Sustained release of basic fibroblast growth factor and angiogenesis in a novel covalently crosslinked gel of heparin and alginate

The construction of organs by tissue engineering and regenerative engineeri ng, using an artificial extracellular matrix, is an innovative method that is expected to replace artificial organs and organ transplantation. We have produced an artificial extracellular matrix of alginate and demonstrated t hat the matrix stimulated the regeneration of skin, nerve, and bone. In thi s report, the new matrix, which consists of heparin and alginate covalently crosslinked with ethylenediamine, was produced to stabilize and control th e release of growth factors. Heparin content of the new matrix was confirme d by toluidine blue absorption, elementary analysis, and Fourier transform infrared spectrum. In vitro experiments showed that the new matrix signific antly suppressed the initial burst of basic fibroblast growth factor, which :is a representative member of heparin-binding growth factors, and released biologically active basic fibroblast growth factor for 1 month under physi ological conditions. Obvious cellular infiltration and and angiogenesis wer e shown to occur in the new matrix which was implanted subcutaneously in th e dorsal area of rat with 1 mug of basic fibroblast growth factor for 2 wee ks. This new matrix may be useful for not only the construction of transpla ntable blood vessels of small diameter, but also the induction of angiogene sis in regenerated skin constructed by tissue Engineering. (C) 2001 John Wi ley & Sons, Inc. J Biomed Mater Res 56: 216-221, 2001.