A basic fibroblast growth factor slow‐release system combined to a biodegradable nerve conduit improves endothelial cell and Schwann cell proliferation: A preliminary study in a rat model

Abstract

Background A basic fibroblast growth factor (bFGF) slow‐release system was combined to a biodegradable nerve conduit with the hypothesis this slow‐release system would increase the capacity to promote nerve vascularization and Schwann cell proliferation in a rat model. Materials and Methods Slow‐release of bFGF was determined using Enzyme‐Linked ImmunoSorbent Assay (ELISA). A total of 60 rats were used to create a 10 mm gap in the sciatic nerve. A polyglycolic acid‐based nerve conduit was used to bridge the gap, either without or with a bFGF slow‐release incorporated around the conduit (n = 30 in each group). At 2 (n = 6), 4 (n = 6), 8 (n = 6), and 20 (n = 12) weeks after surgery, samples were resected and subjected to histological, immunohistochemical, and transmission electron microscopic evaluation for nerve regeneration. Results Continuous release of bFGF was found during the observation period of 2 weeks. After in vivo implantation of the nerve conduit, greater endothelial cell migration and vascularization resulted at 2 weeks (proximal: 20.0 ± 2.0 vs. 12.7 ± 2.1, P = .01, middle: 17.3 ± 3.5 vs. 8.7 ± 3.2, P = .03). Schwann cells showed a trend toward greater proliferation and axonal growth had significant elongation (4.9 ± 1.1 mm vs. 2.8 ± 1.5 mm, P = .04) at 4 weeks after implantation. The number of myelinated nerve fibers, indicating nerve maturation, were increased 20 weeks after implantation (proximal: 83.3 ± 7.5 vs. 53.3 ± 5.5, P = .06, distal: 71.0 ± 12.5 vs. 44.0 ± 11.1, P = .04). Conclusions These findings suggest that the bFGF slow‐release system improves nerve vascularization and Schwann cell proliferation through the biodegradable nerve conduit.

A clinical multi‐center registry study on digital nerve repair using a biodegradable nerve conduit of PGA with external and internal collagen scaffolding

“…Besides biodegradable nerve conduit, a search for use of decellularized allogenic nerve matrix seeded with bone marrow derived mesenchymal stem cells has been explored by bridging a 20 mm sciatic nerve gap in rats (Kaizawa et al, ). Moreover, biodegradable nerve conduits have been greatly developed with growth factors in the past decades, which includes our recent experiment on the biodegradable nerve conduit with a basic fibroblast growth factor slow‐release system (Fukuda, Kusuhara, Nakagoshi, Isogai, & Sueyoshi, ). Basic fibroblast growth factor (bFGF) is a cytokine that accelerates angiogenesis (Gospodarowicz, ).…”

“…bFGF‐gelatin microsphere complex is released slowly according to the degradation speed of gelatin and the pharmacological activity of bFGF can therefore be maintained for 2 weeks (Tabata et al, ). The in vivo study using the nerve conduit with bFGF slow‐release system demonstrated that the migration distance for both vascular endothelial cells and Schwann cells, and the elongation distance of axons were accelerated in the early phase of nerve regeneration (within 4 weeks after implantation) (Fukuda et al, ). With a growing interest in the clinical potential of mesenchymal stem cells derived from bone marrow (Kaizawa et al, ), adipose tissue (Kappos et al, ; Saller et al, ), and menstrual blood (Farzamfar et al, ), the utilization of these stem cells into biodegradable nerve conduits with FGF slow‐release system may offer a promising technique to enhance nerve regeneration with biodegradable nerve conduits.…”

Repair of facial nerve crush injury in rabbits using collagen plus basic fibroblast growth factor

“…It is well known that an adequate blood supply is important to nerve regeneration (Tassi et al, 2001). bFGF is a cytokine that accelerates angiogenesis (Gospodarowicz, 1991) and contributes to the proliferation of undifferentiated SCs (Fukuda, Kusuhara, Nakagoshi, Isogai, & Sueyoshi, 2018;Li et al, 2017). So more vascular regeneration stimulated, more SCs will migrate to nerve injury area through the blood vessels and dedifferentiate to a stem-like cell, which is benefit for nerve regeneration.…”

Machine intelligence for nerve conduit design and production

“…It is thought that one of the limiting factors is the ability to supply enough nutrients and oxygen to facilitate axon growth. Research has shown that vascular networks within NGCs can be enhanced in the early post-transplantation period by including vascular bundles in the graphs [127]. Consequently, increased vascularity of nerve grafts has been demonstrated to improve overall nerve regeneration and axonal elongation [128,129].…”