EFFECTS OF FIBRIN MICROMORPHOLOGY ON NEURITE GROWTH FROM DORSAL-ROOT GANGLIA CULTURED IN 3-DIMENSIONAL FIBRIN GELS

The effect of fibrin matrix micromorphology on neurite growth was inve stigated by measuring the length of neurites growing in three-dimensio nal fibrin gels with well characterized micromorphologies. Dorsal root ganglia (DRGs) from 7-day chick embryos were entrapped and cultured i n gels made from varying concentrations of fibrinogen (5-15 mg/mL) or calcium (2-10 mM). The length of growing neurites was measured with li ght videomicroscopy, and the number and diameter of fibrin fiber bundl es were measured from scanning electron micrographs. An increase in fi brinogen concentration caused a decrease in the average fiber bundle t hickness, an increase in the number of fiber bundles, and a marked dec rease in neurite length. Gels made with different calcium concentratio ns had a similar range of variation in fibrin fiber bundle number or d iameter, but these variations had little effect on neurite and associa ted nonneuronal cell outgrowth. These results provide insights into th e process of neurite advance within fibrin and may be useful in the de sign of fibrin-based materials used for peripheral nerve regeneration. Furthermore, this study provides the first detailed experimental data on the micromorphology of fibrin matrices made from more than 5 mg/mL of fibrinogen and indicates that existing kinetic models of fibrin po lymerization do not accurately predict fibrin structure at these highe r concentrations. (C) 1998 John Wiley & Sons, Inc.