Peripheral Nerve Regeneration Using Polymeric Nerve Guidance Conduit

 

       Fluorescent microscope image of 
       tyrosine- derived polycarbonate
       nerve conduit

 
     Graduate student Mindy Ezra, MS
      using microscopy to study 
      neuronal cellular behavior on
      various polymeric substrates
      Following peripheral nerve injury, neurons can regenerate; however, there is poor functional recovery due to their limited ability to transverse long gaps and reconnect with their distal targets. Therefore, there is a need to guide regeneration in order to increase functional recovery following injury. In the past decade, tubulization has become a popular method to repair severed nerves as it allows factors and cells to remain in direct contact with the nerve, provides direction, and protects the wound space. A hollow tube or conduit  can be used to bridge together small nerve gaps, <10 mm, but a more complicated internal architecture is necessary to help guide peripheral nerve regeneration for larger nerve gaps.

     To successfully foster nerve regeneration in critically large gaps,the Kohn Lab fabricates a biodegradable, polymeric scaffold using tyrosine-derived polycarbonates that provides physical and biologic guidance (by means of a peptide mimic) to regenerating nerves, directing the nerve on where to navigate. These scaffolds are assessed for their ability to accelerate regeneration of the femoral nerve in mice. Following implantation, scientists perform functional analysis in order to evaluate muscle function during the walking cycle. Moreover, individual axons are also identified in order to determine whether or not the nerves reconnected properly. From these performance outcomes, the polymer composition used for this application can be further optimized and the design of the scaffold improved to enhance regeneration.


 
Figure a.
Scanning electron micrograph of cross-section of porous conduite
Figure b. Mouse femoral nerve injury model used to evaluate nerve conduit's performance
                    Image shows division of the femoral nerve into two separate branches, a motor branch
                    and a sensory
branch
Figure c. Placement of conduit in the mouse model. Inlay shows actual conduit dimensions

Project Leader: Mindy Ezra, MS
Funding Source: CeMBR / Center for Military Biomaterials Research, (DoD grant
W81XWH-04-2-0003)