Experimental Strategies to Bridge Large Tissue Gaps in the Injured Spinal Cord after Acute and Chronic Lesion

Journal of Visualized Experiments, 2016 · DOI: doi:10.3791/53331 · Published: April 5, 2016

Simple Explanation

After a spinal cord injury, scar tissue forms which prevents nerve fibers from regenerating. This study presents two strategies to bridge the injury site: (1) implanting a microconnector device to reconnect severed spinal cord tissue after acute injury, and (2) filling the injury site with polyethylene glycol (PEG) after scar removal in chronically injured rats. The microconnector system uses negative pressure to pull the spinal cord stumps into a honeycomb structure, promoting tissue adhesion. For chronic injuries, the scar tissue is removed, and the resulting gap is filled with PEG, which supports cellular invasion and nerve fiber regeneration. Both methods have shown promising results in rodent models, promoting nerve fiber regrowth, beneficial cell invasion, and improved function. These strategies aim to facilitate tissue repair and nerve regeneration after spinal cord injuries.

Study Duration

Not specified

Participants

Female Wistar Rats (220 - 250 g)

Evidence Level

Not specified

Key Findings

1
The microconnector system (mMS) stabilized the completely transected spinal cord stumps and decreased shrinkage of the tissue.
2
In chronic injury models, scar resection and subsequent insertion of PEG 600 led to regeneration of tissue which was detectable within the matrix.
3
PEG matrix promoted the substantial regenerative growth of numerous axons, with various ascending and descending axonal populations regenerating into and beyond the PEG-filled area.

Research Summary

The study presents two surgical approaches to bridge tissue gaps in the spinal cord: (1) acute complete transection and mMS implantation, and (2) chronic spinal cord lesion, fibrous scar removal, and PEG matrix implantation. Both strategies aim to promote tissue preservation and axonal regeneration. The mMS uses an internal microchannel system that allows the local infusion of therapeutically active liquids into the lesion core. Future versions of the mMS will be bioresorbable and coated with an electronic conductor material. The low molecular weight PEG 600 is a highly suitable biopolymer to fill the gap resulting from scar removal in chronic injuries. It allows the formation of a stable tissue bridge, promotes angiogenesis, and facilitates the invasion of beneficial cell types.

Practical Implications

mMS Therapeutic Potential

The mMS holds therapeutic potential due to its internal microchannel system which allows local infusion of therapeutic liquids. Future clinical applications may use bioresorbable materials and electronic conductor coatings.

PEG as a Bridging Material

PEG 600 can be used to bridge tissue defects in chronic spinal cord injuries by promoting angiogenesis and cellular invasion of beneficial cell types. The physical properties of PEG600, like viscosity, play important roles in its effectiveness.

Combinatorial Approaches

Future optimization of PEG treatment after chronic spinal cord injury may involve combinatorial approaches, such as seeding the PEG with growth-promoting stem cells like umbilical cord blood cells in vivo.

Study Limitations

1
Adequate fixation of the mMS within the spinal cord is critical.
2
The longer time periods of non-use of the hind limbs result in higher degrees of degenerative events and, therefore, in less prominent functional improvements.
3
mMS not suitable for bridging large tissue gaps of several millimeters.

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