Artificial nerve graft constructed by coculture of activated Schwann cells and human hair keratin for repair of peripheral nerve defects

Studies have shown that human hair keratin(HHK) has no antigenicity and excellent mechanical properties. Schwann cells, as unique glial cells in the peripheral nervous system, can be induced by interleukin-1β to secrete nerve growth factor, which promotes neural regeneration. Therefore, HHK with Schwann cells may be a more effective approach to repair nerve defects than HHK without Schwann cells. In this study, we established an artificial nerve graft by loading an HHK skeleton with activated Schwann cells. We found that the longitudinal HHK microfilament structure provided adhesion medium, space and direction for Schwann cells, and promoted Schwann cell growth and nerve fiber regeneration. In addition, interleukin-1β not only activates Schwann cells, but also strengthens their activity and increases the expression of nerve growth factors. Activated Schwann cells activate macrophages, and activated macrophages secrete interleukin-1β, which maintains the activity of Schwann cells. Thus, a beneficial cycle forms and promotes nerve repair. Furthermore, our studies have found that the newly constructed artificial nerve graft promotes the improvements in nerve conduction function and motor function in rats with sciatic nerve injury, and increases the expression of nerve injury repair factors fibroblast growth factor 2 and human transforming growth factor B receptor 2. These findings suggest that this artificial nerve graft effectively repairs peripheral nerve injury.

A novel artificial nerve graft for repairing longdistance sciatic nerve defects:a self-assembling peptide nanofiber scaffold-containing poly (lactic-co-glycolic acid) conduit

In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

Artificial facial nerve reflex restores eyelid closure following orbicularis oculi muscle denervation

To date, treatment of peripheral facial paralysis has focused on preservation of facial nerve integrity. However, with seriously damaged facial nerve cases, it is difficult to recover anatomical and functional integrity using present therapies. Therefore, the present study utilized artificial facial nerve reflex to obtain orbicularis oculi muscle （OOM） electromyography signals on the uninjured side through the use of implanted recording electrodes. The implanted electrical chips analyzed facial muscle motion on the uninjured side and triggered an electrical stimulator to emit current pulses, which resulted in stimulation of injured OOM contraction and maintained bilateral symmetry and consistency. Following signal recognition, extraction, and computer analysis, electromyography signals in the uninjured OOM resulted in complete eyelid closure, which was consistent with the voltage threshold for eye closure. These findings suggested that artificial facial nerve reflex through the use of implanted microelectronics in unilateral peripheral facial paralysis could restore eyelid closure following orbicularis oculi muscle denervation.

Biological and artificial nerve conduit for repairing peripheral nerve defect

OBJECTIVE： Recently, with the development of biological and artificial materials, the experimental and clinical studies on application of this new material-type nerve conduit for treatment of peripheral nerve defect have become the hotspot topics for professorial physicians. DATA SOURCES ： Using the terms ＂nerve conduits, peripheral nerve, nerve regeneration and nerve transplantation＂ in English, we searched Pubmed database, which was published during January 2000 to June 2006, for the literatures related to repairing peripheral nerve defect with various materials. At the same time, we also searched Chinese Technical Scientific Periodical Database at the same time period by inputting ＂ peripheral nerve defect, nerve repair, nerve regeneration and nerve graft＂ in Chinese. STUDY SELECTION ： The materials were firstly selected, and literatures about study on various materials for repairing peripheral nerve defect and their full texts were also searched. Inclusive criteria： nerve conduits related animal experiments and clinical studies. Exclusive criteria： review or repetitive studies. DATA EXTRACTION： Seventy-nine relevant literatures were collected and 30 of them met inclusive criteria and were cited. DATA SYNTHESIS ： Peripheral nerve defect, a commonly seen problem in clinic, is difficult to be solved. Autogenous nerve grafting is still the gold standard for repairing peripheral nerve defect, but because of its application limitation and possible complications, people studied nerve conduits to repair nerve defect. Nerve conduits consist of biological and artificial materials. CONCLUSION： There have been numerous reports about animal experimental and clinical studies of various nerve conduits, but nerve conduit, which is more ideal than autogenous nerve grafting, needs further clinical observation and investigation.

Fascial pedicle artificial nerve tissue compared with silicone tube bridging to repair sciatic nerve defects in rats

BACKGROUND： Silicone tube bridging for peripheral nerve defects has been shown to be successful in guiding neural regeneration. However, this method is accompanied by complications. Because materials for bridging nerve fibers should exhibit biocompatibility, the development of novel artificial tissues to bridge nerve grafts has become important in the field of nerve tissue engineering for the repair of peripheral nerve defects. OBJECTIVE： To investigate effectiveness and feasibility of fascial pedicle artificial nerve tissue to repair peripheral nerve defects, and to compare to autologous nerve grafts and silicone tube bridging methods. DESIGN, TIME AND SETTING： Randomized, controlled, neural tissue engineering-based, animal experiments were performed at the Laboratory of Human Anatomy in Qingdao University Medical College from March 2006 to March 2007. MATERIALS： Medical absorbable collagen sponge was purchased from Henan Province Tiangong BJo-Material, China. Cantata 2-track 4-trace EMG-evoked potential instrument was purchased from Dantec, Denmark. Medical silicone tube was purchased from Shenzhen Legend Technology, China. METHODS： Forty healthy, adult, male, Sprague Dawley rats were randomly assigned to four groups fascial pedicle nerve, autologous nerve, silicone tube, and normal, with 10 rats in each group. A 10-mm defective sciatic nerve section was produced in rats following the removal of the fascial pedicle. The fascial flap surrounding the defect was harvested; one side of the nerve pedicle was maintained and then sutured into a tube with the fascia surface as the pipe inner wail. The tube was filled with a medical absorbable collagen （Bodyin） to construct a bridge between the artificial tissue nerve graft and the damaged sciatic nerve. The sciatic nerve defects in the autologous nerve and silicone tube groups were bridged using autologous nerve grafts and a medical silicone tube with matched specifications. MAIN OUTCOME MEASURES： At 4 months after transplantation, electromyogram was used to detect sciatic nerve conduction velocity and action potential amplitude. Hematoxylin-eosin and Nissl staining were used to determine the number of spinal cord anterior horn motor neurons and neurites Osmium tetroxide staining of the sciatic nerve bridge section was performed to detect the number and diameter of nerve fibers. RESULTS： There were no differences in sciatic nerve conduction velocity, action potential amplitude, the number of spinal cord anterior horn motor neurons and neurites, sciatic nerve fiber number, and diameter between the autologous nerve graft and normal groups （P 〉 0.05）. However, these values were significantly greater than in the silicone tube group （P 〈 0.05）. CONCLUSION： Quantitative results suggested that artificial nerve tissue, with an autologous tissue fascia flap as a nerve conduit, could be used to repair peripheral nerve defects. The regenerated fascial pedicle artificial nerve tissue was similar to an autologous nerve graft in terms of morphology and functional recovery and was superior to results from silicone tube bridging transplants.

Repair of sciatic nerve defects using tissue engineered nerves

In this study, we constructed tissue-engineered nerves with acellular nerve allografts in Sprague-Dawley rats, which were prepared using chemical detergents-enzymatic digestion and mechanical methods, in combination with bone marrow mesenchymal stem cells of Wistar rats cultured in vitro, to repair 15 mm sciatic bone defects in Wistar rats. At postoperative 12 weeks, electrophysiological detection results showed that the conduction velocity of regenerated nerve after repair with tissue-engineered nerves was similar to that after autologous nerve grafting, and was higher than that after repair with acellular nerve allografts. Immunohistochemical staining revealed that motor endplates with acetylcholinesterase-positive nerve fibers were orderly arranged in the middle and superior parts of the gastrocnemius muscle; regenerated nerve tracts and sprouted branches were connected with motor endplates, as shown by acetylcholinesterase histochemistry combined with silver staining. The wet weight ratio of the tibialis anterior muscle at the affected contralateral hind limb was similar to the sciatic nerve after repair with autologous nerve grafts, and higher than that after repair with acellular nerve allografts. The hind limb motor function at the affected side was significantly improved, indicating that acellular nerve allografts combined with bone marrow mesenchymal stem cell bridging could promote functional recovery of rats with sciatic nerve defects.