Dr. Robert L. Sah
receives
Young Investigator Award
Dr.
Robert L. Sah, Professor at Bioengineering, an affiliate of the department of
orthopaedics, and a member of the Whitaker Institute of Biomedical
Engineering, received the 2001 Young Investigator Award from the American
Academy of Orthopaedic Surgeons. The award was sponsored by the Kappa Delta
Sorority, which established in 1947 the first award ever created to honor
achievements in the field of orthopaedic research.
The award was
given for a series of studies that Dr. Sah conducted during the past eight
years in the field of cartilage tissue engineering. He delivered his award
presentation entitled “Articular Cartilage Tissue Engineering: Biological
and Biomechanical Foundations”.
There has
been a growing interest in the tissue engineering to repair damaged joint
cartilage during the past decade. While several methods, such as autologous
chondrocyte transplantation and osteochondral allografting, are used
clinically, follow-up studies in animals have shown that the repair tissue
does not have the durability of normal articular cartilage.
This has
created what Dr. Sah terms “an urgent need” to determine the cellular,
biochemical and physical conditions that will foster cartilage regeneration,
repair and long-term stability. And that has been the focus of his research.
Successful
tissue engineering therapy for a cartilage defect requires the integration of
the repair tissue with the host tissue and the filling of the bulk of the
defect with tissue that is characteristic of normal cartilage. This involves
the process of cell adhesion, migration, proliferation, and the formation and
remodeling of matrix material. Dr. Sah’s research has been directed at
determining what conditions of factors might enhance or deter these processes.
His first
objective was to discover which matrix remodeling mechanisms encourage
integration. He found that adhesion could be advanced or inhibited by
biochemical regulation of the chodrocytes in cartilage.
Dr.
Sah also found that collagen synthesis and crosslinking play an important role
in the development of adhesive strength. Collagen synthesis was proportional
to the adhesion that developed, he reported. On the other hand, he found that
inhibition of crosslinking during culture by inclusion of ß-aminoproprionitrile
completely inhibited adhesion.
The second
objective of his research was to analyze the interaction of transplanted
chondrocytes with a cartilage surface and their biological behavior at that
surface. Dr. Sah invented an in vitro
system to study chondrocyte transplantation and attachment to cartilage.
The results
of his study “indicate that the number of chondrocytes transplanted into and
attached to a cartilage defect can greatly affect matrix synthesis, which may
enhance repair,” Dr. Sah said. Dr. Sah also found that increased seeding
time made the chondrocytes more resistant to detachment from the cartilage.
This suggests that it may be beneficial to allow the cells to stabilize for
some time in the absence of applied load after transplantation, he said.
Another
objective of D. Sah’s research was to determine the effect that static
compression has on integration. He found that stresses as low as 0.06-0-24 Mpa
resulted in >50percent inhibition of biosynthesis or proliferation by the
transplanted chondrocytes.
“The
knowledge of the magnitude of the effect provides us with biomechanical
criteria for beginning to optimize the tightness of the fit of a cell-laden
cartilaginous construct into an articular defect and for developing
post-operative rehabilitation protocols,” Dr. Sah said.
Dr. Sah’s
final objective is to define the properties of articular cartilage at the
tissue length scale. Working with rabbits, Dr. Sah undertook tests to localize
and measure the degree of degeneration across the joint surface after the
induction of osteoarthritis and the performance of anterior cruciate ligament
transaction (ACLT). Gray-scale images of articular surfaces painted with India
ink were processed so that areas of normal cartilage gave a relatively high
reflectance score.
The reflectance score decreased as a traditional
morphological grade of degeneration increased, Dr. Sah reported. In areas that
were found to degenerate, ACLT led to a ~30 percent decrease in reflectance
score. In the tibial plateaus, ACLT caused significant degeneration in the
areas covered by the meniscus but not in the uncovered areas, he added.
“This identification and the characterization of
cartilage areas that are prone to degeneration should be useful for further
analysis of the biochemical and biomechanical mechanisms in osteoarthritis and
for the efficacy of therapeutic interventions,” Dr. Sah said.
Working with
both bovine and human tissues, Dr. Sah also developed a new method to
determine the compressive properties of cartilage at different depths from the
articular surface. Using fluorescently stained cells as intrinsic tissue
markers, he was able to measure intra-tissue deformation.
The
compressive stiffness of cartilage was found to be 20 times higher in the deep
regions of cartilage than in the surface regions. The low stiffness may be
central to improving the congruity between opposing cartilage surfaces.
Our warmest
congratulations to Dr. Sah for his well-deserved reception of this prestigious
award and best wishes for his further successes in this important area of
research!
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