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 overall focus of the Peripheral Nerve Surgical Research Laboratories (PNSRL) is to investigate the pathology, mechanisms, and treatments for traumatic peripheral nerve injuries. The PNSRL is a consortium of investigators including Matthew Wood, who directs the lab, and Susan Mackinnon.
This lab has a common objective of investigating the pathology, mechanisms, and current/prospective surgical treatments forperipheral 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.
Peripheral nerve injuries are common and associated with long-term morbidity and functional disability. Furthermore, nerve injuries, if not repaired, can lead to additional pathologies forming on the injured nerve end including symptomatic neuroma, which have devastating side effects such as chronic pain.
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 evolved translational research projects that encompass a true “bed to bench-side” 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.
- Pan D, Hunter DA, Schellhardt L, Jo S, Santosa K, Larson E, Fuch AG, Snyder-Warwick AK, Mackinnon SE, Wood MD. The accumulation of T cells within ANAs is length-dependent and critical for nerve regeneration. Exp Neurol. 2019 Aug;318:216-231. PMCID: PMC6605105
- Jo S, Pan D, Halevi AE, Roh J, Schellhardt L, Hunter DA, Snyder-Warwick AK, Moore AM#, Mackinnon SE#, Wood MD#. Comparing electrical stimulation and FK506 to enhance treating nerve injuries. Muscle and Nerve. 2019 Nov;60(5):629-636. #Shared senior/corresponding author
- Yan Y, Hunter DA, Schellhardt L, Ee X, Snyder-Warwick AK, Moore AM, Mackinnon SE, Wood MD. Nerve stepping stone has minimal impact in aiding regeneration across long acellular nerve allografts. Muscle Nerve. 2018 Feb;57(2):260-267. PMCID: PMC5862034
- Hoben G, Ee X, Schellhardt L, Hunter DA, Yan Y, Moore AM, Snyder-Warwick AK, Stewart SA, Mackinnon SE, Wood MD. Increasing nerve autograft length increases senescence and reduces regeneration. Plast Reconstr Surg. 2018 Oct;142(4):952-961. PMCID: PMC6156921
- Wang ZZ, Wood MD, Mackinnon SE, Sakiyama-Elbert SE. A Microfluidic Platform to Study the Effects of GDNF on Neuronal Axon Entrapment. J Neurosci Methods. 2018 Oct 1;308:183-191. PMCID: PMC6200633
- Poppler LH, Schellhardt L, Hunter DA, Yan Y, Mackinnon SE, Wood MD, Moore AM. Selective Nerve Root Transection in the Rat Produces Permanent, Partial Nerve Injury Models with Variable Levels of Functional Deficit. Plast Reconstr Surg. 2017 Jan;139(1):94-103.
- Agenor A*, Dvoracek L*, Leu A, Hunter DA, Newton P, Yan Y, Johnson PJ, Mackinnon SE, Moore AM, Wood MD. Hyaluronic acid/carboxymethyl cellulose directly applied to transected nerve decreases axonal outgrowth. J Biomed Mater Res B Appl Biomater. 2017 Apr;105(3):568-574. *Shared first author
- Ee X, Yan Y, Hunter DA, Schellhardt L, Sakiyama-Elbert SE, Mackinnon SE, Wood MD. Transgenic SCs expressing GDNF-IRES-DsRed impair nerve regeneration within acellular nerve allografts. Biotechnol Bioeng. 2017 Sep;114(9):2121-2130. PMCID: PMC5526100
- Yan Y, Wood MD, Hunter DA, Ee X, Mackinnon SE, Moore AM. The Effect of Short Nerve Grafts in Series on Axonal Regeneration Across Isografts or Acellular Nerve Allografts. J Hand Surg Am. 2016 Jun;41(6):e113-21.
- Poppler LH, Ee X, Schellhardt L, Hoben G, Pan D, Hunter DA, Yan Y, Moore AM, Snyder-Warwick AK, Stewart SA, Mackinnon SE, Wood MD. Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts. Tissue Eng Part A. 2016. Jul;22(13-14):949-61. PMCID: PMC4948214
- Farber SJ, Hoben GM, Hunter DA, Yan Y, Johnson PJ, Mackinnon SE, Wood MD. Vascularization is delayed in long nerve grafts. Muscle Nerve. 2016 Aug;54(2):319-21. PMCID: PMC4940276
- Zhou H, Yan Y, Du T, Ee X, Hunter DA, Akers WA#, Wood MD#, Berezin M#. Imaging of radicals following injury or acute stress in peripheral nerves with activatable fluorescent probes. Free Radic Biol Med. 2016 Dec;101:85-92. PMCID: PMC5154790 #Shared senior/corresponding author
- Yan Y, Wood MD, Moore AM, Snyder-Warwick AK, Hunter DA, Newton P, Poppler LH, Tung TH, Johnson PJ, Mackinnon SE. Robust axonal regeneration in a mouse vascularized composite allotransplant model undergoing delayed tissue rejection. HAND. 2016. Nov;11(4) 456–463.
- Hoben G, Moore AM, Yan Y, Iyer N, Newton P, Hunter DA, Sakiyama-Elbert SE, Wood MD, Mackinnon SE. Comparison of acellular nerve allograft modification with Schwann cells or VEGF. Hand (N Y). 2015 Sep;10(3):396-402. PMCID: PMC4551644
- Roam JL, Yan Y, Nguyen PK, Kinstlinger IS, Leuchter MK, Hunter DA, Wood MD, Elbert DL. A Modular, Plasmin-Sensitive, Clickable Poly(ethylene glycol)-Heparin-Laminin Microsphere System for Establishing Growth Factor Gradients in Nerve Guidance Conduits. Biomaterials. 2015 Dec;72:112-24. PMCID: PMC4591245
- Marquardt LM, Ee X, Iyer N, Hunter DA, Mackinnon SE, Wood MD, Sakiyama-Elbert SE. Finely Tuned Temporal and Spatial Delivery of GDNF Promotes Enhanced Nerve Regeneration in a Long Nerve Defect Model. Tissue Eng Part A. 2015 Dec;21(23-24):2852-64. PMCID: PMC4684669
- Wood MD and Mackinnon SE. Pathways regulating modality-specific axonal regeneration in peripheral nerve. Commentary. Exp Neurol. 2015. Mar;265:171-5. PMCID: PMC4399493
- Wu-Feinberg Y, Moore AM, Marquardt L, Newton P, Johnson PJ, Mackinnon SE, Sakiyama-Elbert SE, Wood MD. Viral transduction of primary Schwann cells using a Cre-lox system to regulate GDNF expression. Biotechnol Bioeng. 2014. Sep; 111(9):1886-94. PMCID: PMC4117799
- Saheb-Al-Azmani M, Yan Y, Farber SJ, Hunter DA, Newton P, Wood MD, Stewart SA, Johnson PJ, Mackinnon SE. Limited regeneration in long acellular nerve allografts is associated with increased Schwann cell senescence. Exp Neurol. 2013. Sep;247:165-77. PMCID: PMC3863361
- Johnson PJ, Wood MD, Moore AM, and Mackinnon SE. Tissue Engineered Constructs for Peripheral Nerve Surgery. Review. European Surgery Acta Chirurgica Austriaca. 2013. June;45(3):122-35. PMCID: PMC3875220
- Jesuraj NJ, Santosa KB, Macewan MR, Moore AM, Kasukurthi R, Ray WZ, Flagg ER, Hunter DA, Borschel GH, Johnson PJ, Mackinnon SE, Sakiyama-Elbert SE. Schwann cells seeded in acellular nerve grafts improve functional recovery. Muscle Nerve. 2014 Feb;49(2):267-76. doi: 10.1002/mus.23885. Epub 2013 Nov 22. PMID: 23625513
- Farber SJ, Glaus SW, Moore AM, Hunter DA, Mackinnon SE, Johnson PJ. Supercharge nerve transfer to enhance motor recovery: a laboratory study. J Hand Surg Am. 2013 Mar;38(3):466-77. doi: 10.1016/j.jhsa.2012.12.020. Epub 2013 Feb 5. PMID: 23391355
- Santosa KB, Jesuraj NJ, Viader A, MacEwan M, Newton P, Hunter DA, Mackinnon SE, Johnson PJ. Nerve allografts supplemented with schwann cells overexpressing glial-cell-line-derived neurotrophic factor. Muscle Nerve. 2013 Feb;47(2):213-23. doi: 10.1002/mus.23490. Epub 2012 Nov 21. PMID: 23169341
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 email@example.com about your interest. A follow-up email and/or interview will be scheduled.
We provide research opportunities for graduate students (Masters, PhD, and MD/PhD) to complete their thesis within the Lab. 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 firstname.lastname@example.org 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
Administrative Office Location
The administrative offices of the Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, can be contacted at:
Washington University School of Medicin
Northwest Tower, Suite 1150
660 South Euclid Avenue
St. Louis, MO 63110