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Image by Hal Gatewood

Article by Eloy Sanchez & Roberta Lock

Tissue-engineered Graft for Nerve Cell Regeneration

Nerve injuries can result in loss of function or sensation that can greatly impact quality of life, and restoring function after a nerve injury is an extremely slow and difficult process. In this work, a tissue-engineered graft was designed to allow young nerve cells to regenerate and bridge the gap between severed nerve segments and accelerate nerve regeneration to prevent degradation of the affected nerves & muscles that may occur during this process.

What did these researchers do?

In this study, researchers created an advanced tissue-engineered graft to aid in the regeneration of axons. These grafts serve to connect missing nerve segments and maintain their regenerative ability by providing a scaffold for the nerves to grow along. After biofabrication of the grafts, rat and pig models with peripheral nerve injury were used to test the graft’s ability to (1) ‘bridge’ the gap in the injured nerve to enhance healing, and (2) ‘babysit’ the surrounding cells to maintain them and keep them in a state that supports healing of the nerve, which are the two processes necessary for nerve regeneration.


Why is this important?

In the United States alone, 20 million people suffer from injuries that damage the nerves outside the spinal cord. These injuries usually result in loss of function or sensation in a person’s limbs, and most treatments are unable to restore function even after surgical intervention. Repair options are limited, and the current gold standard is to use a sensory nerve autograft, which requires harvesting healthy donor nerve from the patient, creating an additional wound site. Other treatments such as nerve transfers also require donor nerves, which are limited in supply. A tissue engineered solution has the potential not only to improve nerve regeneration capacity for improved patient outcomes, but also to eliminate the need to sacrifice healthy donor nerves from other sources.

How did the researchers do this?

Creation of the graft begins with healthy porcine donor neurons that are elongated using a “stretch growth” process. Once grown to the desired length, the elongated cells are placed in a 3D supplemental matrix before being bundled together and inserted within commercially available nerve guidance tubes. The assembly was then surgically implanted in vivo in the gap between a severed nerve in porcine and rodent models. Comparing the axon regeneration results from the engineered graft to that of an autograft (gold standard) and negative control (neural guidance tube without the tissue engineered graft), the team found that their design resulted in the fastest axon regeneration rate. This was marked by special types of support cells called Schwann cells being present throughout the length of the axon as their absence has resulted in denervation in past studies. The team highlighted that the presence and movement of these support cells along the engineered tissue was a characteristic also seen in successful autograft outcomes. Additionally, it was noted that nine months after the graft was inserted, the nerve structure appeared identical to the adjacent undamaged nerve. After ten to eleven months, the compound nerve actional potentials and compound muscle action potentials were comparable to those observed in the autograft. This information implied that the host nerve was able to regrow given the intervention.


Immunofluorescence of sprouting neurons


What comes next?

Although an incredible feat of tissue engineering, this design has only been tested in pigs. Much more testing and time is needed before seeing this application in human patients. This is because even with human stem cells being a potential option for engineered tissues, they require long derivation protocols and preparation periods for elongating the tissues that could lead to delays in surgical repair. Optimization of this workflow will be essential to the adoption of this therapeutic strategy. Additionally, the neurons used to build the scaffold must be harvested from donors, which have limited accessibility, meaning that future iterations of this design may instead work towards using neurons grown from laboratory cell stocks. In practical application, the team envisioned secondary grafts implanted distal to the repair site to further preserve the regenerative capability at the far end of the axon.

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