Research Projects
1. Advanced hydrogel engineering for 3D culture and morphogenesis2. Cell-type-specific signaling in 3D co-cultures3. Spatially patterned 3D bioinks to control liver organoids growth4. Biomaterial for corneal endothelial monolayer transplantation and graft integrationPrevious Research Projects
Synthetic hydrogel for spatio-temporal control of liver cells differentiation
Liver
cholangiocytes form an intricate network of bile ducts to enable proper liver
function; yet, recapitulating human stem cell differentiation to cholangiocytes
in vitro requires Notch signaling and soluble ligands do not activate the Notch
pathway. To overcome these limitations, jagged1 is immobilized on a chemically
defined hyaluronan to specifically differentiate human embryonic stem
cell-derived hepatoblasts to cholangiocytes. Hepatoblasts cultured on the
jagged1-hydrogels upregulate Notch target genes and express key cholangiocyte
markers including cystic fibrosis transmembrane conductance regulator.
Moreover, cholangiocytes adopt morphological changes that resemble liver
biliary structures. To emulate natural biliary system development, a new
strategy is developed to achieve spatiotemporal control over the Jagged1–Notch2
interaction: jagged1 is first caged with a photocleavable streptavidin and then
it is uncaged photochemically to restore the biological function of Jagged1,
which is confirmed with Notch2 activation in a fluorescent reporter cell line.
Moreover, the differentiation of human embryonic stem cell-derived hepatoblasts
to cholangiocytes is temporally controlled with photochemical uncaging of this
streptavidin-Jagged1-immobilized hyaluronan hydrogel. This strategy defines a
framework to control protein signaling in time and space and specifically for
Notch signaling for ultimate use in regenerative medicine strategies of the
liver.
Bioactive,
hybrid crosslinked hydrogel for human corneal tissue growth ad transplantation
The
transplantation of tissue-engineered primary HCEC monolayer is a potential option
to treat corneal endothelium associated blindness. We designed a robust
hydrogel thin film that (i) allows primary human corneal endothelial cell growth
and monolayer formation (ii) is mechanically robust to survive rupture during transplantation
(iii) and enzymatically cleavable to allow gradual dissolution following transplantation.
We discovered that activation of the supramolecular chain associations in form
of hydrogen bonding in gelatin methacrylate (GelMA) at 4℃ followed by light
triggered crosslinking could lead to remarkable increase in the strength of GelMA
hydrogel. The presence of low temperature-induced physical network of gelatin triple
helices coupled with microstructural changes in the hydrogel improved the
subsequent UV covalent crosslinking reactions, which imparted excellent
strength to hydrogels. The primary human corneal endothelial cell monolayers
grown on 1 µm pillars of square-array GelMA films demonstrated improved ZO1 and
Na+/K+-ATPase expression, higher cell density and
homogeneity of cell size, which are indications of functionally-superior
monolayers. GelMA films were transplanted in rabbit animal models to
demonstrate that they were non-cytotoxic and they could gradually dissolve over
the period of 12 weeks.
High resolution hydrogel topographies
Micro- and nano-topography on cell culture dishes surface also enhanced proliferation and functional markers of donor-derived primary human corneal endothelial cells.
Engineering a
“Disease in a Dish” model to evaluate corneal cell therapy for Fuchs Dystrophy

Fuchs dystrophy – a degenerative disease of corneal endothelial
cells -affects millions of people worldwide. Cell therapy is one potential treatment
options for Fuchs. We developed a new method to recreate Fuchs environment in a
dish by controlled melting of the micropatterned polystyrene surfaces at the
glass transition temperature of the polymer. We used this approach to recreate
the early stage and late-stage Fuchs disease environment in a dish and injected
cells on them to study the regeneration of corneal endothelial monolayer. The primary human corneal
endothelial cells were unable to form a monolayer in cell injection therapy
approach on densely-packed synthetic guttata, which mimicked the late stage Fuchs.
However, the cells could form a monolayer and express ZO1 on dome-shaped sparsely-spaced
synthetic guttata micro-structures of a lower height, mimicking the early stage
Fuchs. This research suggested that the cell therapy approach is
more likely to succeed in early stage Fuchs patients, as compared to late-stage
patients. These findings have been reproduced by other groups by using actual Fuchs
affected corneas. My research was the first instance of applying micro-fabrication
and polymer surface design to recreate Fuchs disease environment that could
accurately predict cell therapy outcomes.
COLLABORATIONS
Dr. Rizwan has established collaborations with a number of renowned labs in the areas of materials engineering, cell biology, and chemistry to accomplish the vision of Instructive Biomaterials Lab.