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 engineering, 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 that the matrix stimulated the regeneration of skin, nerve, and bone. In this report, the new matrix, which consists of heparin and alginate covalently crosslinked with ethylenediamine, was produced to stabilize and control the release of growth factors. Heparin content of the new matrix was confirmed by toluidine blue absorption, elementary analysis, and Fourier transform infrared spectrum. In vitro experiments showed that the new matrix significantly 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 physiological conditions. Obvious cellular infiltration and angiogenesis were shown to occur in the new matrix which was implanted subcutaneously in the dorsal area of rat with 1 microg of basic fibroblast growth factor for 2 weeks. This new matrix may be useful for not only the construction of transplantable blood vessels of small diameter, but also the induction of angiogenesis in regenerated skin constructed by tissue engineering.