Silk Fibroin-Based Scaffolds with Controlled Delivery Order of VEGF and BDNF for Cavernous Nerve Regeneration

Abstract

To investigate the synergistic effect of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) on cavernous nerve regeneration, two different aligned scaffolds consisting of coaxial electrospun silk fibers were prepared by switching the position of the two factors in either core or shell domain. The order and release rate of the dual factors delivery were relatively different because of the distinct location of two factors in coaxial fibers. An in vitro assay showed that the inner-VEGF/outer-BDNF scaffolds could more obviously accelerate Schwann cells growth, proliferation and spreading owing to the rapid release of BDNF. However, in vivo scaffold implantation demonstrated that the inner-BDNF/outer-VEGF scaffolds significantly facilitated more angiogenesis, and promoted more nerve regeneration based on great benefit of angiogenesis. Results showed that the reasonable dual-delivery order of VEGF and BDNF from scaffolds could enhance synergistic effect of the factors and promote cavernous nerve regeneration.

Electrospun Nanofibers for Improved Angiogenesis: Promises for Tissue Engineering Applications

“…Indeed, the orientation and growth of axons can be guided by aligned nanofibrous matrices in order to allow for the formation of a vascularized network [273]. Zhang et al investigated the neural regeneration capacity of coaxial electrospun silk fibers loaded with VEGF and brain-derived neurotrophic factor (BDNF) on cavernous nerve regeneration [274]. Two types of core-shell nanofibrous scaffolds were produced and designated as IVOB (inner layer-2.84 × 10 −1 ng/mg of VEGF/outer layer-5.80 × 10 −1 ng/mg of BDNF) and IBOV (inner layer-2.84 × 10 −1 ng/mg of BDNF/outer layer-5.80 × 10 −1 ng/mg of VEGF).…”

“…The histopathological results confirmed more nerve regeneration based on promoted angiogenesis in the inner-BDNF and outer-VEGF scaffolds compared with the inner-EGF and outer-BDNF, owing to faster release of VEGF following 8 weeks post-implantation ( Figure 5). Adapted from Zhang et al [274], with permission from American Chemical Society.…”

“…( B ) Immunohistochemistry (IHC) staining of the harvested samples for evaluating new vessels in the retrieved scaffolds of RSF-neat, inner-VEGF/outer-brain-derived neurotrophic factor (BDNF) (IVOB), and inner-BDNF/outer-VEGF (IBOV) after 4 and 8 weeks of implantation (a), in which the asterisk (*) shows the scaffold fragments and the yellow arrows show vessels (bar: 100 μm); and (b) graph showing the vessel densities in (a) in which the asterisk (*) shows significant differences among the groups at each time point ( p < 0.05). Adapted from Zhang et al [ 274 ], with permission from American Chemical Society.…”

Water‐insoluble amorphous silk fibroin scaffolds from aqueous solutions

“…Regenerated silk fibroin (RSF), derived from the silkworm cocoon, is a useful biomaterial as a cell‐support matrix for osteoblasts, endothelial cells, nerve cells and various stem cells, as a scaffold for bone, cartilage, muscle, blood vessels, skin and nerves, and as a carrier for hydrophilic and hydrophobic drugs and growth factors (Chen, Chen, Kuo, Li, & Chen, ; Crivelli et al, ; Farè et al, ; Font Tellado et al, ; Font Tellado et al, ; Hennecke et al, ; Jo et al, ; Kundu, Rajkhowa, Kundu, & Wang, ; Le, Liaudanskaya, Bonani, Migliaresi, & Motta, ; Moses, Nandi, & Mandal, ; Musson et al, ; Sell, McClure, Ayres, Simpson, & Bowlin, ; Teuschl et al, ; Woloszyk, Buschmann, Waschkies, Stadlinger, & Mitsiadis, ; Y. P. Zhang et al, ). Besides the inherent virtues of silk fibroin, such as biocompatibility, a green formation process, and tunable biodegradability, another feature is its diversity of conformations, hierarchical microstructures and various material states, endowing the possibility of designing biomaterials with selective and useful performance (Gorenkova et al, ; Hu et al, ; Kumar, Nandi, Kaplan, & Mandal, ; Qi et al, ; Rockwood et al, ).…”

Tailoring degradation rates of silk fibroin scaffolds for tissue engineering

“…The SF with controlled degradation rate makes it advantageous for developing the next generation scaffolds degraded gradually along with the tissue regeneration . Despite the biocompatibility and degradation of regenerated SF have been well established, the in vivo SF scaffold behavior with controlled biodegradation rate prepared from regenerated SF solutions has not been fully demonstrated …”