1. Sharett Institute of Oncology, Hadassah University Hospital, Jerusalem, Israel
2. ^*Department of Dermatology, SUNY Medical School, Stony Brook, New York, New York, U.S.A.
3. ^†Vitex Inc, New York, New York, U.S.A.

Correspondence: Dr Raphael Gorodetsky, Sharett Institute of Oncology, Hadassah University Hospital, POB 12000, Jerusalem, 91120, Israel

¹The authors declared conflict of interest. A patent on the method of preparation and commercial uses of FMB is pending.

Received 12 October 1998; Revised 28 December 1998; Accepted 24 February 1999.

Abstract

We have developed biodegradable fibrin-derived microbeads as potent cell carriers. The fibrin-derived microbeads, 50–200 m 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.