Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

Abstract

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering.

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

“…Although local injection techniques have the advantage of precise delivery of injectate to the target, less invasive techniques, such as use of intrathecal injections or scaffolds, could be considered for treatment delivery. Scaffolds not only provide guidance and orientation of axons after injury [57,58], but extended release scaffolds also can be loaded with substances [59] and should be considered as a less invasive method for intraparenchymal drug delivery.…”

c-Jun Gene-Modified Schwann Cells: Upregulating Multiple Neurotrophic Factors and Promoting Neurite Outgrowth

“…5,6 Nerve conduits (NCs) have been developed as an attractive alternative because they can restore the nerve pathway (which is a prerequisite for successful regeneration) while avoiding the disadvantages of autologous transplants. [7][8][9] NCs have been applied in a clinical setting and have been reported to be beneficial for patients. However, the limitations of those conduits soon became evident, including suboptimal functional recovery and a limited transplant distance.…”

Enhanced Femoral Nerve Regeneration After Tubulization with a Tyrosine-Derived Polycarbonate Terpolymer: Effects of Protein Adsorption and Independence of Conduit Porosity

“…20 However, when these conduits are used empty in experimental and clinical studies, to treat injuries greater than the critical size, [21][22][23] nerve regeneration and functional recovery are significantly impaired as compared to autografts. 11,[24][25][26][27] Ongoing issues, such as swelling that can occlude the inner lumen, inappropriate degradation rates, and cytotoxic degradation products, are believed to be associated with inhibiting regeneration. 2,9,[28][29][30] To meet the ongoing need for an optimal material for nerve conduits, we are exploring the library of tyrosinederived polycarbonates.…”