Cell and Tissue Engineering Lab

Research

 
Microfluidic assay development

Our current research efforts are focused on developing next generation of microfluidic devices which can integrate multiple cell types and controlled microenvironments at physiologically relevant spatio-temporal scales. These devices enable user-defined control of the distance and type of interaction between different cell populations, along with spatio-temporal delivery of biochemical and biophysical stimuli, either stand-alone or in combination, to different cell populations. Developing such state-of-the-art microfluidic platforms for mathematical modeling, measuring, and imaging cell-cell signaling will help improve our understanding of the effects of cell-cell (same type or different types) interactions on cellular behavior, tissue morphogenesis, disease pathogenesis, and synthetic biology. Such devices may also act as surrogate organ platforms for preclinical drug and toxicity testing, and clinical diagnostics assays of patient samples, as an early step toward personalized medicine. We have several ongoing projects in the lab using state-of-the-art microfluidic platforms.

 

Stem cells based regenerative medicine approaches

The utility of stem cells has been the focus of recent research for their ability to yield large quantities of mature neural and glial cells, on-demand for transplantation purposes. Stem cells offer a potentially unlimited source of precursor cells for therapeutic applications. We hypothesize that tissue engineering approaches combining 3D injectable scaffolds and diffusive signaling cues offer a sustainable biomimetic microenvironment for enhanced differentiation and assembly of specialized cells and organotypic tissues. Our recent studies have shown that stem cells could be differentiated into specific neural (motor neurons, dopaminergic neurons, etc.) and glial lineages by manipulating their microenvironment. For example, the presence of 3D collagen scaffold and retinoic acid (RA) promoted stem cell differentiation into predominant motor neurons lineage, while 3D matrigel scaffold and combination of RA and sonic hedgehog promoted dopamine producing neurons. We also found that tissue biomechanics and biomolecular concentrations play an important role in regulating this differentiation and maturation process. Our current studies are aimed at understanding the molecular mechanisms driving this differentiation process. These findings not only serve as an experimental model for early differentiation events in lieu of in vivo studies, but also are of tremendous relevance for neurodegenerative diseases modeling, drug and toxicology screening, and regenerative medicine therapies.

 

Structural and mechanical properties of soft materials

We routinely develop novel synthetic or biological hierarchical scaffolds to mimic the complexity of native tissues, and thus act as delivery vehicles for cells, growth factors and mechanical stimuli at the desired site. The physico-chemical characteristics of these functional macromolecular hetero-structures are imaged and quantified using a wide range of characterization tools. These scaffolds typically consist of nanoparticles or nano-fibers, suspended in a soft matrix (e.g. collagen, elastin, hyaluronic acid, cellulose), with the scaffold properties varied by adjusting temperature, concentration of nanoparticles, percentage of cross-linkers, and matrix-to-fluid ratio. The best way to characterize the influence of above-mentioned parameters on the structural and mechanical integrity of these scaffolds is by using an atomic force microscope (AFM). With support from National Science Foundation, we recently acquired an AFM, integrated with an inverted fluorescence microscope, for high-resolution imaging and mechanotransduction experiments. The high-resolution imaging capability of an AFM enables real-time surface analysis and manipulation at sub-molecular level, which is not possible with other optical or scanning electron microscope techniques. On the other hand, the versatile and modular cantilever-tip system enables low-noise force spectroscopy measurements at various regions of the scaffold, thus measuring the Young’s modulus on the nanometer scale, without destructing the sample. AFM offers a powerful tool to map the mechanical properties of scaffolds characterized by structural variation, typical for biological applications and biomimicry, thus offering a powerful tool to bridge structure with properties. We also recently acquired a rheometer which can quantify the viscoelastic properties of soft gels and liquids over a wide range of experimental conditions.

Funded by Cleveland State University Research Foundation, National Science Foundation and National Institutes of Health