The overall focus of the Peripheral Nerve Surgical Research Laboratories (PNSRL) is to investigate the pathology, mechanisms, and treatments for traumatic peripheral nerve injuries. Peripheral nerve injuries are common and associated with long-term morbidity and functional disability.

The PNSRL is a consortium of investigators including Dr. Matthew Wood, who directs the lab, and Dr. Susan Mackinnon. The laboratories utilize animal models of peripheral nerve injury combined with surgical and experimental treatments to test prospective clinical treatments and provide insights into biological processes of nerve regeneration within the context of surgical repair.

The PNSRL uses a multidisciplinary approach to study how to treat nerve injuries, where studies focus on these major areas:

Translational Advances to Treat Peripheral Nerve Injuries

The group has continuously evolving translational research projects that encompass a true “bed to benchside” research approach. As an example of a translational research project, our group has demonstrated the efficacy of a commercially available material to reduce aberrant axon growth, such as axon growth that could lead to painful neuroma formation. Hyaluronic acid/carboxymethyl cellulose (HA/CMC) is an anti-adhesive, biodegradable material that is non-toxic to nerve. Placing this biomaterial around an injured nerve inhibited axon growth. These biomaterials may prove to be a tool to prevent neuroma formation by inhibiting axonal growth.

Rodent nerves are useful models to study nerve regeneration. Immunohistochemistry, as well as light and electron microscopy, assess the quality of nerve regeneration in our experimental surgical models.

Severe Nerve Injuries: Understanding the limits to repairing nerve gaps

Severe peripheral nerve injuries can result in a gap generated within the nerve. This results in loss of critical functions, such as sensation and motor control, as signals from the neurons through these axons cannot be transmitted. In most instances, a “bridge” material is needed to facilitate axon regeneration across the gap.

We are focused on determining why clinically-available, bioengineered alternatives, such as nerve guidance conduits or tissue-engineered acellular nerve allografts, have significant limitations that limit their use. Specifically, as the length and size of these alternatives increases, regeneration and functional recovery decreases substantially. Our studies have revealed that the cells repopulating these alternatives differs as a function of the alternative length and size. Our studies have demonstrated that long alternatives are repopulated with a cellular population imbalance, consisting of increased populations of stromal cells, as well as Schwann cells expressing markers of senescence, compared to short or small alternatives. Furthermore, how the immune response reacts to these alternatives differs based on their length and size. These cumulative changes alter the regenerative environment and represent a “barrier” to axon regeneration across the larger alternatives.

Rodent nerves with endogenous GFP expression are used as models to visualize axon growth across nerve grafts. As shown in this image, autografts promote axon growth across long gaps while alternatives, such as acellular nerve, have limits to their regenerative capabilities.

Severe Nerve Injuries: Developing approaches to repair large gaps

To overcome these issues and to complement these studies, we are developing tissue-engineered approaches to promote regeneration. We are using specific approaches that overcome the deficiencies we have identified within longer and larger scaffolds. For example, we are designing scaffolds that “tune” the immune response within long and large scaffolds to facilitate angiogenesis and regeneration, similar to how these endogenous processes normally facilitate regeneration across shorter versions of alternatives.

In an approach to improve acellular nerve scaffolds, a drug delivery system containing fibrin (green) and cytokines (red) was loaded within the scaffold to modulate the immune response to promote regeneration.