Novel heparin/alginate gel combined with basic fibroblast growth factor promotes nerve regeneration in rat sciatic nerve

Abstract

We have developed an alginate gel crosslinked with covalent bonds for regeneration of dermis, nerve, and bone. Recently, a novel matrix (H/A gel) which consists of heparin and alginate covalently crosslinked with ethylenediamine, was designed. It can stabilize and release biologically active basic fibroblast growth factor (bFGF) for 1 month, which is one of the heparin-binding growth factors. In the present report, we examined the effect of this novel H/A gel on nerve regeneration in the rat sciatic nerve. In this study, regenerated axons in H/A gel with bFGF grew faster than in ordinary alginate gel with bFGF in the early stage. Myelinated fibers showed a tendency to increase in diameter toward the normal size in the later stage. Nerve bundles in the implantation exhibited minimal fibrosis and good vascularization. H/A gel with bFGF exhibited better-developed vascularization than ordinary alginate gel with bFGF. These findings suggested that H/A gel with bFGF could serve not only as an efficient cellular scaffold, but also as a stabilizing matrix for bFGF for peripheral nerve regeneration.

Manipulation of hydrogel assembly and growth factor delivery via the use of peptide–polysaccharide interactions

“…The utility of the assembled heparinized hydrogels in this kind of application is suggested by the fact that heparin binds bFGF to form a stable complex [47,48]. The complex maintains the biological activity of bFGF [49] and can retard bFGF release from polymeric materials [50,51]. Although covalently crosslinked, heparin-containing hydrogels have been shown to be useful for release of bFGF [52], physically cross-linked hydrogels could provide an alternative protein-delivery matrix without the need for potentially toxic crosslinking reagents.…”

Custom Design of the Cardiac Microenvironment With Biomaterials

“…In contrast, biomaterials designed to deliver proteins and foster cell growth use protein binding sites for delivery ( Figure 1). Some proteins such as platelet-derived growth factor and fibroblast growth factor-2 have domains that bind extracellular matrix proteins or highly charged materials and limit diffusion, 30,31 whereas other proteins like IGF-1 diffuse more rapidly. Kanematsu et al incorporated a variety of different growth factors into collagenous matrices 32 and found very different release profiles from the matrices both in vitro and in vivo, with rapid loss of IGF-1 compared with other factors.…”

Mesenchymal Stem Cells and Umbilical Cord as Sources for Schwann Cell Differentiation: their Potential in Peripheral Nerve Repair

“…Many approaches have been used in an attempt to restore neural function. Recent tissue engineering researches have focused on the development of bioartificial nerve conduits aimed at guiding axonal regrowth [14,15]. In this system, the nerve ends and intervening gap are enclosed within a tube composed of biologic or synthetic materials, thereby allowing axons to regrow into the distal nerve segment [16].…”