Laurencin, Cato T.
University Professor and Chair, Biomedical Engineering
Biomaterials, Polymer Synthesis, Tissue Engineering, Drug Delivery, Nanotechnology
Bioreactor Related Research
<br/><br/>There are currently two ongoing bioreactor-related research programs in our
laboratory funded by the National Science Foundation (NSF) and National Aeronautics
and Space Administration (NASA). A multidisciplinary approach is taken to design,
fabricate and optimize three-dimensional (3-D) biodegradable poly (lactide-co-glycolide)
(PLAGA) based scaffold in a dynamic flow environment in NASA rotating bioreactors
for bone tissue engineering. Specifically, we exposed the 3-D scaffold to fluid
and nutrient flux via placement in a dynamic flow environment in NASA rotating
bioreactors and seek to gain a more fundamental understanding of the manner
in which cells interact with these degradable polymeric scaffolds in a dynamic
flow environment in NASA rotating bioreactors.
<br/><br/>We also seek to develop a novel 3-D biodegradable polyphosphazene based scaffold
in a dynamic flow environment in NASA rotating bioreactors suitable for bone
tissue engineering. We will design, fabricate, characterize, and optimize 3-D
polyphosphazene scaffolds for bone tissue engineering under a dynamic flow environment
in NASA rotating bioreactors.
<br/><br/>Our interdisciplinary projects address fundamental issues facing bone remodeling
and formation, particularly regarding the effects of an in vitro dynamic flow
environment in bioreactors on bone cell biology and bone formation in vivo.
Results from these studies will serve as the foundation for future work aimed
at exploring the effect of dynamic flow environment on bone healing and remodeling,
and for optimizing bioreactor tissue engineering of bone.
Tissue Engineering of Bone
<br/><br/>The goal of this work is to develop synthetic alternatives to orthopaedic tissues
such as bone, ligament, and cartilage. Once implanted, the presence of cells
and growth factors will initiate bone regeneration throughout the 3-D pore network.
As regeneration continues, the matrix is slowly resorbed by the body. Upon complete
degradation, the implant site is filled with newly regenerated bone and free
of any residual polymer.
<br/><br/>Using the biodegradable polymer poly (lactide-co-glycolide), we have developed
a series of 3-dimensional porous structures based on microsphere technology.
In combination with bone morphogenetic proteins and osteoblasts, these matrices
will serve as scaffolds for bone regeneration.
<br/><br/>Our research also focuses on the development and evaluation of polyphosphazene-ceramic
composites that could be used as scaffolds for bone tissue engineering.
<br/><br/>In studies examining cell growth on these matrices, we have utilized an osteoblast
cell lines as well as bone cells isolated from rat calvaria to create a model
system for cell growth on bioerodable materials. This image shows osteoblasts
growing on the surface of our 3-D microsphere matrix. It is interesting to note
that the cells are growing in a circumferential pattern due to the structure
of the matrix.
Tissue Engineering of Ligament
<br/><br/>The anterior cruciate ligament (ACL) is the most commonly injured ligament
of the knee, due to inherently poor healing potential and limited vascularization
ACL ruptures do not heal and surgical replacement is often required. Our laboratory
has produced a cell-seeded, degradable, three-dimensional (3-D) scaffold for
ACL replacement and regeneration. Three-dimensional braiding techniques have
been used to create a scaffold with optimized pore size for cell proliferation
and tissue ingrowth, resistance to wear and rupture, and mechanical properties
comparable to natural ACL. Presently, we are optimizing this structure to improve
the biomechanical properties, adjust degradation time, and enhance the cell
proliferation and tissue regeneration abilities of the implant. These changes
will result in an implant that behaves more like natural ligament and enhances
regeneration without rupturing after implantation.
<br/><br/>Tissue engineering scaffolds fabricated from nanofibers are gaining importance
due to their unique similarity to extracellular matrices, high porosity, and
ease of fabrication. Also the nanofibers have an advantage of enormous surface
area due to very high length to diameter ratio of the fibers. A very elegant
process to make the nanofiber scaffolds is by subjecting the polymer solution
or melts to very high potential difference. A variety of parameters such concentration,
melt viscosity, potential difference etc. can be optimized to obtain desired
diameter and morphology of the resultant nanofibers. Further these nanofibers
can also be formed to three dimensional scaffolds that can be used as the scaffold
for tissue engineering.
<br/><br/>In our laboratory, we are investigating the different ways to fabricate two
and three dimensional nanofibers from a variety of biodegradable and non biodegradable
polymers that could be used for a various biomedical applications.
<br/><br/>Funded by the National Materials Testing Bed Inc., Department of Defense, we
are also studying the release of growth factors from nanofibers for skin regeneration
in the case of burn victims and diabetic ulcer patients. In this work we are
optimizing the various parameters associated with electrospinning for obtaining
growth factor loaded nanofibers of consistent diameters for optimal release
of growth factors for faster regeneration of the skin.
<br/><br/>We have also developed a microsphere based drug delivery system for delivering
radiosensitizers for the treatment of musculoskeletal tumors and rheumatoid