April 8, 2019
Tissue engineering and regenerative medicine hold the promise of new treatment approaches to spinal cord injuries. Since the human body doesn’t naturally regenerate tissues of the spinal cord, new materials and structures that have similar characteristics to native tissue are needed to realize the potential.
Structure is one critical tissue characteristic, particularly in the spinal cord, where nerve tissue is arranged in bundles. Trauma to the tissue can disrupt the structure, impacting tissue function and leading to problems with both sensing and mobility.
Currently, few treatments exist for repairing spinal cord injuries, whether those injuries are due to impact or trauma. Complicating matters is the inflammatory response that often accompanies these injuries, further impeding healing, regeneration and recovery of function.
Biomaterials can help balance the microenvironment around an injury, and physical guidance systems can help new tissues to organize properly so they can regain their original function. Guidance systems such as conduits and preformed scaffolds with multiple channels, called bridges, have been used, yet these preformed structures can be difficult to apply to injuries with an irregular shape. Hydrogels have been promising for spinal cord repair since their mechanical properties can mimic those of the native tissue and the gels can fit to the contours of the injury, yet these hydrogels are amorphous and do not provide directional guidance cues.
“We need a platform that can be readily inserted at the injury that provides a permissive environment that supports, promotes, and guides regeneration,” said Lonnie Shea, the Steven A. Goldstein Collegiate Professor of Biomedical Engineering.
Shea, also chair of the BME department, is the principal investigator of work detailed in an article, “Aligned hydrogel tubes guide regeneration following spinal cord injury,” recently published in Acta Biomaterialia. For the first time, he and collaborators have developed and demonstrated a novel, modular hydrogel tube system that addresses the need both to conform to the injury shape and provide directional guidance.
“Aligned hydrogel tubes guide regeneration following spinal cord injury.” Lonnie Shea
The tubes have a high degree of porosity, which supports tissue growth from all sides, and a central channel that can orient and direct axon growth across the injury. They are small in size and scale — the lumen of the tubes is approximately 200 microns in diameter, and the tubes are several millimeters in length. During a procedure, the channels can be cut to the appropriate length and placed one at a time to fit the wound.
“Imagine needing to move a pool table into your house and the table needs to go in through the doorway. If the doorway isn’t wide enough, it’s hard to get in. But if you disassemble the table and insert it piece by piece, you can then assemble it inside without damage the walls or doorway,” said Shea, by way of analogy.
Creating the modular tube system from hydrogel material addresses the second challenge.
“The tubes we’ve made have an orientation,” Shea says. “We’ve taken the gels that have mechanical properties that match the tissues, yet now we’ve given it the ability to guide regenerating nerves after an injury.”
“We’ve taken the gels that have mechanical properties that match the tissues, yet now we’ve given it the ability to guide regenerating nerves after an injury.” Lonnie Shea
In experiments using the modular hydrogel tubes on an animal model of spinal cord injury, the team found that nerves indeed filled the voids of the tubes and that the density of the cells was three times greater than in the control group.
In addition, individuals with the modular tubes had a shorter inflammatory response, less scarring and showed signs of functional recovery as well. Because they are easier to fit to an injury than preformed scaffolds or bridges, the modular hydrogel tubes reduce the risk of further damage at the time of insertion.
The findings are promising, and Shea is looking ahead. “Not only do we need the neurons to grow in, we also need to enable other cell types that support functions of the nerves.”
Shea is referring in part to oligodendrocytes, or myelinating cells that wrap around nerve cells and help with signal conduction. “We need the whole tissue to regenerate if we want to support the restoration of its original function,” he adds.
Currently, the investigators are looking at combining the tubes with gene therapy approaches that express anti-inflammatory factors and neurotrophic factors that drive axons to come in and bring those myelinating cells, too.
If successful, the work may one day lead to new treatment options, and hope, for patients with spinal cord injuries – and for those with injuries to other tissues as well, including of the veins, arteries, bones and muscles.
The work was funded by a National Institutes of Health R01 grant.
Credits & Links:
By: Kim Roth, BME Writer
Paper: Dumont C., et al. Aligned hydrogel tubes guide regeneration following spinal cord injury. Acta Biomater. 2019 Mar 1;86:312-322. doi: 10.1016/j.actbio.2018.12.052. Epub 2019 Jan 2.