The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model

Abstract

BackgroundAlthough autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit.MethodsWe developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery.ResultsKinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01).ConclusionsWe confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

Biomimetic neural scaffolds: a crucial step towards optimal peripheral nerve regeneration

“…129 Yurie et al further confirmed in rats that 3D printed conduits promoted nerve regeneration. 130 Many reports have shown that 3D printing technology provides an exciting new fabrication technique that may be able to fulfill clinical needs for complicated and patient-specific artificial nerve grafts which cannot be satisfied by conventional fabrication techniques. Despite exciting preclinical results, 3D printing technology is still relatively new and largely unvalidated clinically.…”

A scaffold‐free Bio 3D nerve conduit for repair of a 10‐mm peripheral nerve defect in the rats

“…A “Bio‐3D printer (Regenova®, Cyfuse, Tokyo, Japan)” can fabricate tubular materials such as vessels (Itoh, Nakayama, Noguchi, et al, ), tracheae (Taniguchi, Matsumoto, Tsuchiya, et al, ), and nerve conduits (Yurie, Ikeguchi, Aoyama, et al, ; Zhang et al, ) exclusively from cells without added foreign materials. The Bio 3D nerve conduit was fabricated by placing spheroids, which were generated from normal human dermal fibroblasts, into a needle array to form a tubular structure using a “Bio‐3D printer.” Biomaterial was not used during its fabrication.…”

“…We previously reported that nerve regeneration was promoted by a Bio 3D printed nerve conduit without cytotoxic inflammation; the substantial cellular composition and presence of ECM components aided the regenerative process through its biocompatibility. However, only a 5 mm nerve gap length was reported to be regenerated with a Bio 3D printed nerve conduit (Yurie et al, ; Zhang et al, ). The purpose of the present study was to fabricate Bio 3D conduits for a 10 mm nerve gap and to evaluate their capacity for nerve regeneration in a rat sciatic nerve defect model.…”

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

“…[137] Bio 3D printing technique is characterized by developing a complete biological tubular structure, in this case using homogenous fibroblast multicellular spheroids. A pre-designed 3D tube-like structure represents the position of the spheroids that are robotically placed into skewers of a 9×9 needle array Fig.…”

“…4 (A–B). [137] This “needle –array” arrangement promotes multicellular spheroids to fuse and after one week are removed and cultured on bioreactor to obtained a structurally scaffold -free construct. The Bio 3D conduit was evaluated in vivo on rat right sciatic nerve, with a 5-mm gap that was bridged using an 8 mm Bio 3D conduit and control group with silicone tube.…”