DEGREE (if applicable) University of California, Berkeley BS 05/2001 Bioengineering University of California, Berkeley Haas Business School

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1 NAME: Metzger, Melodie F OMB No /0002 (Rev. 08/12 Approved Through 8/31/2015) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. era COMMONS USER NAME (credential, e.g., agency login): METZGERM1 POSITION TITLE: Research Scientist, Instructor EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) INSTITUTION AND LOCATION DEGREE (if applicable) Completion Date MM/YYYY FIELD OF STUDY University of California, Berkeley BS 05/2001 Bioengineering University of California, Berkeley Haas Business School 05/2008 Management of Technology University of California, San Francisco PhD 09/2009 Bioengineering A. Personal Statement My background and education is in biomechanical engineering. Over the past 10 years my training and knowledge has been dedicated to understanding the mechanical and structural aspects of orthopaedic reconstructive surgeries through in vitro cadaveric studies. In addition to this work, some of my more recent studies have included in vivo models designed to better understand how metabolic disease affects bone formation and healing. Specifically, my lab has investigated the role of vitamin D in bone formation after spinal fusion surgery. We are also currently working on two projects to determine the effect of diabetes on bone growth and healing after fusion surgery. Through these studies I have taken my expertise in biomechanical testing and applied it to small animal models, providing quantitative data on the mechanical properties of bone ex vivo. Given this experience, my lab is well-equipped and qualified to conduct the biomechanical testing outlined in this research proposal. Below are two recent publications detailing methodologies similar to that which will be implemented in the current proposal. 1. S.T. Robinson, M.T. Svet, M.F. Metzger, "Four-Point Bending as a Method for Quantitatively Evaluating Spinal Arthrodesis in a Rat Model", Journal of Comparative Medicine 65(1):46-50 (2015) 2. M.F. Metzger, L.E.A. Kanim, L. Zhao, S.T. Robinson, R.B. Delamarter. "The Relationship between Serum Vitamin D Levels and Spinal Fusion Success: A Quantitative Analysis", Spine 40(8):E (2015). B. Positions and Honors Positions and Employment 2009 Present Research Scientist, Instructor, Department of Surgery, Cedars Sinai Medical Center (CSMC), Los Angeles, CA Doctoral Candidate, Joint Graduate Group in Bioengineering at University of California at San Francisco and Berkeley, Dissertation Title: Evaluation of Spinal Reconstructive Surgeries Using Multi-Body System Dynamics Advisor: Jeffrey C. Lotz, Ph.D President, Sierra Interventions, LLC, Berkeley, CA Engineer, Medical Technology Program, Lawrence Livermore National Lab, Livermore, CA.

2 Research Manager, Sierra Internal Medicine, Incline Village, NV. Other Experience and Professional Memberships Member, Tau Beta Pi, Engineering Honor Society Scientific Reviewer, Research Committee, The International Society for the Advancement of Spine Surgery Member, American Society of Mechanical Engineers Director of the Biomechanics Laboratory, Cedars Sinai Medical Center Member, AOSpine North America Resident Research Committee, Cedars Sinai Medical Center Resident Education Committee, Cedars Sinai Medical Center Editorial Review Board, American Journal of Sports Medicine Editorial Review Board, Journal of Engineering in Medicine Honors Kilpatrick Scholarship, Moulett, L. Scholarship, Hearst, Phoebe Scholarship, and Rodkey Scholarship recipient, University of California, Berkeley 2001 American Society of Laser Medicine and Surgery Travel Grant Recipient 2001 Nomination for UC Berkeley University Medal National Science Foundation Graduate Research Fellowship Recipient 2008 Earl C. Anthony Travel Award, UCSF 2009 Graduate Student Association Travel Award, UCSF 2012 Clinical and Translational Science Institute (CTSI) research core award, UCLA/CSMC 2015 Clinical and Translational Science Institute (CTSI) research core award, UCLA/CSMC C. Contributions to Science 1. While at Lawrence Livermore National Laboratories and Sierra Interventions I contributed to several projects that focused on the development and design of a number of interventional devices based on shape memory polymer (SMP). SMP is a smart material that has the ability to remain in a secondary geometry and then actuate to a primary geometry when introduced to a stimulus such as heat. Some of the initial work invested into these devices was based on two NIH SBIR grants (R43 NS / R43 EB /) of which I was the principal investigator. These devices have since followed Dr. Maitland and his Biomedical Device Laboratory to Texas A&M University ( where they are currently being developed for clinical use. a. Metzger, M.F., D. Schumann, T.S. Wilson, D.L. Matthews, and D.J. Maitland, Mechanical Properties of a Mechanical Actuator for Treating Ischemic Stroke, Journal of Biomedical Microdevices 4(2):89-96 (2002) b. Maitland, D.J., Metzger M.F., D. Schumann, T.S. Wilson, A. Lee, and D.L. Matthews, Photothermal Properties of Laser-Activated Shape Memory Polymer Microactuators for Treating Stroke, Lasers in Surgery and Medicine 30:1-11(2002) c. Small, W., IV, Metzger, M.F., Wilson, T.S., Maitland, D.J., Laser-activated shape memory polymer microactuator for thrombus removal following ischemic stroke: preliminary in vitro analysis IEEE Journal of Selected Topics in Quantum Electronics 11(4): (2005) 2. My graduate studies led me to the field of orthopaedic biomechanics and the dynamic modeling of joint reconstruction, primarily of the human spine. My contributions to science in this area of research has been to help develop multi-scale models of the human spine which have been used to show the effects of total disc replacement on the mechanics of a vertebral joint and the stability of the spine in the sagittal plane. a. O'Reilly, O.M, Metzger M.F., Buckley J.P., Moody D.A., Lotz J.C., On the Stiffness Matrix of the Intervertebral Joint: Application to Total Disc Replacement ASME Journal of Biomechanical Engineering, 131(8):63-87 (2009)

3 b. Metzger M.F., Faruk Senan N.A., O Reilly O.M., "On Cartesian Stiffness Matrices in Rigid Body Dynamics: An Energetic Perspective", Journal of Multibody System Dynamics, 24(4): (2010) c. Metzger M.F., Faruk Senan N.A., O Reilly O.M., Lotz J.C., Minimizing Errors Associated with Calculating the Helical Axis of Spinal Motion", Journal of Biomechanics 43(14): (2010) d. Kennedy A., Coughlin D.G., Metzger M.F., Pearle A.D., Lotz J.C., Feeley B.T., Biomechanical Evaluation of Pediatric ACL Reconstruction Techniques, The American Journal of Sports Medicine 39(5): (2011). 3. Recently, my lab has demonstrated the importance of vitamin D for bone healing after fusion surgery. Rates of vitamin D deficiency and insufficient have been increasingly reported among otherwise health population. Previous studies have shown that inadequate serum levels of vitamin D have a significant impact on bone health; however, prior to our research, there was little to no published data on the causal effect of inadequate serum levels of vitamin on the success of establishing solid bony union after a spinal fusion procedure. Our data revealed the importance of having adequate levels of vitamin D, which yielded a higher fusion success rate and a stiffer, denser fusion mass. Clinically, our work demonstrates the importance of checking metabolic factors prior to surgery. This work is disseminated through the publications listed in my personal statement and other that are currently in progress. Complete list of Published Work in MyBibliography: D. Research Support Ongoing Research Support New Investigator Grant Kremen (PI) 07/01/15-06/30/16 Summary: Orthopaedic Research and Education Foundation The effect of Hamstring Tendon Autograft Harvest on the Restoration of Knee Stability in the Setting of Anterior Cruciate Ligament Rupture and Concurrent Medial Collateral Ligament Injury The goal of this project is to study the contribution of the gracilis and semitendinosus tendons to coronal and rotational stability of the knee in the setting of an ACL reconstruction with concurrent MCL injury. Research Grant Welch (PI) 07/01/15-06/30/15 Össur Summary: The Effect of Dynamic Bracing on Articular Contact Pressures in PCL Deficient Knees The goal of this project is to investigate whether dynamic PCL braces normalize compartment pressures in PCL deficient knees. Research Grant Alayan (PI) 05/01/15-04/30/15 Acumed, LLC Buried Fixation of Patella Fractures: A Biomechanical Investigation Summary: The goal of this study is to determine whether a novel patellar fixation method, that may reduce complication rates and minimize patient discomfort, provides equivalent or better stability when compared to more traditional means of repair. New Investigator Grant Metzger (PI) 11/01/14-10/31/15 North American Spine Society The Impact of Type II Diabetes on Bone Metabolism and Growth after Spinal Fusion Summary: This study investigates whether type II diabetes inhibits the formation of a solid bony union after spinal fusion surgery through a reduction in growth factors critical for bone formation New Investigator Grant Metzger (PI) 08/01/14-07/31/16

4 Scoliosis Research Society The Impact of Type I Diabetes on Bone Metabolism and Growth after Spinal Fusion Summary: This study investigates whether type I diabetes inhibits the formation of a solid bony union after spinal fusion surgery through a reduction in growth factors critical for bone formation Research Grant Metzger (PI) 7/01/12-12/31/15 Medtronic Spine Biomechanical Analysis of Direct Lateral Interbody Fusion (DLIF) Strategies for Adjacent Segment Degeneration in the Lumbar Spine Summary: This study analyzes the biomechanical effects of direct lateral interbody fixation constructs on levels adjacent to an existing fusion Completed Research Support Exploratory Grant Acosta (PI) 01/01/11-10/01/12 Scoliosis Research Society Improving Bone Formation in Osteoporosis through Mechanical Signaling Pathways Summary: This study investigated the responsiveness of MSCs and osteoblasts derived from osteoporotic human bone to both biochemical and mechanical signals. Exploratory Grant Metzger (PI) 07/01/11-06/30/12 Scoliosis Research Society Grant The Relationship between Experimental Serum Vitamin D Levels and Spinal Fusion Strength: a Quantitative Analysis Summary: This study investigated whether serum vitamin D levels affect the outcome of spinal fusions. Research Grant Metzger (PI) 07/01/11-12/01/12 Stryker Spine Biomechanical Analysis of the Effect of Different Instrumentation Techniques on Adjacent Level Stability after Long Segment Instrumentation of the Thoracic Spine Summary: This study analyzed the effect of posterior segmental construct stiffness on the stability of the proximal adjacent, un-instrumented segment in a multilevel thoracic spinal fusion model. Hansjorg Wyss Research Grant Metzger (PI) 09/01/11-04/30/12 AOSpine Does Sacral Geometry Affect Biomechanical Behavior and Facet Forces after Total Disc Replacement at the Lumbosacral Junction? Summary: This study investigated how the morphology of the lumbosacral junction influences the kinematics of motion preservation devices. R43 NS Metzger (PI) 07/01/03-06/31/04 Interventional Applications of Shape Memory Polymer Foam Summary: This project initiated the work on the SMP foam actuator (structure and properties) for the application applied to an aneurysm/avm occlusion device. R43 EB Metzger (PI) 09/01/04-08/31/05 Polymer Actuator for Peripheral Vessel Thrombectomy

5 Summary: This project applied the SMP foams to actuators designed for removing blockages in the peripheral vasculature. Role: Co-I