8:30 –
9:30
Nano and Microcrystalline Silicon
as a Diverse Biomaterial Platform
Jeffery L. Coffer, Ph.D.
Professor and Chair
Department of Chemistry
ABSTRACT: With a long–term interest in multifunctional
semiconducting nanostructures relevant to biomaterials, we seek to successfully
construct rapidly-adaptive platforms based on electrically-responsive,
mechanically-robust tunable artificial nanostructures that are not only
biocompatible, but furthermore bioactive, and whose activity can be altered not
only by physical dimension and chemical composition but external stimuli as
well. Recent focus has entailed studies of the bottom up synthesis of elemental
silicon dots and wires, top down fabrication of spongy porous Si structures,
and fundamental studies of surface modification and diffusion from these
matrices. Incorporation of the proper inorganic component to the nanostructures
brings mechanical strength and semiconductive character; Porosity allows for the
release of therapeutic release of useful substances from the material, as well
as proper vasculature & neural in-growth to the scaffold; in some cases,
composite formulation with biopolymers brings tunability to the structure in
terms of biodegradability. This presentation will provide examples from the
above categories, with discussion of material fabrication requirements,
structural characterization, and bio-relevant properties.
BIOGRAPHY: Jeff Coffer, a native of South Carolina, earned his B.S.
degree in Chemistry from Wofford College (SC) in 1982, a Ph.D. in inorganic
chemistry from the University of Wisconsin in 1987, and from 1987-1989 Dr.
Coffer was a postdoctoral fellow at the School of Chemical Sciences and
Materials Research Laboratory of the University of Illinois, Urbana-Champaign
. He joined the faculty of
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9:45 –
10:45
Engineering
of Ocular Drug Delivery Systems
Alan Weiner,
Ph.D.
Senior
Director, Development
Alcon
Research Ltd.
ABSTRACT: There
are a wide range of biomaterials that have been either commercialized or
studied in the human eye. Approved
devices for use or implantation in the eye include contact lenses, intraocular
lenses, scleral buckles and balloons, artificial prosthetics (i.e., whole or
partial eye), punctal plugs, intravitreal slow release devices, glaucoma
filtration shunts, scleral expanders, vitreous tamponades, viscoelastics,
ocular surface inserts and artificial cornea.
This broad historical experience with surgical procedures for correcting
disorders and diseases of the eye has fostered an extensive understanding of
biomaterial compatibility with ocular tissues.
An extension of this knowledge is increasingly being bridged with the
need to deliver therapeutic agents from such devices. For ocular therapy, potential
administration routes for drug delivery devices include topical, punctal,
subconjunctival, intravitreal, juxtascleral, intrascleral and subretinal as
well as parenteral administration, including oral. Engineering of these devices is dependant on
a) whether the need is for therapy of acute or chronic disease, b) the size or
volume allowable within the chosen tissue and c) drug diffusion or distribution
from the particular implant site to the site of action. Most challenging have been systems which
treat chronic diseases such as macular degeneration and neovascularization,
glaucoma, diabetic retinopathies, edema, and dry eye syndromes. For these applications ocular system designs
typically involve either reservoir or matrix drug delivery mechanisms. Reservoir systems generally provide more precise
rate control but often involve more complex surgical procedures for
implantation and removal. Erodible
matrix systems are usually dependant on more than one factor for rate control
(i.e. drug dissolution, drug release and polymer/excipient erosion) and may be
subject to restrictions of total drug loading.
This presentation will examine
the range of biomaterial systems, either marketed, in clinical trials, or in
preclinical experimental models, that facilitate drug delivery to ocular
tissues. The physiological challenges to
device retention and maintenance of effective drug delivery will be reviewed.
BIOGRAPHY: Dr. Alan Weiner is currently Senior
Director, Development at Alcon Research, Ltd. and is in charge of the groups
that develop the research formulations and dosage forms for Alcon’s
pharmaceutical and surgical therapeutic products, including drug delivery
systems. He has previously served there
as Senior Director Glaucoma Clinical Science, and as Director, Scientific Affairs and Market Development,
Glaucoma. Before
joining Alcon 10 years ago, Dr. Weiner was a founding scientist of two drug
delivery based companies - Escalon Ophthalmics and The Liposome Company, now
part of Elan Pharmaceuticals. Dr. Weiner
received his Ph.D. in Biochemistry from
**********************************************************************
11:00 –
12:00
Confocal Total
Internal Reflection Microscopy:
A Novel Technique
of Investigating Single Molecules in Tissue
Julian Borejdo,1
J. Talent,1
1Dept of Molecular Biology & Immunology
2Dept of Biochemistry
Mayo Clinic
ABSTRACT: Proteins in cells are present in micromolar concentrations. Observing kinetics of single protein molecules in vivo requires therefore that signal be collected from attoliter (10-18L) volume. Confocal Total Internal Reflection provides a way to obtain such data with high Signal-to-Noise. In this method, the observational volume is made shallow by illuminating sample with evanescent field produced by total internal reflection of the incident laser beam. A confocal aperture inserted in the image plane of the objective guarantees the small lateral dimensions of the observational volume. It is shown, by measuring diffusion of fluorescent microspheres, that the evanescent field is ~110 nm deep. 3.5 μm confocal aperture gives lateral dimensions of 120 nm x 120 nm, i.e. the observational volume of 1.5 attoL. The technique was applied to measuring kinetics of single myosin molecule in muscle fiber. Association-dissociation of myosin head was probed with rhodamine attached at Cys707 of the heavy chain of myosin, and the power stroke was probed with rhodamine attached to Cys73 of genetically engineered regulatory light chain exchanged into muscle. Fluorescence measured from the myofibrillar A-band was contributed by ~1-20 rhodamine molecules. Fluorescence decayed in a series of discrete steps, corresponding to bleaching of individual molecules of rhodamine. Signal was compared from myofibril in rigor and during isometric contraction. Shortening of myofibrils was prevented by light cross-linking with 1-ethyl-3-[3-dimethylamino)-propyl]-carbodiimide. Cross-bridge labeled at the head rotated at the rate approximately equal to the ATPase. Cross-bridge labeled at the lever arm rotated slower than the ATPase rate. These results suggest that during contraction of muscle fibers, hydrolysis of one ATP molecule does not always lead to a power stroke.
BIOGRAPHY: Julian Borejdo earned the B.A. and Ph.D.
degrees in Mathematics and Physics from
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1:30 –
2:15
Holographic
Visualization of 3D Data for Medical Applications
Harold R. “Skip” Garner, Jr., Ph.D.,
Bala Munjuluri, and Michael L. Huebschman
UT Southwestern
ABSTRACT: The display
of dynamic color holographic images is possible by computing the hologram of
objects in a three-dimensional scene and then transcribing the two-dimensional
digital hologram onto a digital micromirror system illuminated with coherent
light. Two proof-of-principle
instruments have been developed which, respectively, reconstruct real and virtual
images. This new, truly holographic 3-D
viewing system has a broad range of applications, including heads-up displays,
video games, television and workstations for medical applications – sonograms,
MRI, etc. This system can display any
3-D data, real or computationally synthesized, and can update the hologram of
moving objects in near-real time using new algorithms developed especially for
the display. The underlying process,
its characteristics, limitations and utility will be discussed. This technology forms the basis for a
potential new company, with the working name, Holomedix, that is focused on the
medical display applications market. Additional
information can be found on the www at http://innovation.swmed.edu and
in the following references:
1. Bala Munjuluri, Michael L. Huebschman, and Harold R. Garner, Rapid Hologram Updates for Real Time Volumetric Information Display, in press, Applied Optics
2.
Michael L. Huebschman, Bala Munjuluria, Jeremy Hunt, Harold R. Garner, Holographic
video display using digital micromirrors, in press, SPIE
3.
Michael L. Huebschman, Bala Munjuluri and
Harold R. Garner, Dynamic Holographic 3-D Image Projection, Optics Express,
Vol. 11, No. 5, 437-445, March 2003.
BIOGRAPHY: Skip received
his BS in Nuclear Engineering at the
Skip worked for 12 years at General
Atomics in
Skip currently holds the P. O’B. Montgomery,
M.D., Distinguished Chair, is a Professor of Biochemistry and Internal
Medicine, at UT Southwestern Medical Center.
He sits on numerous corporate advisory boards, advises for numerous
governmental agencies and has 15 issued patents.
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2:25 –
3:10
Tag-free Biosensors with Resonant Photonic Lattices
Debra Wawro, P.S. Priambodo, and Robert Magnusson
Resonant Sensors Incorporated
ABSTRACT: A new photonic sensor concept is presented for detection of biological and chemical agents. The heart of the sensor is a periodic dielectric waveguide in which resonant leaky modes are excited by an incident optical wave. Biochemical reactions occurring at the sensor’s surface cause changes in the reflection spectra (amplitude and phase) that are measured to identify the binding event without chemical tags. Numerous computed examples and experimental results illustrate key sensor properties and define promising paths for establishing useful sensor technology based on these ideas. The technology has broad applicability including homeland security, environmental and industrial monitoring and pharmaceutical drug development.
BIOGRAPHY: Debra Wawro
is founder and CEO of Resonant Sensors Incorporated, a newly formed optical
sensor company from the Arlington Technology Incubator at the
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3:30 –
4:05
Exploring Microgravity Bioreactors for Pancreatic Islet Cell Transplantation
Lynne P. Rutzky, Ph.D.
Associate Professor of Surgery
Division of Immunology and Organ
Transplantation
University of
ABTSRACT: Type I insulin dependent diabetes mellitus
remains a major cause of morbidity and mortality and therapy with exogenous
insulin only delays onset and severity of end organ complications, such as
kidney disease and vascular and peripheral nerve damage. While whole organ pancreas
transplant is a serious surgical risk, islet cell transplantation is cost
effective and less invasive procedure, which may help prevent future disease
complications. Recently, Shapiro’s (2000) steroid-free
BIOGRAPHY: Lynne P. Rutzky, Ph.D. is Associate Professor
of Surgery at The University of Texas Health Science Center-Houston Medical
School, Department of Surgery, Division of Immunology and Organ
Transplantation. Dr. Rutzky received a B.S. degree from The University of
Wisconsin-Madison and M.S. and Ph.D. degrees in Medical Microbiology from the
**********************************************************************
4:15 – 5:00
“Clinical Applications of Photochemical Bonding”
J. Lester Matthews, Ph.D.
President
MicroBioMed Corporation
ABSTRACT: Several
photochemicals have been evaluated for potential use in bonding and/or
cross-linking of animal structural proteins to achieve tissue repair; for
fabrication of tissue prostheses; or for anchoring of chemicals for control delivery
at select tissue sites. A major criterion in our selection was the excitation
wavelength of light required to activate the bonding process. Several UV
excited photochemicals show bonding properties but we elected to use visible
light excited species in order to minimize the effect of direct irradiation of
tissue with UV. The class of
photochemicals selected for complete evaluation are aqueous based
naphthalimides that exhibit low tissue toxicity and are excited by light in the
blue visible range. Naphthalimides can also be attached to other chemicals
using dark chemistry preserving the light response property of the
naphthalimide for subsequent use in tissue bonding. Naphthalimides can be used
in conjunction with various filler materials to improve adhesive properties
with uneven surfaces, tissue defects, and to improve the gap spanning potential
with minimal applied compression. The
addition of fillers either attached to naphthalimide or free in suspension with
naphthalimide have demonstrated greater efficiency in tissue bonding in either
a tissue overlapped or tissue abutted mode. Filler material may include
polysaccharides (i.e. chitosan, etc.), proteins (i.e. collagen,
fibrin/thrombin,etc.), or potentially other synthetic or biomaterials. Several
advantages to using chitosan-based naphthalamide formulations have been
demonstrated. First, overall tissue bond
strengths have been improved, both in a collagenous pericardial model as well
as in the adherence of a pericardial patch to the adventitial layer of a torn
arterial wall. Light exposure of the chitosan-bradsyl-naphthalimide prior to
application of the formulation to tissue has yielded bond strengths of 518 
160 g/cm2
enabling significant tissue bonding without requiring direct trans-illumination
of the tissue. Second, hemostasis is readily achieved. Alternatively, naphthalimide derivatives in
the dimer form demonstrate bond strengths of 1.8 kg/cm2 when
irradiated within the tissue. Cell culture data demonstrates that the chitosan-based
naphthalimide adhesive has an excellent biocompatibility profile and short term
studies in tissues show little or no inflammation. Long term studies of the
naphthalimide dimers in repaired sheep meniscus show no pathologic tissue
response or toxicity for two years duration, all treated animals functioning
normally following repair.
Our naphthalimide formulations have now been tested in a variety of tissues and potential clinical applications including: repair of torn meniscal tissue in the knee, stabilization of injected particles of collagen to treat incontinence, bonding of torn dura, delivery of drugs in local tissue sites such as anti-restenotic agents to coronary artery tissues, repair of corneal tear, bonding of synthetic materials such as nylon sheets to tissue, fabrication of artificial vessels using collagen sheets, anchoring of sunscreen materials to outer skin cells, repair of rabbit aorta capable of withstanding 1,200mm Hg perfusion pressure. The formulations work well with natural and synthetic films of collagen composition providing a means of obtaining marginal seals and elimination of the need for sutures. We are presently focused on two applications for ultimate evaluation by regulatory agencies of this new device formulation and seek partners for other activity.
BIOGRAPHY: Dr.
Matthews completed his B.S. and M.S. degrees in Biology at the