Japanese Researchers Successfully Use 3D Printed Conduits for Nerve Regeneration in Rats

A team of 13 Japanese researchers led by Kyoto University’s Department of Orthopaedic Surgery professor Ryosuke Ikeguchi successfully tested the efficacy of 3D printed conduits in nerve regeneration.

Various diseases, bacterial infections and physical injuries can lead to peripheral neuropathy, a disorder which limits signals of the human brain, spinal cord and central nervous systems from reaching body parts and internal organs. Severe peripheral neuropathy could restrict an individual’s ability to walk, move body parts and digest, which may lead to other diseases if not prevented and treated.

Currently, the vast majority of health care centers, hospitals, surgeons and doctors utilize a method called autologous nerve grafting to treat peripheral nerve injuries. Often known as the gold standard for peripheral nervous system clinical treatments, autologous nerve grafting requires surgeons to obtain nerve segments from another part of the body to repair lesion gaps in the nervous system. The nerve segments or tissues are taken from the same individual, hence the term autologous.

Figure 1 from the paper: A: The pre-designed 3D tube-like structure. The green spheres represent homogeneous multicellular spheroids that were developed using only human normal dermal fibroblasts. B: The Bio 3D conduit according to the pre-designed 3D model. The conduit was cannulated via a 18-gauge intravenous catheter (SURFLO: NIPRO, Osaka, Japan). Scale bar = 10 mm.

In most cases, autologous nerve grafting turns out to be successful, as noted by Larry M. Wolford. It holds a high success probability rate in contrast to many major surgical procedures. However, if surgeons are unable to remove nerve tissues or segments from the patient’s body for many reasons, the patient is then required to find donors who are willing to supply their tissues. In some cases, when patients fail to find these donors or aren’t in a financial situation to afford the procedure, the disease is left untreated.

Figure 2 from the paper: A: In the Bio 3D group, an 8-mm Bio 3D conduit was interposed into the nerve defect, and the proximal and distal nerve stumps were secured 1.5 mm into the tube to create a 5-mm interstump gap in the conduit. B: In the silicone group, the silicone tube with 8 mm length was interposed in the same procedure.

As an alternative solution, Ikeguchi’s team of researchers tested the efficacy of 3D printed conduits manufactured with high performance and enterprise-grade 3D bioprinters. By using normal human dermal fibroblasts as the base material, Ikeguchi’s team 3D printed scaffold-free conduits to act as nerve tissues.

During the experiment, researchers tested the adaptability of 3D printed conduits in twelve adult male rats. In order to investigate the effect of 3D printed conduits in regenerating nerve tissues and segments, researchers gathered rats with immune deficiency which underwent mid-thigh-level transection of the right sciatic nerve. In a similar process to autologous nerve grafting, instead of using tissue segments from the test rats, researchers utilized the 3D printed conduits to connect lesion gaps of the rats.

In the second phase of the experiment, researchers gathered data from the group of rats which were treated with 3D printed conduits and compared it to a group of rats which were treated with silicone tubes. After comparing the two groups, researchers discovered in a series of electrophysiological studies that the group of rats treated with 3D printed conduits demonstrated significantly higher compound muscle action potential.

Figure 5 from the study: A: Regenerated sciatic nerve eight weeks after surgery in the Bio 3D group. B: In the silicone group, the nerve gap was bridged, however the regenerated nerve was very thin in the silicone tube. Scale bar = 5mm.

Researchers stated:

“We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.”

Previously, 3DPrint.com reported that a British patient by the name of Edward Evans was treated by the Commonwealth Scientific and Industrial Research Organization (CSIRO) of Australia with a 3D printed titanium and polymer sternum. CSIRO revealed that the utilization of 3D printing technology led to faster and more efficient recovery. Ryosuke Ikeguchi and his team also concluded that the utilization of 3D printed conduits led to better adaptation and recovery of rats, demonstrating the flexibility of 3D printing technology in complex clinical procedures. Research into 3D printing and nerve repair has been ongoing for some years now around the world as researchers strive to put the technology to use in complex applications.

All of the researchers involved in the study: Hirofumi Yurie, Ryosuke Ikeguchi, Tomoki Aoyama, Yukitoshi Kaizawa, Junichi Tajino, Akira Ito, Souichi Ohta, Hiroki Oda, Hisataka Takeuchi, Shizuka Akieda, Manami Tsuji, Koichi Nakayama, Shuichi Matsuda. The paper, “The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model,” can be read in full here. Discuss in the Kyoto University forum at 3DPB.com.