The Peripheral Nerve Surgical Research Laboratories (PNSRL) investigate the pathology, mechanisms, and treatments for peripheral nerve injuries. The PNSRL is a consortium of investigators with a common objective of investigating the pathology, mechanisms, and current/prospective clinical treatments of peripheral nerve injury.
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. The laboratory quantifies regeneration via histology, electrophysiology, in vivo imaging, and functional outcomes. The work from the lab has led directly to changes in the clinical treatment of patients with peripheral nerve injury and to new understanding of nerve regeneration.
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.
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.
We provide research opportunities for medical students coordinated through the office of medical student research. Students are first encouraged to determine their primary interests within the scope of the group’s projects. Throughout the research experience, each student meets regularly with their primary mentor, as well as all investigators during weekly meetings.
More information can be found about this opportunity through the Office of Medical Student Research.
Next step? After discussing with the office of medical student research, send an email with your CV to firstname.lastname@example.org about your interest. A follow-up email and/or interview will be scheduled.
The Peripheral Nerve Surgical Research Group provides research opportunities for graduate students (Masters, PhD, and MD/PhD). These opportunities are coordinated through a variety of different programs offered through Washington University:
- A Masters in Arts via the Division of Biology and Biomedical Science (DBBS)
- A PhD or MD/PhD via DBBS under the Developmental, Regenerative, and Stem Cell Biology or Neurosciences programs
Next step? After admission to one of these programs, send an email with your CV to email@example.com about your interest. A follow-up email and/or interview will be scheduled.
The Peripheral Nerve Surgical Research Laboratories:
Washington University School of Medicine
Clinical Sciences Research Building, Room 3352
4925 Children’s Place
St. Louis, MO 63110
Office Phone: 314-362-1275
Lab Phone: 314-362-8322
The administrative offices of the Division of Plastic and Reconstructive Surgery:
Washington University School of Medicin
Northwest Tower, Suite 1150
660 South Euclid Avenue
St. Louis, MO 63110