A synthetic oxygen carrier-olfactory ensheathing cell composition system for the promotion of sciatic nerve regeneration.

The treatment of lengthy peripheral nerve defects is challenging in the field of the regenerative medicine. Thus far, many nerve scaffolds with seeded cells have been developed, which hold great potential to replace nerve autograft in bridging lengthy nerve defects by providing guiding and bioactive cues. However, low oxygen status has been found within nerve scaffolds after their implantation in vivo, which has been shown to result in death or loss of function of supportive cells, and significantly limit nerve regeneration and functional recovery after nerve injury. In the present study, perfluorotributylamine (PFTBA) was introduced into a collagen-chitosan conduit within which olfactory ensheathing cells (OECs) were seeded to increase oxygen supply to OECs, as well as regenerating axons. The "PFTBA-OECs" enriched scaffolds were then used to bridge a 15-mm-long sciatic nerve defect in rats. Both nerve regeneration and functional recovery were examined at pre-defined time points after surgery. We found that the number of GFP-labeled OECs was significantly higher in the "PFTBA-OECs" scaffold than that in the single OECs scaffold. In addition, PFTBA was found to enhance the beneficial effect of OECs-enriched scaffold on axonal regeneration and functional recovery. All these findings indicate that the "PFTBA-OECs" enriched scaffolds are capable of promoting nerve regeneration and functional recovery, which might be attributable, at least in part, to their beneficial effect on the survival of OECs after their implantation in vivo.

Zhu S ，Ge J ，Wang Y ，Qi F ，Ma T ，Wang M ，Yang Y ，Liu Z ，Huang J ，Luo Z ... -  《-》

A synthetic oxygen carrier in fibrin matrices promotes sciatic nerve regeneration in rats.

Tissue-engineering nerve conduits have been studied for a long time in bridging large nerve defects. However, the low oxygen availability within the nerve conduits, which results in death of migratory Schwann cells (SC) or loss of the newly formed tissue's function, is still an obstacle for axonal regeneration. Thus, it was hypothesized that an oxygen-enriched conduit would enhance axonal regeneration and functional recovery in vivo. To address this issue, perfluorotributylamine (PFTBA) enriched fibrin hydrogel was prepared and injected into collagen-chitosan conduits. The conduit containing PFTBA-enriched fibrin hydrogel was then used to bridge a 12-mm sciatic nerve defect in rats. The control rats were bridged with collagen-chitosan conduits filled with fibrin matrices without PFTBA. It was found that axonal regeneration and functional recovery in the combined PFTBA group were significantly higher than those in the control group without PFTBA. Further investigations showed that the mRNA and protein levels of S-100, brain-derived neurotrophic factor and nerve growth factor were enhanced by PFTBA at 1 and 3weeks after surgery. However, the mRNA and protein levels of vascular endothelial growth factor were in a similar range between the combined PFTBA group and the control group without PFTBA. In addition, immunohistochemical results showed that the morphological appearances of regenerated nerve and survival of SC were enhanced by PFTBA at 4 and 12weeks after surgery. In conclusion, PFTBA-enriched nerve conduit is capable of enhancing axonal regeneration, which provides a new avenue for achieving better functional recovery in the treatment of nerve defect.

Wang Y ，Qi F ，Zhu S ，Ye Z ，Ma T ，Hu X ，Huang J ，Luo Z ... -  《-》

Enhanced in vivo survival of Schwann cells by a synthetic oxygen carrier promotes sciatic nerve regeneration and functional recovery.

Local hypoxia in the early stages of peripheral nerve injury is a challenge for axonal regeneration. To address this issue, perfluorotributylamine (PFTBA)-based oxygen carrying fibrin hydrogel was prepared and injected into Schwann cell (SC)-seeded collagen-chitosan conduits to increase oxygen supply to SCs within the conduits. The conduit containing PFTBA-SC gel was then applied to bridge a 15-mm sciatic nerve defect in rats. It was observed that most of the GFP-labeled SCs initially seeded in the PFTBA hydrogel remained alive for approximately 28 days after their in vivo implantation. The number of SCs was significantly higher in the PFTBA-SC scaffold than that in the SC scaffold without PFTBA. In addition, nerve regeneration and functional recovery were examined after nerve injury repair. We found that the PFTBA-SC scaffold was capable of promoting axonal regeneration and remyelination of the regenerated axons. Further studies showed the PFTBA-SC scaffold was able to accelerate the recovery of motor and sensory function of the regenerating nerves. Electrophysiological analysis showed area under the curve of compound muscle action potential and nerve conduction velocity were also improved, and gastrocnemius muscle atrophy was partially reversed by PFTBA-SC scaffold. Furthermore, microvessel density analysis showed PFTBA-SC composites were beneficial for microvascular growth, which provided sustained oxygen for regenerating nerve in the later stages of nerve regeneration. In conclusion, enhanced survival of SCs by PFTBA is capable of promoting sciatic nerve regeneration and functional recovery, which provides a new avenue for achieving better functional recovery in the treatment of peripheral nerve injuries. Copyright © 2016 John Wiley & Sons, Ltd.

Ma T ，Zhu L ，Yang Y ，Quan X ，Huang L ，Liu Z ，Sun Z ，Zhu S ，Huang J ，Luo Z ... -  《-》

PLGA conduit seeded with olfactory ensheathing cells for bridging sciatic nerve defect of rats.

PLGA is thought to be a promising material for nerve scaffold. OECs have been shown to promote axon outgrowth and myelination following peripheral nerve transection. This study assessed the compatibility between PLGA and OECs in vitro, and evaluated the effect of PLGA conduit filled with OECs and extracellular matrix gel (ECM) (POE group) on 10 mm-defect sciatic nerve of rats. Silicon-OECs-EMC (SOE group), PLGA-ECM (PE group), and silicon-ECM (SE group)-were used as the controls. The survival and distribution of OECs in vivo, neurohistology and neurofunction of the bridged nerve, were quantitatively evaluated from 1 week to 12 weeks after surgery. PLGA possessed complete compatibility with OECs. After implantation, OECs migrated along the axis of the nerve and survived longer in the POE group than in the SOE group. Gross recovery of the animal, like ulcerious and autophagical rate as well as relative diameter recovery rate of the fiber, was more successful in the POE group than in other groups. The number of the fiber in the middle and distal segments of bridged sites and neurons in anterior horn of the spinal cord was increased in both OECs-contained groups, but the diameter and the myeline thickness of the fiber were increased only in the POE group. The nerve conduction velocity and the amplitude of compound muscle active potential were improved much successfully in the PLGA-guided group than in the silicon-guided group, but the best improvement was encountered in the POE group. Sciatic function index was not improved in all groups at 12 weeks after surgery due to the injury model. These results suggested that PLGA filled with OECs is a significant alternative to conventional autograft in repairing peripheral nerve defects, and OECs are potential seed cells for peripheral nerve tissue engineering.

Li BC ，Jiao SS ，Xu C ，You H ，Chen JM ... -  《-》

Transplantation of olfactory ensheathing cells enhances peripheral nerve regeneration after microsurgical nerve repair.

Radtke C ，Aizer AA ，Agulian SK ，Lankford KL ，Vogt PM ，Kocsis JD ... -  《-》