State and local broadband deployment experiences demonstrate the importance of planning and flexibility to effectively implement dig once policies. Officials from states and localities we spoke with have adopted various strategies—including establishing formal coordination processes between state DOTs and local utility companies—but none required installation of conduit as part of all roadway construction. These officials stated that planning and coordination with local officials is a critical step to address a number of considerations that should be taken into account during implementation—such as the location of access points and the appropriate number and size of conduits—to make the conduit installed more useful for telecommunications companies. In addition, officials from states and telecommunication companies stated that the flexibility to take local needs into account in implementing a dig once policy on a project-by-project basis is important and may help to address the potential disadvantages of a federal dig once policy.
Nerve conduits provide a promising strategy for peripheral nerve injury repair. However, the efficiency of nerve conduits to enhance nerve regeneration and functional recovery is often inferior to that of autografts. Nerve conduits require additional factors such as cell adhesion molecules and neurotrophic factors to provide a more conducive microenvironment for nerve regeneration.
Conduits - Conduits (2012)
In the present study, poly(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)] (PLGL) was modified by grafting Gly-Arg-Gly-Asp-Gly (RGD peptide) and nerve growth factor (NGF) for fabricating new PLGL-RGD-NGF nerve conduits to promote nerve regeneration and functional recovery. PLGL-RGD-NGF nerve conduits were tested in the rat sciatic nerve transection model. Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits. All of the 32 Wistar rats were randomly divided into 4 groups: group PLGL-RGD-NGF, group PLGL-RGD, group PLGL and group autograft. At 3 months after surgery, the regenerated rat sciatic nerve was evaluated by footprint analysis, electrophysiology, and histologic assessment. Experimental data were processed using the statistical software SPSS 10.0.
PLGL-RGD-NGF nerve conduits are more effective in regenerating nerves than both PLGL-RGD nerve conduits and PLGL nerve conduits. The effect is as good as that of an autograft. This work established the platform for further development of the use of PLGL-RGD-NGF nerve conduits for clinical nerve repair.
Since the carboxyl groups of PLGL-RGD molecules can also react with the amine groups of NGF molecules in the presence of carbodiimide, we combined PLGL-RGD with NGF to construct a double-functional PLGL-RGD-NGF nerve conduits. The purpose of this study was to investigate the efficiency of PLGL-RGD-NGF nerve conduits to enhance nerve regeneration and functional recovery through the rat sciatic nerve transection model.
Thirty-two male Wistar rats were randomized into 4 groups, 8 weeks old at the beginning of the experiments, 8 rats each: group PLGL-RGD-NGF, group PLGL-RGD, group PLGL and group autograft. The rats were anesthetized with 40mg/kg pentobarbital sodium. The right sciatic nerve was exposed after skin incision, and separation of muscles around the nerve tissues using blunt dissection. Subsequently, the right sciatic nerve was severed into proximal and distal segments in the middle of the right thigh. Defects of 10 mm in the sciatic nerve were created by surgical removal of the nerve tissue. Both the proximal and the distal stumps were secured with 9-0 nylon to a depth of 2 mm into the conduits, leaving a 10 mm gap between the stumps in groups PLGL-RGD-NGF, PLGL-RGD and PLGL. In group autograft, the nerve defect was bridged with the resected nerve segment, which was reversed and anastomosed to the proximal and distal nerve stumps. The wound was closed in two layers with 6-0 nylon sutures.
Transection is one of the most severe injuries in the peripheral nerve. Although peripheral nerves have the potential for regenerating after injury, this capacity is strictly depending on the microenvironment for regeneration. At present there are a few synthetic nerve conduits approved by FDA and CE for clinical nerve repair. These are rudimental conduits that act as a guide for the regenerating axons and as a barrier against the ingrowth of scar-forming tissue. However physical nerve guidance by them may not be sufficient to foster optimal nerve regeneration and functional recovery. NGF is also required in the treatment of peripheral nerve injury to ensure the survival of the cell bodies and to support the regeneration of the axons toward specific target organs. However NGF supplementation alone is insufficient for substantive axonal regrowth. At the same time, cell adhesion molecules such as RGD peptide also play an indispensable role in supporting axonal regrowth. Therefore, we modified PLGL with RGD peptide and NGF to fabricate new PLGL-RGD-NGF nerve conduits.
In S-100 immunocytochemical analysis, we could observed stronger S-100 positive expression in group PLGL-RGD-NGF than that of groups PLGL-RGD and PLGL. Histological assessment showed that the density of myelinated fibers, the mean diameter of axon and the average thickness of myelin sheath in group PLGL-RGD-NGF were similar to those of group autograft, but significantly higher than those of groups PLGL-RGD and PLGL. These showed that PLGL-RGD-NGF nerve conduits could effectively enhance Schwann cells adhesion and migration, axonal growth and the maturity of regenerated myelin sheaths.
New PLGL-RGD-NGF nerve conduits were fabricated by grafting RGD peptides and NGF on PLGL to promote nerve regeneration and functional recovery. The results of cell culture showed that PLGL-RGD-NGF more efficiently enhanced Schwann cells adherence and growth than PLGL. For a 10mm defect in the rat sciatic nerve, nerve regeneration and functional recovery of PLGL-RGD-NGF nerve conduits performed similar to autograft and better than PLGL nerve conduits. This work established the platform for further development of the use of PLGL-RGD-NGF nerve conduits for clinical nerve repair.
Mr. Anant Kshirsagar, an engineer in Pune helped in manufacturing the conduits; and Dr V.K Mahadik, Medical director, R.D Gardi Medical College, Ujjain permitted us to use in the patients
Citation: Lou E, Fujisawa S, Morozov A, Barlas A, Romin Y, Dogan Y, et al. (2012) Tunneling Nanotubes Provide a Unique Conduit for Intercellular Transfer of Cellular Contents in Human Malignant Pleural Mesothelioma. PLoS ONE 7(3): e33093.
Every year, between 250,000 and 500,000 people become spinal cord injured worldwide. Since no effective therapeutic plan, injuries result in life-long disability and a broad range of secondary complications. The spinal cord as a part of the central nervous system (CNS) has a limited regeneration capacity compared with that of the peripheral nervous system. CNS axons do not regenerate appreciably in their native environment because of an impermeable glial scar formation and blocked synaptic target. The current therapeutic approach to SCI patients mainly aims at eliminating further damage to the spinal cord. Much of the research effort in this area has focused on nerve guidance conduits to enhance regeneration across nerve gaps. Nerve guidance conduits are predominantly fabricated as hollow tubes or as porous foam rods because of the ease in the manufacturing of these devices. Recently, multi-channeled conduit is very promising because of its guidance capacity and mimicking natural tissue. A combination of multi-channel structure with nanofibrous matrix was also shown that the physical structure of the basement membrane of the neural matrix and nanofibrous structure of the nerve conduit has facilitated the differentiation of NSCs into neurons. However, very attractive innovative technologies were adapted in the nerve guidance conduits production, significant improvements are still required for the advancement of therapeutic strategy to clinical practice.
Miller, M.S. et al, Pockets, conduits, channels, and plumes: structures within and beneath the continental lithosphere of the western Mediterranean, AGU-CGU Joint Assembly, Montreal, Canada, May 2015. 2ff7e9595c
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