Effect
of biomechanical forces on vascular pathophysiology
Vascular
Tissue Engineering
Tissue
Engineered Blood Vessel
A biological
blood vessel is being developed to achieve long-term patency in the rat model
and will be subsequently translated to the porcine model. The blood vessel is
a "biological equivalent" to autologous arteries from a mechanical and
biofunctional perspective. This vessel is being generated by seeding precursor
cells within a tubular bioerodible thermoplastic elastomer designed to micromechanically
transmit appropriate stresses to the generating vessel during culture in vitro
and to withstand systemic circulation after in-vivo implantation. The in vitro
culture period may require specific mechanical training protocols that are currently
being studied to direct appropriate cell differentiation and expression of matrix
components. To that effect, progenitor cells are being stimulated by three different
mechanical forces that are normally present in the vascular system (cyclic strain,
cyclic pressure, shear stress). The cyclic strain and shear stress are produced
using commercially available systems from Flexcell International. The cyclic pressure
is produced with a system we developed in our laboratory (Fig. 1). These experiments
will help to elucidate the potential of mechanical forces to drive the differentiation
of progenitor cells towards vascular smooth muscle and endothelial cells.
Full Report.
Citations
Aortic
Graft Interposition
Video (150 MB)
Development
and assessment of a novel seeding device for tubular scaffolds
One
of the challenges in the tissue engineering of tubular tissues and organs is the
efficient seeding of porous scaffolds with the desired cell type and density in
a short period of time, without affecting cell viability. Though different seeding
techniques have been investigated, a fast, reproducible, and efficient bulk seeding
method with uniform cellular distribution has yet to be reported. We developed
and analyzed a novel seeding device utilizing the synergistic effects of vacuum,
centrifugal force and flow. The device allows porous tubular scaffolds to be uniformly
bulk seeded as well as luminally surface-seeded with cells. Biomaterials
27 (2006) 48-63-4870.
Urethral
Biomechanics and Function Ex Vivo
This
project is a collaborative effort of the departments of surgery, bioengineering,
urology, and pharmacology aimed towards understanding the effects of various disease
states on the urethra. The urethra is part of the lower urinary tract where its
role is to provide a tight mucosal seal during the bladder storage, as well as
a controlled conduit for urine to exit the body during voiding. The urethra is
a highly complex organ with many facets: neural innervation, smooth and striated
muscle layers and extracellular matrix, comprised mostly of collagen. In order
for the lower urinary tract to function normally, all three of these components
must be intact for successful bladder-urethra coordination.
While the diseased
bladder has extensively been studied in the past, our major focus is the alteration
of the biomechanical properties and neuro-pharmacological function of the urethra
in diabetes mellitus (DM), stress urinary incontinence (SUI) induced by vaginal
distension, and spinal cord injury (SCI). What happens to the lower urinary tract
in these cases? Briefly, in DM, the bladder becomes grossly distended and hypomotile,
while patients may experience urinary retention or incontinence. For SCI, patients
suffer from two phases: an areflexic bladder phase, which occurs instantly after
upper thoracic spinal injury (a.k.a spinal shock phase), and a hypereflexic bladder
and detrusor-sphincter dyssinergia phase, where the bladder is very motile and
is not communicating with the urethra, resulting in simultaneous contractions
between the bladder and urethra. Finally, SUI induced by birth trauma is thought
to be due to a weak urethral sphincter damaged by vaginal delivery.
In
vivo experiments in various animal models have aided in the understanding of the
changes in bladder function and bladder-urethra communication from disease and
dysfunction. Unfortunately, the in vivo models for the urethra are limited to
the information that can be provided. Thus, our laboratory is interested in an
ex vivo model used to study urethral biomechanics and neuro-pharmacological function.
The current vascular perfusion system was modified for urethral studies. Pressure
was applied statically with a reservoir attached to a calibrated ringstand and
the distal end clamped. The outer diameter is measured with a helium-neon laser
micrometer at proximal, middle, and distal portions due to urethral heterogenous
nature (Figure 2 and 3). A
physiologic environment was maintained with roller pump continuously circulating
a bath of media through a water bath and continuously bubbling the media with
95% oxygen and 5% carbon dioxide.
With
this system, we are able to gather the pressure-diameter data and calculate both
compliance and beta stiffness values. Assuming incompressibility, the thickness
may be gather from histology and utilized to find the inner diameter in order
to derive circumferential stress-strain curves, as well as incremental elastic
moduli values. Our laboratory has the ability to assess the biomechanical properties
in three different states: baseline (where no agents are added to the bath to
induce or inhibit a muscular response), active (where agents are added to contract
the muscle prior to mechanical testing), and passive (where agents are added to
the bath to inhibit a muscular response; Figure 4). 
Results
of these studies are compared to in vivo results of leak point pressure studies
and micro-tip catheter studies. Identifying changes both in vivo and ex vivo will
aid our understanding of urethral physiology in health and disease.
Citations.
