Yuji Inada

Artificial nerve tubes and their application for repair of peripheral nerve injury: an update of current concepts

SUMMARYnOver the last 20 years, an increasing number of research articles have reported on the use of artificial nerve tubes to repair nerve defects. The development of an artificial nerve tube as an alternative to autogenous nerve grafting is currently a focus of interest for peripheral nerve repair. The clinical employment of tubes as an alternative to autogenous nerve grafts is mainly justified by the limited availability of donor tissue for nerve autografts and the related morbidity. Numerous studies indicate that short-distance defects in humans can be successfully treated by implantation of artificial nerve guides. This review provides a brief overview of various preclinical and clinical trials conducted to evaluate the utility of artificial nerve tubes for the regeneration of peripheral nerves. This review is also intended to help update hand surgeons on the rapid advances in tubulization techniques, and to provide them with indications of the various directions toward which future research can proceed. Future studies need to provide us with as much comparative information as possible on the effectiveness of different tubulization techniques, in order to guide the surgeon in choosing the best indications for their optimal clinical employment. Future progress in implant development can be expected from interdisciplinary approaches involving both materials and life sciences, leading to advances in neuro-tissue engineering that will be needed to effectively treat larger nerve defects.

Experimental study on the regeneration of peripheral nerve gaps through a polyglycolic acid–collagen (PGA–collagen) tube

We have developed a bioabsorbable polyglycolic acid (PGA) tube filled with collagen sponge (PGA-collagen tube) as a nerve connective guide, and compared its effectiveness with that of autograft in terms of nerve regeneration across a gap. The PGA-collagen tube was implanted into 24 beagle dogs across a 15-mm gap in the left peroneal nerve. The right peroneal nerve was reconstructed with the autograft harvested from the left side, as a control. After the surgery, the connective tissue extended from both cut ends in the PGA-collagen tube and connected again at the center. Pathologically, the collagen sponge in the tube provided adequate scaffolding for nerve tissue extension, and the nerve tissue reconnected within 3 weeks. Electrophysiologically, muscle-evoked potentials (MEPs) and compound nerve action potentials (CNAPs) were detected 18 days after the surgery. For up to 6 months postsurgery, CNAPs and somatosensory-evoked potentials (SEPs) on the PGA-collagen side had a shorter latency and larger peak voltage than those on the autograft side. The myelinated axons on the PGA side were larger in diameter than those on the autograft side. It is suggested that the PGA-collagen tube has the potential to be an effective alternative to conventional autografting for the repair of some peripheral nerve defects.

Regeneration of peripheral nerve gaps with a polyglycolic acid-collagen tube

OBJECTIVE:The aim of this study was to report by means of objective methods on the effectiveness of a nerve reconstruction procedure using a bioresorbable tube in two patients. Our previous successes in regenerating canine peripheral nerves across long distances (80-mm gaps) using a bioabsorbable tube have led us to investigate the value of such a tube for the treatment of human patients with chronic nerve injuries. METHODS:The device was made from a cylindrically woven polyglycolic acid tube filled with a collagen sponge. It was designed to be resorbed after nerve regeneration. Peripheral sensory nerve defects in two patients with neuroma and pain were reconstructed using this tube. Patient 1 (a 62-year-old man) had a 20-mm defect of the proper digital nerve, and Patient 2 (a 56-year-old woman) had a 65-mm defect of the superficial peroneal nerve. RESULTS:After surgery, both patients recovered from the unpleasant sensations and intolerable pain. In Patient 1, functional recovery was objectively identified at 2 months, and conduction velocity of the nerve recovered to 49.1 m/s. In Patient 2, conduction velocity of the nerve was determined to be 16.9 m/s at 5 months. Current perception threshold testing indicated that sensory nerve function had been recovered by 65 days after surgery. CONCLUSION:This work represents the first precise clinical evaluation, performed under objective evaluation criteria, of sensory recovery achieved using a nerve tube, suggesting that the use of a polyglycolic acid-collagen tube has the potential to become a viable alternative to conventional autografting for the repair of peripheral nerve defects.

Surgical relief of causalgia with an artificial nerve guide tube: Successful surgical treatment of causalgia (Complex Regional Pain Syndrome Type II) by in situ tissue engineering with a polyglycolic acid-collagen tube

&NA; Two patients with causalgia associated with allodynia and finger contracture were treated surgically with a bioresorbable nerve guide tube made from polygycolic acid and collagen: the injured segment of the digital nerve was resected and the resulting gap (25 and 36 mm) was bridged with the tube. In both cases, a neuroma was found on the injured nerve and many sprouting branches were. After reconstruction, the causalgia and allodynia disappeared and movement of the fingers recovered during the following 6 months. Functional recovery was objectively identified for 1 year and 9 months. Both patients regained full use of their finger and were free of discomfort for up to 24 and 18 months, respectively. Since the first description of causalgia in 1864, there has been no definitive treatment for this intractable burning pain. Our experience shows that at least some types of causalgia can be resolved successfully by surgery.

In situ tissue engineering for tracheal reconstruction using a luminar remodeling type of artificial trachea.

BACKGROUNDnAfter successful trials of tracheal reconstruction using mesh-type prostheses in canine models, the technique has been applied clinically to human patients since 2002. To enhance tissue regeneration, we have applied a new tissue engineering approach to this mesh-type prosthesis.nnnMETHODSnThe prosthesis consists of a polypropylene mesh tube reinforced with a polypropylene spiral and atelocollagen layer. The cervical tracheas of 18 beagle dogs were replaced with the prosthesis. The collagen layer was soaked with peripheral blood in 6 of the dogs, with bone marrow aspirate in another 6, and with autologous multipotential bone marrow-derived cells (mesenchymal stem cells) in another 6. The dogs were humanely killed at 1 to 12 months after the operation.nnnRESULTSnAll 18 dogs survived the postoperative period. Bronchoscopically, 3 of 4 dogs in the peripheral blood group showed stenosis, whereas no stenosis was evident in all 8 of the dogs in the bone marrow and mesenchymal stem cell groups 6 months after the operation. Faster epithelialization and fewer complications, such as mesh exposure and luminal stenosis, were observed in these two groups than in the peripheral blood group. Histologically, the cells from autologous bone marrow were found to proliferate into the tracheal tissue during the first month. Cilial movement in these two groups was faster than that in the peripheral blood group and recovered to 80% to 90% of the normal level.nnnCONCLUSIONSnBone marrow aspirate and mesenchymal stem cells enhance the regeneration of the tracheal mucosa on this prosthesis. This in situ tissue engineering approach may facilitate tracheal reconstruction in the clinical setting.

Regeneration of peripheral motor nerve gaps with a polyglycolic acid-collagen tube: technical case report.

OBJECTIVEAfter previous success in regenerating canine peripheral nerves over 80 mm gaps using a bioabsorbable nerve guide tube, we have extended this method to the treatment of patients experiencing various types of nerve injury. This report describes the treatment of two cases of motor nerve disorder. METHODSThe bioabsorbable nerve tube was a cylindrically woven polyglycolic acid (PGA) tube filled with collagen. A peripheral motor nerve defect (the frontalis branch of the facial nerve) was reconstructed using this PGA-collagen tube in two patients who experienced posttraumatic unilateral eyebrow ptosis for 3 months. RESULTSFive months after surgery, both patients regained their ability to voluntarily lift their eyebrows symmetrically. Electrophysiological examination at 5 months revealed recovery of compound muscle action potential and disappearance of distal latency on the affected side. CONCLUSIONThis is the first clinical report of motor nerve recovery achieved using the PGA-collagen nerve guide tube. The results suggest that use of a PGA-collagen tube is a promising option for the repair of motor nerve defects.

Development of New Nerve Guide Tube for Repair of Long Nerve Defects

A novel nerve guide tube (poly (L-lactic) acid (PLLA)/ polyglycolic acid (PGA)-c-tube) capable of repairing long peripheral nerve injuries in a canine model has been developed. The tube was created by braiding together PLLA and PGA and then coating it with collagen. PLLA was newly added to the formulation to achieve higher sustainability. The tube was compared with a PGA-collagen tube in clinical use since 2002 having the same structure with a collagen coating but composed of PGA alone (PGA-c-tube). When tested for repair of a 40-mm gap in the left peroneal nerve, using PLLA/PGA-c-tube (n = 15), PGA-c-tube (n = 15), and a negative control group where the cut stump was capped using a silicone cap (n = 15), the lumen structure essential for securing the space for nerve regeneration was maintained in PLLA/PGA-c-tube for over 12 months with a higher number of axons both within the tube and at the distal nerve end. Electrophysiological evaluation revealed that the amplitude of compound muscle action potentials and sensory nerve action potentials after nerve regeneration with PLLA/PGA-c-tube were significantly higher. When assessed using magnetic resonance imaging (MRI), the volume of the tibialis anterior (TA) muscle in dogs that had undergone nerve repair using PLLA/PGA-c-tube was approximately 80% that of the positive control at 12 months. Functional analysis conducted by assessing the ankle angle revealed faster recovery in the PLLA/PGA-c-tube group. Better regeneration was achieved using a PLLA/PGA-c-tube that contains the slowly decomposing fiber material, PLLA. This indicates potential for repair of even longer nerve gaps or defects located near joints, and also clinical application.

Arteriovenous shunt in digit replantation

From May 1958 to May 1987, 331 digits were replanted successfully with an overall survival rate of 86.2%. Complete success in replantation of amputated fingers requires an accurate anastomoses of both arteries and veins. However, anastomosis between arteries may not be possible in some patients. Since reports that a thumb amputated at the interphalangeal joint area could be successfully replanted by an arteriovenous shunt on the palmar side, we did arteriovenous shunts in four such cases. Two replantations were successful; necrosis developed in the other two patients.

Regeneration of Central Nervous Tissue Using a Collagen Scaffold and Adipose-Derived Stromal Cells

Adipose-derived stromal cells (ASCs) include stem cells, which have the potential to differentiate into a variety of cell lineages. The regeneration of central nerves was examined using ASCs and a collagen scaffold. A cerebral cortex defect (3 × 4 × 3 mm3) was created in the left frontal lobe of 16 male rats. In one group (n = 8), collagen (3 × 4 × 3 mm3) seeded with DiI-labeled ASCs was implanted in the defect. In order to seed the ASCs, a combination of the rotary cell culture system and pressing the collagen scaffold gently several times with a glass rod was applied. In the control group (n = 8), collagen was implanted without ASCs. The rats were sacrificed at 1 month after the scaffold implantation. Histologically, 0.2% of the implanted ASCs were positive for anti-human/rat microtubule-associated protein 2 (MAP2) antibody and microvessels were present at a density of 4.6 ± 1.2/mm2 within the collagen scaffold-implanted area in each coronal section. In the control group, no MAP2-positive cells were detected and the microvessel density was 0.6 ± 0.4/mm2. These data suggest that ASCs seeded into a collagen scaffold may have the potential to promote regeneration of nervous tissue after cerebral cortex injury.

Blood flow through prefabricated flaps—an experimental study in rabbits

Prefabricated flaps were created by femoral vessel implantation beneath the abdominal skin in rabbits. The area of survival and blood flow through the prefabricated flap were measured after 1, 2, 4, 6, 8, and 12-week intervals. The parameters at 6, 8 and 12-week intervals were significantly larger than those for random pattern flaps (p < 0.01), but were significantly smaller than those for axial pattern flaps (p < 0.01). The minimum interval at which the prefabricated flap could be transferred successfully was between 6 and 8 weeks in this model. Microangiography demonstrated that neovascularisation began at the distal end of the implanted vascular bundle and spread throughout the flap by 8 weeks.