Our current research objectives are designed to address four areas of complexities
both in applied therapeutics and in basic biomedical sciences.
Development of micro-fabricated polymer structures with pre-designed spatio-temporal
patterning of bio-factors to study stem cell differentiation
A major effort in the lab is in the area of microfabricated scaffold structures
for stem cell engineering. This is a unique combination of developing manufacturing
techniques to create spatially and temporally patterned microenvironments and
studying the fundamental mechanisms of cell-environment interaction in the
context of stem cell differentiation into multiple tissue lineages. With funding
from the Whitaker Foundation (Bioengineering Research Grant) and the National
Science Foundation (SGER) we are developing, in collaboration with Dr. Shaochen
Chen at UT Austin, a layer-by-layer micro-manufacturing process using laser
photo-crosslinkable polymers that would allow us to spatially embed/pattern
various growth factors (either as soluble entities or encapsulated within controlled
release polymer particles) at pre-designed spatial location within a porous
tissue-engineering scaffold. This 3D laser-scanning stereolithography (3D-LSL)
concept would allow us to create three dimensional scaffold structures containing
different microenvironments in different regions and enable us to differentiate
pluripotent stem cells into multiple lineages within a single scaffold. Initial
results from this work have been accepted for publication in The Journal of
Biomedical Materials Research. Here we showed that precise, pre-designed spatial
distribution of multiple factors can be achieved within a single cell scaffold
and functionalities like growth factor gradients and precise internal architectures
can also be created within these polymer structures.
Ultimately our goal is to create hybrid tissues with pre-designed pattern
of cells and extracellular matrices, similar to the process of organ regeneration.
This could not only provide us with organotypic models to understand cell behavior
under complex microenvironments but also one day allow us to fabricate functional
complex tissues having multiple cell types for on demand transplantation or
in-vitro cell function studies (e.g. drug or vaccine screening, liver functions
etc.). Two specific directions that this project is pursuing are (a) creating
bone and cartilage within the same structure starting from a single stem cell
population and (b) fabrication of a lymph-node like structure containing T,
B and dendritic cells that is capable of antigen processing and presentation
with an ultimately goal of generating a high-throughput vaccine/drug screening
system.
References:
- Y. Liu, G. Mapili, G Suhali, S. Chen and K. Roy, A digital micro-mirror
based device for the fabrication of spatially
patterned tissue engineering scaffolds, J Biomed Mater Res A. Jan 27; [Epub
ahead of print] (2006)
- G. Mapili, Y. Liu, S. Chen and K. Roy, Laser-layered microfabrication
of spatially patterned functionalized tissue-engineering
scaffolds, J Biomed Mater Res B Appl Biomater. Nov;75(2):414-24 (2005)
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