Glaucoma is an age-related, neurodegenerative disease and the leading cause of irreversible blindness. The vision loss in glaucoma is caused by permanent optic nerve damage due to increased intraocular pressure (IOP). IOP is the most critical and the only modifiable risk factor for glaucoma and is controlled by the outflow of the aqueous humor primarily through the conventional outflow pathway. In collaboration with Drs. John Danias (SUNY Downstate Health Sciences University), Yiqin Du (University of Pittsburgh), and Karen Torrejon (Glauconix Biosciences), we have developed artificial conventional outflow systems (ACOS) using primary or stem cell-derived human trabecular meshwork (HTM) and/or human Schlemm’s canal (HSC) cells. These ACOS provide a new avenue to understand outflow physiology and facilitate high-throughput gene and drug screening, advancing drug discovery and stem cell replacement therapy for glaucoma.

image of Bioengineering Ocular Outflow Physiology for High-throughput Drug and Gene Screening

Salivary gland dysfunction is associated with aging, radiation therapy for head and neck cancers, and the autoimmune disorder, Sjögren’s syndrome. Fibrosis occurs in salivary glands of afflicted individuals, inhibiting tissue regeneration. Salivary gland stroma contains tissue-resident mesenchymal stromal cells (MSCs), which have anti-fibrotic potential. To test the hypothesis that exogenous MSCs can revert endogenous fibrotic MSCs to a homeostatic state, reducing fibrosis, we developed fabrication methods to reproducibly produce cryogenic hydrogel nanofiber sponge scaffolds that mimic the ECM topography and biomechanical properties of the salivary gland tissue. These scaffolds support maintenance of salivary gland tissue-resident MSC phenotype and self-organization of stromal and epithelial cells in vitro. In collaboration with Dr. Mindy Larsen (University at Albany), this project lays a foundation for bioengineering healthy and fibrotic salivary gland tissues in vitro and delivery of MSCs in vivo to reduce salivary gland fibrosis, leading to salivary gland tissue regeneration.

image of Nanofiber Scaffolds for Salivary Gland Regeneration

Alginate hydrogel microtubes are a promising advance for 3D cell culture, organoid production, tissue engineering, and cell-replacement therapy. We have developed multiple technologies for reproducible fabrication of stable hydrogel microtubes and have demonstrated the feasibility of employing alginate hydrogel microtubes for maintenance of stem cell pluripotency, directed differentiation of stem cells, study of cell-cell interactions, self-organization of stromal and epithelial cells, and generation of organoids. Examples include embryoid-bodies-in-µ-tube, brown-fat-in-µ-tube, lens-in--µ-tube, and salivary-gland-in-µ-tube. Hydrogel microtubes provide an accessible, reproducible, scalable organoid culture system for disease modeling, drug screening, tissue engineering and regenerative medicine.

image of Hydrogel Microtubes for Organoid Cultures

Controlled-release sutures for advanced wound healing and other medical needs are a major scientific breakthrough, poised to benefit people around the world. Controlled-release sutures will have time-release growth factors, which will greatly expedite the healing process while minimizing risk of infection and reducing scar formation. This project is a collaboration with StemCultures to develop a functional prototype of degradable controlled-release sutures, facilitating manufacturing and commercialization.

While large-scale bioreactors for automated production of therapeutic proteins are well established, similar reactors for selection, activation, expansion and differentiation of cell therapy products, including immuno-oncology and regenerative medicine applications are lacking. The ability to generate and manufacture up to 100 billion cells per patient is a major challenge in cell therapy, and the potential shift from autologous (patient-derived) to allogenic (off-the-shelf) therapies, while reducing the cost of goods, will further increase the demands for cellular biomanufacturing.

Engineered T cells, particularly chimeric antigen receptor (CAR) T cells and natural killer cells, have great potential in immuno-oncology. Currently there is limited process development for T cell culture, partially due to the lack of appropriate bioreactors with process control capabilities. The long-term goal of this project is to develop bioprocess methods capable of large-scale, cost-effective, reproducible manufacturing of high quality cells with uniform and well-defined characteristics. This project is a collaborative effort with Sepragen led by Professor Sharfstein.


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