent to the signal obtained with perfused normal skin, indicated that metabolism of cells on fibrin-derived microbeads was responsive to oxygenation and nutrients. Light, fluorescent, and confocal laser microscopy revealed that the porous fibrin-derived microbeads accommodate up to 200-300 cells due to their high surface area which minimized contact inhibition. Cells could degrade the fibrin-derived microbeads and be transferred to seed culture flasks without trypsinization. In a pig skin wound healing model, fibrin-derived microbeads + fibroblasts were transplanted into full thickness punch wounds. This procedure was compared with other treatment modalities, such as the addition of human platelet-derived growth factor BB or fibrin-derived microbeads alone. By the third day after wounding, only the wounds in which fibroblasts on fibrin-derived microbeads were added showed significant formation of granulation tissue. Based on the above, we project many uses of our novel fibrin-derived microbead technology for cell culturing, wound healing and tissue engineering.
authors.affiliation: Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Gorodetsky
authors.forename: R A
authors.initials: RA
authors.lastname: Clark
authors.forename: J
authors.initials: J
authors.lastname: An
authors.forename: J
authors.initials: J
authors.lastname: Gailit
authors.forename: L
authors.initials: L
authors.lastname: Levdansky
authors.forename: A
authors.initials: A
authors.lastname: Vexler
authors.forename: E
authors.initials: E
authors.lastname: Berman
authors.forename: G
authors.initials: G
authors.lastname: Marx
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental / Q000187:drug effects; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D017690:Cell Transplantation / Q000379:methods*; D004727:Endothelium / Q000166:cytology; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000637:transplantation; D006097:Granulation Tissue / Q000502:physiology; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008863:Microspheres; D008954:Models, Biological; D009130:Muscle, Smooth / Q000166:cytology; D010759:Phosphorus Isotopes; D012867:Skin / Q000293:injuries; D013552:Swine; D014945:Wound Healing / Q000502:physiology*
chemical_list: D010759:Phosphorus Isotopes; D005337:Fibrin; D005340:Fibrinogen