Sant Lab

Developing Biomimetic Microenvironments for Regenerative Therapies

Department of Pharmaceutical Sciences, University of Pittsburgh, PA

 

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  Research Interests

 

Engineering Three-Dimensional (3D) Tissue Models

In the pharmaceutical companies, cell-based assays are routinely used for screening drug safety and efficacy. However, traditional two-dimensional (2D) cell culture techniques often fail to recapitulate microenvironmental context and relevant complexity of tissues in vivo leading to poor predictions about drug effectiveness and response in clinical trials. Cancer is perfect example of a complex disease where tumor microenvironment plays important role in tumor progression, metastasis and invasion Despite the amount of efforts and money invested in the drug development, success of the majority of clinical trials remains poor due to lack of well-defined, reproducible in vitro 3D models based on human cells as well as failure of in vivo animal models to recapitulate human pathophysiology. I will approach these problems by engineering 3D tissue models that will allow understanding of cell-cell interaction, cell-matrix interaction, and cell-ECM interactions. We will use microfabrication, tissue engineering, materials science and drug delivery principles to control cellular microenvironments and develop regenerative therapies.

 

 

Controlled Drug delivery

I also envision that integrating controlled release strategies for growth factors and cytokines within scaffold-based approach may provide multifunctional platforms for regenerative medicine. Embryonic stem cells (ESCs) have great potential as cell sources for tissue engineering and regenerative medicine due to both, their self-renewal and multi-lineage differentiation capacity. Despite advances in the field of stem cell biology, major challenges remain before stem cells can be widely used for therapeutic purposes. One challenge is to develop reproducible methods to control stem cell growth and differentiation. Recent advances in micro- and nanofabrication techniques and material chemistry are geared to provide well defined cellular spatial organization. Apart from adequate mechanical, structural and topographical cues, temporal and spatial supply of morphogenic signals can be critical for the success of tissue engineering and stem cell therapy. This can be achieved by sequential and controlled delivery of growth factors incorporated in tissue engineered scaffolds. I would like to exploit my expertise in controlled release systems and micro/nanofabrication techniques to develop complex tissue analogs with spatiotemporal control over biochemical, mechanical and structural properties.

Our collaborators

Steffi Oesterreich, PhD, Professor

Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Magee-Womens Research Institute

 

Paul Johnston, PhD, Research Associate Professor

Department of Pharmaceutical Sciences, University of Pittsburgh

 

Lisa Rohan, PhD, Associate Professor

Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh

 

K. Suresh Babu, PhD, Assistant Professor

Centre for Nano Sciences & Technology Madanjeet School of Green Energy Technologies

 

Julie Phillipi, PhD, Assistant Professor

McGowan Institute for Regenerative Medicine, Thoracic Aortic Disease Research Laboratory

 

Tara Meyer, PhD, Associate Professor

Dept. of Chemistry University of Pittsburgh

 

Sharmila M. Mukhopadhyay, PhD, Professor

Mechanical & Materials Engineering Wright State University

 

Charles Sfeir, DDS, PhD, Associate Professor

Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine

 

Elia Beniash, PhD,  Associate Professor

Department of Oral Biology, University of Pittsburgh School of Dental Medicine

 

Sachin Velankar, PhD, Associate Professor

Chemical and Petroleum Engineering, Chemical and Petroleum Engineering

 

Kerry Empey, PharmD, PhD, Assistant Professor

School of Pharmacy, University of Pittsburgh

 

Thanks to the funding!