Effects of fibrin micromorphology on neurite growth from dorsal root ganglia cultured in three-dimensional fibrin gels

Abstract

The effect of fibrin matrix micromorphology on neurite growth was investigated by measuring the length of neurites growing in three-dimensional fibrin gels with well characterized micromorphologies. Dorsal root ganglia (DRGs) from 7-day chick embryos were entrapped and cultured in gels made from varying concentrations of fibrinogen (5-15 mg/mL) or calcium (2-10 mM). The length of growing neurites was measured with light videomicroscopy, and the number and diameter of fibrin fiber bundles were measured from scanning electron micrographs. An increase in fibrinogen concentration caused a decrease in the average fiber bundle thickness, an increase in the number of fiber bundles, and a marked decrease in neurite length. Gels made with different calcium concentrations had a similar range of variation in fibrin fiber bundle number or diameter, but these variations had little effect on neurite and associated nonneuronal cell outgrowth. These results provide insights into the process of neurite advance within fibrin and may be useful in the design 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 polymerization do not accurately predict fibrin structure at these higher concentrations.

Prosthetic vascular grafts: Wrong models, wrong questions and no healing

“…While a fibrin matrix strongly stimulates angiogenesis at lower fibre density [163], it inhibits capillary formation at higher fibre density. A similar inverse correlation between cell growth and fibre density was found on an ultrastructural level [162]. The higher the density of fibrin fibres and the lower the average thickness of these fibre bundles was, the lower was its penetrability for cells [162].…”

“…In contrast, the continual replenishment of clotting factors and calcium from the blood surface create conditions where thinner and much denser fibres, which are inhibitory for vessel ingrowth, are being formed, Furthermore, continual platelet replenishment and degranulation makes this fibrin rich in TGF-b, which at high release-concentrations is additionally inhibitory to capillary formation. a decrease in fibre bundle thickness and an increase in fibre bundle density [162]. While a fibrin matrix strongly stimulates angiogenesis at lower fibre density [163], it inhibits capillary formation at higher fibre density.…”

Cell encapsulation using biopolymer gels for regenerative medicine

“…Despite this, when the neurons encapsulated in the HA gels were implanted, there was no restoration of spinal cord function. Herbert et al (1998) also investigated the use of fibrin gels for neural tissue engineering. Encapsulated chick dorsal root ganglia were successfully maintained in the hydrogels and displayed neutrite outgrowth.…”

Composite Fibrin Scaffolds Increase Mechanical Strength and Preserve Contractility of Tissue Engineered Blood Vessels

“…Previous work demonstrated that increasing the fibrinogen (FBG) concentration increased the number of fiber bundles at the expense of fiber bundle thickness (33). To examine the effects of these structural changes on mechanical properties, we measured the ultimate tensile force (UTF) and burst pressure of cylindrical, cell-free fibrin hydrogels as a function of FBG concentration.…”