Building a bridge towards guided neuronal regeneration in spinal cord repair

 

  • Clinical Motivation: Spinal Cord Injury
  • Approach
  • Design
  • Developments
  • References

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Developments: Bridge developments

1. Multiple channel bridges

A number of multiple channel bridges have been developed that have maintained their architecture in vivo, shown significant cellular infiltration, and favorable outside conditions such as growth in astrocyte regions, and limited functional recovery. The following multiple channel bridge shown below was a poly(lactide-co-glycolide) bridge with multiple channels fabricated via a gas foaming / leaching process. The results of this study [28] found correlation between levels of axonal growth and particle diameter and number of channels, and are shown below.

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Bridge implantation into a rat spinal cord lateral hemisection injury model. (a–c) Hematoxylin eosin staining of bridges retrieved at 2 weeks of implantation: (a) Low-magnification image of a bridge implanted in the spinal cord hemisection model. The line marks the border between the bridge and tissue. (b) High-magnification image of cells within the bridge pore structure created by porogen, compared with the alignment of cells in channel of bridge (c). The line defines the edge of a channel with the arrow pointing in the direction of the channel, scale bar = 50 μm. (d,e) Neurofilament stain (NF200) for neurite growth at 12 weeks: (d) inside the channel, scale bar = 100 μm; (e) across the channels of the polymer bridge.

 

 

Significant cellular developments and markers were found post implantation.

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The successful astrocyte distribution in the bridge is also indicative of the success of the bridge in the less permissive astrocyte environment in the distal stump.

 

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2. Microelectronic Channel Bridge

An implantable microelectronic system was recently developed to introduce neural functional recovery in a developed bridge design. The proximal and distal stumps (upper and lower neuron portions respectively) were attached to microelectronic arrays (a detecting and functional electrical stimulation(FES) ), and these arrays were integrated with a microelectronic module. The developed block diagram and results are shown as follows. [29]

 

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In the following rat model, an FES signal was generated from the pulse generator and applied to the interface along the proximal stump (A1). The resulting detected neural spikes (A2) were interfaced to generate another FES signal (B1) along the distal stump. Again resulting neural spikes were detected (B2).

 

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3. Future

The results of this study showcase the success of electrical stimulation in generating instances of functional recovery. Such therapies will prove conclusive in the design of a successful bridge design. Unfortunately today, we are still far from a successful design that incorporates the biological, engineering, and technological approaches that must be successfully integrated to develop the optimal and working bridge. However, the recent advances in the biological knowledge of SCI and axonal regeneration in the CNS, the developments in biomaterials and biodegradable polymers that can be used in such tissue engineering applications, as well as the introduction of microelectronics and the ability to use such FES systems at the small scale will all prove beneficial in developing the successful bridge that may one day be the product for spinal cord injury repair.