Indwelling Neural Implants Strategies for Contending with the

In Vivo Environment - 1st Edition

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 To Shirley Sue Reichert.
Mother. Advisor. Friend.

© 2008 by Taylor & Francis Group, LLC

Contents
Series Preface............................................................................................................ix
Preface ......................................................................................................................xi
Acknowledgments.................................................................................................. xiii
Editor ....................................................................................................................... xv
Contributors ...........................................................................................................xvii

PART I

Chapter 1 Overview of Wound Healing in Different Tissue Types......................3

John D. Stroncek and W. Monty Reichert

PART II

Chapter 2 Signal Considerations for Chronically Implanted Electrodes for

Brain Interfacing ................................................................................ 41
Warren M. Grill

Chapter 3 Thermal Considerations for the Design of an Implanted

Cortical Brain–Machine Interface (BMI).......................................... 63
Patrick D. Wolf

PART III

Chapter 4 In Vitro Models for Neuroelectrodes: A Paradigm for

Studying Tissue–Materials Interactions in the Brain ........................ 89
Vadim Polikov, Michelle Block, Cen Zhang, W. Monty Reichert,
and J. S. Hong

Chapter 5 In Vivo Solute Diffusivity in Brain Tissue Surrounding

Indwelling Neural Implants ............................................................. 117
Michael J. Bridge and Patrick A. Tresco

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© 2008 by Taylor & Francis Group, LLC

viii Indwelling Neural Implants

PART IV

Chapter 6 A Molecular Perspective on Understanding and Modulating

the Performance of Chronic Central Nervous System (CNS)
Recording Electrodes ....................................................................... 151
Wei He and Ravi V. Bellamkonda

Chapter 7 Soft, Fuzzy, and Bioactive Conducting Polymers for Improving

the Chronic Performance of Neural Prosthetic Devices .................. 177
Dong-Hwan Kim, Sarah Richardson-Burns, Laura Povlich,
Mohammad Reza Abidian, Sarah Spanninga,
Jeffrey L. Hendricks, and David C. Martin

Chapter 8 Strategies for Regeneration and Repair in the Injured Central

Nervous System................................................................................ 221
Molly S. Shoichet, Ciara C. Tate, M. Douglas Baumann,
and Michelle C. LaPlaca

© 2008 by Taylor & Francis Group, LLC

Series Preface
The Frontiers in Neuroengineering series presents the insights of experts on emerg-
ing experimental techniques and theoretical concepts that are or will be at the van-
guard of neuroscience. Books in the series cover topics ranging from methods to
investigate apoptosis to modern techniques for neural ensemble recordings in behav-
ing animals. The series also covers new and exciting multidisciplinary areas of brain
research, such as computational neuroscience and neuroengineering, and describes
breakthroughs in fields such as insect sensory neuroscience, primate audition, and
biomedical engineering. The goal is for this series to be the reference that every
neuroscientist uses to become acquainted with new methodologies in brain research.
These books can be used by graduate students and postdoctoral fellows who are
looking for guidance to begin a new line of research.
Each book is edited by an expert and consists of chapters written by the leaders
in a particular field. Books are richly illustrated and contain comprehensive bibliog-
raphies. Chapters provide substantial background material relevant to the particular
subject. Hence, the books in this series are not the usual type of method books. They
contain detailed “tricks of the trade” and information as to where particular meth-
ods can be safely applied. In addition, they include information about where to buy
equipment and Web sites helpful in solving both practical and theoretical problems.
Finally, they present detailed discussions of the present knowledge of the field and
where it should go.
We hope that, as the volumes become available, that our efforts as well as those
of, the publisher, the book editors, and the individual authors will contribute to the
further development of brain research. The extent to which we achieve this goal will
be determined by the utility of these books.

Sidney A. Simon, Ph.D.

Miguel A.L. Nicolelis, M.D., Ph.D.
Series Editors

ix

© 2008 by Taylor & Francis Group, LLC

Preface
In the quarter century since the idea of using neural signals to control an external
effector prosthetic first surfaced, enormous strides have been made in understand-
ing the neuronal circuitry of the relevant brain structures, developing the computer
hardware and software algorithms capable of transforming the neuronal potentials
into control signals, and engineering high-density recording arrays. In contrast, a
number of fundamental and unresolved questions remain as to the source of signal
degradation in chronically implanted neuroelectrodes. Is it the result of insertion
trauma, micromotion, mechanical mismatch, or simply the consequences of glial
scar formation arising from a normal chronic foreign body response? What roles
do electrode size, shape, surface chemistry, mechanical impedance, and insulating
material play? What is the fate of neurons adjacent to the recording site as the signal
degrades? Are they silenced, killed, or just pushed out of the way by the glial scar?
Do these effects arise from inhibitory cues expressed in the glial scar or by the
inflammatory molecules released into the vicinity of the electrode? What happens
when one introduces devices that stimulate the surrounding brain tissue? What is
the impact on the surrounding tissue from telemetric communication and on-chip
processing? What are the best methods for intervening in the repair of trauma caused
by device implantation? At this point, nobody really knows; however, if answers are
not found, then the field will never progress from its current state of the occasional
well-publicized success to widespread use in humans.
This text entitled Indwelling Neural Implants: Strategies for Contending with
the In Vivo Environment is a compendium of contributions from a number of noted
experts who are working in the field of neuroprosethetics and tissue repair. These
experts were requested to contribute chapters that focused on this general theme, but
I also encouraged them to elaborate on specific aspects important to future therapies
for the response of central nervous system (CNS) tissue to implants. Combined, this
text is a unique contribution to the CNS literature and one that certainly fits the
theme of Taylor & Francis/CRC’s Frontiers in Neuroengineering series.
The central feature of these chapters is the impact, characterization, and miti-
gation of the healing of the tissue that surrounds the implant. By and large, these
chapters speak for themselves; however, the text can be divided thematically into
four parts.
Part I reviews and highlights the differences between wound healing in the
CNS, peripheral nervous system, subcutaneous tissue, and bone. While healing in
these tissues shares a number of molecular and cellular phenomena, differences arise
rapidly as one progresses from the initial trauma to inflammation to repair. This
chapter serves as the phenomenological basis for the subsequent contributions.
Part II by Warren Gill and Patrick Wolf of Duke University is composed of two
chapters that present the performance of implanted neuroprosthetics from the com-
ponents perspective. Compared to the earliest “passive” recording electrodes, neu-
roprosthetics are increasingly “active” implants that impact the surrounding tissue

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© 2008 by Taylor & Francis Group, LLC

xii Indwelling Neural Implants

chemically, mechanically, thermally, and electrically. These chapters present per-

formance issues that arise from chronic tissue stimulation and heating effects from
on-chip and telemetric processing.
In Part III, Jau-Shyong Hong of the National Institute of Environmental Health
Sciences and Patrick Tresco of the University of Utah contribute, respectively, in vitro
and in vivo approaches to assessing the CNS wound healing response to materials.
Dr. Hong’s chapter compares the complexity and the level of information obtained
from the different cell culture and organotypic models. Dr. Tresco describes the
application and numerical modeling of his chronic hollow-fiber-membrane in vivo
implant model for assessing molecular transport to the surrounding brain tissue.
Part IV consists of three chapters that describe molecular and materials strate-
gies for intervening in CNS wound repair and enhancing the electrical communica-
tion between the electrode surface and the surrounding tissue. The chapter by Ravi
Bellamkonda of the Georgia Institute of Technology stresses molecular approaches
for biasing cellular migration during the various stages of healing around implanted
electrodes to encourage greater and more specific cell–surface interaction. The
chapter by David Martin of the University of Michigan presents the deployment
and characterization of novel conducting polymers to facilitate the communication
between the electrode surface and the adjacent neurons. Finally, the chapter by Molly
Shoichet of the University of Toronto and Michelle LaPlaca of the Georgia Institute
of Technology takes the broader view of addressing the sequelae of CNS traumatic
injury (of which neuroprosthesis insertion is a specific example) and presents novel
strategies for nerve regeneration and repair.

William M. Reichert, Ph.D.

Duke University
Durham, North Carolina

© 2008 by Taylor & Francis Group, LLC

Acknowledgments
I extend my sincere appreciation to the lead authors and their coauthors for the hard
work in preparing their fine contributions. I also thank series editors Sidney Simon
and Miguel Nicolelis of Duke University for the opportunity to compile this text.

© 2008 by Taylor & Francis Group, LLC

Editor
William M. Reichert, Ph.D., was born in San Francisco, California, grew up in
Ann Arbor, Michigan, and lives in Hillsborough, North Carolina, with his wife
Kate, his son Stephen, and three dogs and a cat. He also has a daughter Elizabeth and
a stepdaughter Miranda. He graduated with a B.A. in Biology and Chemistry from
Gustavus Adolphus College in 1975, was a part-time student, a hospital technician
and bartender for a couple of years, and received a doctorate in Macromolecular Sci-
ence and Engineering from the University of Michigan in 1982. He was a National
Institutes of Health (NIH) National Research Service Award Postdoctoral Fellow, a
Whitaker Fellow, and a NIH New Investigator Fellow at the University of Utah in
the Department of Bioengineering, where he “learned the ropes” from Professors
Joe Andrade and Art Janata.
He joined the Department of Biomedical Engineering at Duke University in 1989
and is currently Professor of Biomedical Engineering and Chemistry, and Director of
the Center for Biomolecular and Tissue Engineering. He is a fellow of the American
Institute of Medical and Biological Engineering and is on the editorial boards for the
Journal of Biomedical Materials Research and Langmuir. He is program director of
an NIH predoctoral training grant that supports graduate fellowships in biotechnol-
ogy and has been a steadfast advocate for promoting underrepresented minorities
in engineering graduate education, receiving the Catalyst for Institutional Change
from Quality Education for Minorities (QEM) Network, Pioneer Award from the
Samuel DuBois Cook Society, and the Dean’s Award for Excellence in Mentoring.
His current research interests are wound healing-related implant failure, biosensors,
vascular graft endothelialization, and cytokine profiling. He has trained a number of
doctoral and postdoctoral students now working in academics and industry, he has
published nearly 100 scientific papers, and he holds patents for multianalyte wave-
guide sensors and protein detection arrays.

xv

© 2008 by Taylor & Francis Group, LLC

Contributors
Mohammad Reza Abidian Jeffrey L. Hendricks
Department of Biomedical Engineering Department of Biomedical Engineering
University of Michigan University of Michigan
Ann Arbor, Michigan Ann Arbor, Michigan

M. Douglas Baumann J. S. Hong

Department of Chemical Engineering Neuropharmacology Section
and Applied Chemistry National Institute of Environmental
University of Toronto Health Sciences
Toronto, Ontario, Canada National Institutes of Health
Research Triangle Park, North Carolina
Ravi V. Bellamkonda
Coulter Department of Biomedical Dong-Hwan Kim
Engineering Department of Biomedical Engineering
Georgia Institute of Technology/Emory Duke University
University Durham, North Carolina
Atlanta, Georgia Michelle C. LaPlaca
Coulter Department of Biomedical
Michelle Block
Engineering
Neuropharmacology Section
Georgia Institute of Technology/Emory
National Institute of Environmental
University
Health Sciences
Atlanta, Georgia
National Institutes of Health
Research Triangle Park, North Carolina David C. Martin
Department of Biomedical Engineering
Michael J. Bridge Biomedical Engineering and
Department of Bioengineering Macromolecular Science and
University of Utah Engineering
Salt Lake City, Utah University of Michigan
Ann Arbor, Michigan
Warren M. Grill
Department of Biomedical Engineering Vadim Polikov
Duke University Department of Biomedical Engineering
Durham, North Carolina Duke University
Durham, North Carolina
Wei He
Coulter Department of Biomedical Laura Povlich
Engineering Macromolecular Science and
Georgia Institute of Technology/Emory Engineering
University University of Michigan
Atlanta, Georgia Ann Arbor, Michigan

xvii

© 2008 by Taylor & Francis Group, LLC

xviii Indwelling Neural Implants

Sarah Richardson-Burns Ciara C. Tate

Department of Biomedical Engineering Coulter Department of Biomedical
University of Michigan Engineering
Ann Arbor, Michigan Georgia Institute of Technology/Emory
University
Molly S. Shoichet Atlanta, Georgia
Department of Chemical Engineering Patrick A. Tresco
and Applied Chemistry Department of Bioengineering
University of Toronto University of Utah
Toronto, Ontario, Canada Salt Lake City, Utah

Sarah Spanninga Patrick D. Wolf

Macromolecular Science and Department of Biomedical Engineering
Engineering Duke University
University of Michigan Durham, North Carolina
Ann Arbor, Michigan Cen Zhang
Neuropharmacology Section
John D. Stroncek National Institute of Environmental
Department of Biomedical Engineering Health Sciences
Duke University National Institutes of Health
Durham, North Carolina Research Triangle Park, North Carolina

© 2008 by Taylor & Francis Group, LLC

Part I

© 2008 by Taylor & Francis Group, LLC

11/7/2007 6:27:39 AM
 1 Overview of Wound
Healing in Different
Tissue Types
John D. Stroncek and W. Monty Reichert

CONTENTS
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1.1 INTRODUCTION AND OVERVIEW

The inevitable response to any implant is wound healing comprised of hemostasis,
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number of reviews [1–6] and a multitude of primary articles address this issue for

© 2008 by Taylor & Francis Group, LLC

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4 Indwelling Neural Implants

implanted sensors, primarily glucose electrodes; however, there has been only one
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