The Ray Laboratory is dedicated to improving the lives of patients with nerve and spinal cord injuries. The Lab is actively working to develop a stable peripheral nerve neuroprosthetic platform and identify non-invasive biomarkers predictive of recovery following spinal cord injury.
Nerve regeneration: Sieve electrodes
We are investigating strategies to improve nerve regeneration and are focused on the development of innovative technology targeting peripheral nerve/neuroprosthetic interfaces. The lab takes an interdisciplinary approach to effectively engineer novel technological platforms, medical devices and clinical therapies with significant potential for clinical translation. Lab members contribute diverse experiences and backgrounds in the fields of tissue engineering, device design, biomedical engineering, nanotechnology and neurosurgery.
Loss of motor and sensory function due to spinal cord, brachial plexus and/or peripheral nerve injuries can result in partial or total loss of motor and sensory function. Despite aggressive reconstruction procedures, patients with spinal cord and nerve injuries are often left with permanent neurologic deficit. Using nanotechnology, it is possible to interface nerves with micro-machined electrodes to provide motor stimulation and sensory recording. Our goal is to optimize a stable sieve electrode capable of providing simultaneous motor and sensory information to patients with spinal cord injury or severe nerve injuries.
Spinal cord Injury
Spinal cord injury (SCI) is a significant public health problem with approximately 12,000 new cases each year. Tetraplegia, or injury at the level of the cervical spine, is the most common type of paralysis representing over 60% of new cases of SCIs. Although significant resources have been invested into identifying neuroprotective or neuroregenerative agents that produce reliable improvements in neurologic function after an SCI, there remains a significant void in meaningful therapeutic interventions.
A major shortcoming limiting efforts to improve the treatment of SCI is the lack of quantifiable metrics on which to base clinical decisions. Biomarkers are emerging in many fields as valuable predictors of a patient’s clinical course and response to therapy. Noninvasive techniques such as magnetic resonanceimaging (MRI), and in particular diffusion tensor imaging (DTI), may serve as a useful biomarker for neurologic diseases such as spinal cord injury. One of our long-term goals is to establish and validate noninvasive imaging biomarkers that are predictors of clinical course and therapeutic response after a cervical SCI. Our central hypothesis is that axonal injury produced by acute SCI results in alterations of DTI parameters that are predictive of acute and chronic neurologic function. We hypothesize that brain DTI parameters will change with cortical reorganization and in response to chronic denervation after an SCI. The identification and validation of such noninvasive DTI biomarkers will provide guidance for both clinical management and long-term prognosis. We also expect these findings will serve as a useful tool in counseling families and in patient selection for future SCI clinical trials.
Principal Investigator: Wilson Zachary Ray, MD
MacEwan MR, Wheeler JJ, Kim J, Williams JC, Sakiyama-Elbert SE, Moran DW. “Controlled delivery of nerve growth factor enhances sieve electrode interface with peripheral nerve tissue.” J Neural Eng. [Submitted]
Gamble P, Stephen MS, MacEwan MR, Ray WZ. “Serial assessment of functional recovery following nerve injury utilizing implantable thin-film wireless nerve stimulators.” Muscle Nerve. [Submitted]
MacEwan MR, Zellmer E, Siewe DY, Wheeler JJ, Moran DW. “Selective stimulation of regenerated motor axons via macro-sieve electrodes.” J Neurosci [In Preparation]
MacEwan MR, Talcott M, Moran DM, Leuthardt E. “Novel spinal instrumentation to enhance osteogenesis and fusion: A preliminary study.” J. Neurosurg. Spine. [Submitted]
MacEwan MR, Kovacs T, Talcott M, Ray WZ. “In vivo performance of nanofabicated biosynthetic dural substitute in a rabbit duraplasty model.” J. Neurosurg. [In Preparation]
MacEwan MR, Zellmer E, Wheeler JJ, Moran DW. “Dual layer macro sieve electrodes facilitate unidirectional action potential initiation in regenerated peripheral nerve.” J Neurophys. [In Preparation]
Zellmer E, MacEwan MR, Moran DW. “Subthreshold depolarizing pre-pulses improve selectivity of activation of chronically implanted macro-sieve electrodes.” J Neural Eng. [In Preparation]
Zellmer E, MacEwan MR, Moran DW. “Optimization of functional electrical stimulation of regenerated peripheral nerve tissue.” J Neural Eng. [In Preparation]
MacEwan MR, Watt A, Wyczalkowski M, Moran DW. “Optimizing regenerative electrode design and mechanical stability.” IEEE. [In Preparation]
Zellmer E, MacEwan MR, Moran DW. “Implantable Wireless System for Multi-channel, Electrical Stimulation through High Impedance Neural Interfaces.” J Neural Eng. [In Preparation]
Xie J, MacEwan MR, Liu W, Jesuraj N, Li X, Hunter D, Xia Y. “Nerve guidance conduits based on double-layered scaffolds of electrospun nanofibers for repairing the peripheral nervous system”. ACS Appl Mater Interfaces. 2014 Jun 25;6(12):9472-80.
Xie, Jingwei, et al. “Neurite Outgrowth on Electrospun Nanofibers with Uniaxial Alignment: The Effects of Fiber Density, Surface Coating, and Supporting Substrate.” ACS Nano 8.2 (2014): 1878-1885.
Laughner, Jacob I., Scott B. Marrus, Erik R. Zellmer, Carla J. Weinheimer, Matthew R. MacEwan, Sophia X. Cui, Jeanne M. Nerbonne, and Igor R. Efimov. “A fully implantable pacemaker for the mouse: From battery to wireless power.” PloS one 8, no. 10 (2013): e76291.
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 49.2 (2014): 267-276.
Yan Y, MacEwan MR, Hunter DA, Farber S, Newton P, Tung TH, Mackinnon SE, Johnson PJ. “Nerve Regeneration in Rat Limb Allografts: Evaluation of Acute Rejection Rescue.” Plastic and reconstructive surgery 131.4 (2013): 499e.
Choi SW, Zhang Y, Macewan MR, Xia Y. “Neovascularization in biodegradable inverse opal scaffolds with uniform and precisely controlled pore sizes.” Advanced healthcare materials 2.1 (2013): 145-154.
Santosa KB, Jesuraj NJ, Viader A, MacEwan M, Newton P, Hunter DA, Mackinnon SE, Johnson PJ., et al. “Nerve allografts supplemented with schwann cells overexpressing glial‐cell‐line–derived neurotrophic factor.” Muscle & nerve 47.2 (2013): 213-223.
Cai X, Zhang Y, Li L, Choi SW, MacEwan MR, Yao J, Kim C, Xia Y, Wang LV. “Investigation of neovascularization in three-dimensional porous scaffolds in vivo by a combination of multiscale photoacoustic microscopy and optical coherence tomography.” Tissue Engineering Part C: Methods 19.3 (2012): 196-204.
Ebersole GC, Buettmann EG, MacEwan MR, Tang ME, Frisella MM, Matthews BD, Deeken CR. “Development of novel electrospun absorbable polycaprolactone (PCL) scaffolds for hernia repair applications.” Surgical endoscopy 26.10 (2012): 2717-2728.
Lin KF, Sun HH, Macewan MR, Mackinnon SE, Johnson PJ. “GDNF overexpression fails to provoke muscle recovery from botulinum toxin poisoning: A preliminary study.” Microsurgery 32.5 (2012): 370-376.
Xie J, Michael PL, Zhong S, Ma B, MacEwan MR, Lim CT. “Mussel inspired protein‐mediated surface modification to electrospun fibers and their potential biomedical applications.” Journal of Biomedical Materials Research Part A 100.4 (2012): 929-938.
Long-term culture of HL-1 cardiomyocytes in modular poly(ethlyene glycol) microsphere-based scaffolds cross linked in the phase-separated state. Smith AW, Segar CE, Nguyen PK, MacEwan MR, Efimov IR, Elbert DL. Act Biomater. 2012 Jan; 8(1):31-40. doi:10.1016/j.actbio.2011.08.021. Epub 2011 Aug 30.
Fabrication of Density Gradients of Biodegradable Polymer Microparticles and Their Use in Guiding Neurite Outgrowth. Li X, Macewan MR, Xie J Dr, Siewe D, Yuan X, Xia Y. Adv Funct Mater. 2010 May 25;20(10):1632-1637.
Acellular nerve allografts in peripheral nerve regeneration: a comparative study. Moore AM, MacEwan M, Santosa KB, Chenard KE, Ray WZ, Hunter DA, Mackinnon SE, Johnson PJ. Muscle Nerve. 2011 Aug;44(2):221-34. doi: 10.1002/mus.22033. Epub 2011 Jun 9.
Nanofiber membranes with controllable microwells and structural cues and their use in forming cell microarrays and neuronal networks. Xie J, Liu W, MacEwan MR, Yeh YC, Thomopoulos S, Xia Y. Small. 2011 Feb 7;7(3):293-7. doi: 10.1002/smll.201001446. Epub 2010 Nov 22. No abstract available.
Radially aligned, electrospun nanofibers as dural substitutes for wound closure and tissue regeneration applications. Xie J, Macewan MR, Ray WZ, Liu W, Siewe DY, Xia Y. ACS Nano. 2010 Sep 28;4(9):5027-36. doi: 10.1021/nn101554u.
Electrospun nanofibers for neural tissue engineering. Xie J, MacEwan MR, Schwartz AG, Xia Y. Nanoscale. 2010 Jan;2(1):35-44. doi: 10.1039/b9nr00243j. Epub 2009 Oct 27. Review.
Fibrin matrices with affinity-based delivery systems and neurotrophic factors promote functional nerve regeneration. Wood MD, MacEwan MR, French AR, Moore AM, Hunter DA, Mackinnon SE, Moran DW, Borschel GH, Sakiyama-Elbert SE. Biotechnol Bioeng. 2010 Aug 15;106(6):970-9. doi: 10.1002/bit.22766.
The differential effects of pathway- versus target-derived glial cell line-derived neurotrophic factor on peripheral nerve regeneration. Magill CK, Moore AM, Yan Y, Tong AY, MacEwan MR, Yee A, Hayashi A, Hunter DA, Ray WZ, Johnson PJ, Parsadanian A, Myckatyn TM, Mackinnon SE. J Neurosurg. 2010 Jul;113(1):102-9. doi: 10.3171/2009.10.JNS091092.
Conductive Core-Sheath Nanofibers and Their Potential Application in Neural Tissue Engineering. Xie J, Macewan MR, Willerth SM, Li X, Moran DW, Sakiyama-Elbert SE, Xia Y. Adv Funct Mater. 2009 Jul 24;19(14):2312-2318.
Neurite outgrowth on nanofiber scaffolds with different orders, structures, and surface properties. Xie J, MacEwan MR, Li X, Sakiyama-Elbert SE, Xia Y. ACS Nano. 2009 May 26;3(5):1151-9. doi: 10.1021/nn900070z.
The differentiation of embryonic stem cells seeded on electrospun nanofibers into neural lineages. Xie J, Willerth SM, Li X, Macewan MR, Rader A, Sakiyama-Elbert SE, Xia Y.Biomaterials. 2009 Jan;30(3):354-62. doi: 10.1016/j.biomaterials.2008.09.046. Epub 2008 Oct 17.
Student Research Award in the Undergraduate Degree Candidate category, 30th Annual Meeting of the Society for Biomaterials, Memphis, Tennessee, April 27-30, 2005. Monocyte/lymphocyte interactions and the foreign body response: in vitro effects of biomaterial surface chemistry. MacEwan MR, Brodbeck WG, Matsuda T, Anderson JM. J Biomed Mater Res A. 2005 Sep 1;74(3):285-93.
Lymphocytes and the foreign body response: lymphocyte enhancement of macrophage adhesion and fusion. Brodbeck WG, Macewan M, Colton E, Meyerson H, Anderson JM. J Biomed Mater Res A. 2005 Aug 1;74(2):222-9.
Repeated in vivo electrochemical activation and the biological effects of microelectromechanical systems drug delivery device. Shawgo RS, Voskerician G, Duc HL, Li Y, Lynn A, MacEwan M, Langer R, Anderson JM, Cima MJ. J Biomed Mater Res A. 2004 Dec 15;71(4):559-68.
Effect of soft-segment chemistry on polyurethane biostability during in vitro fatigue loading. Wiggins MJ, MacEwan M, Anderson JM, Hiltner A. J Biomed Mater Res A. 2004 Mar 15;68(4):668-83.