Description:

Design of Engineering Testbeds for Prostate and Breast Cancer Metastasis

In regenerative medicine, tissue engineering shows much promise for regenerating soft and hard tissues. Bone tissue engineering is particularly attractive for non-union defects. Our group has developed unique bio-mineralization routes for development of novel nanoclay scaffolds that use intercalated amino acids to initiate bone mineralization through vesicle delivery much like the biogenic bone mineralization processes. This biomimetically synthesized bone is also shown to exhibit a lower Ca/P stoichiometry characteristic of new-bone or remodeling bone. The remodeling bone is also a common site for colonization of cancer cells in metastasis stage from several primary site cancers. Bone is the preferred site of metastasis for prostate cancer and approximately 80% deaths suffered by prostate cancer patients result from skeletal metastases. Approximately 70% breast cancer patients eventually develop bone metastasis. At metastasis, drug treatments are often ineffective. Using the tissue engineering approaches that are closely guided by multiscale modeling and simulations for materials selection and scaffold design, we have designed an engineered test-bed of bone metastasis through use of nanoclay-hydroxyapatite(HAP) based nanocomposite polycaprolactone (PCL) scaffolds using a unique sequential culture (SC) procedure. Our experiments indicate that human mesenchymal stem cells (MSCs) enable newly formed bone extracellular matrix on PCL/ HAPClay scaffolds. These scaffolds when seeded through SC with prostate and breast cancer cells closely mimic early stage of osteoblastic cancer colonization by developing tight junction tumoroids and inducing late stage cancer or the mesenchymal to epithelial transition (MET). The gene expression data are indicative of enhanced MET, increased angiogenesis by hypoxia when cancer cells were sequentially cultured with MSCs in PCL/ HAPClay scaffolds. Nanomechanical experiments are conducted on the test-beds to study evolution of cancer mechanics and study the mechanobiological manifestations of cancer progression at metastasis. The nanoclay based testbed could be used for studying cancer cell biology in the early stage cell colonization and metastasis and in vitro testing of anticancer drugs in a humanoid environment.

Biography:
Dr. Kalpana Katti is a University Distinguished Professor in the Department of Civil and Environmental Engineering at North Dakota State University. She joined NDSU in 1997 after receiving a Ph.D. from University of Washington in Materials Science and Engineering. At NDSU she has established a state-of-the-art materials characterization laboratory that houses advanced nanomechanical and infrared spectroscopic equipment as well as a Tissue Engineering Laboratory. She has served as PI on infrastructure development grants bringing new advanced electron microscopes with federal funding that have led to significant expansion of the Electron Microscopy facility at NDSU. She also spearheaded a new doctoral program in Materials and Nanotechnology at NDSU which is offered since 2006. Her research in the field of Nanomaterials and Biomaterials is nationally an internationally recognized and has led to several discoveries and made important contributions to the field.
Dr Katti’s primary area of research is in tissue engineering, cancer scaffolds and biomimetics. The Katti group has developed novel nanoclay based nanocomposites for biomedical applications. In addition, experimental and modeling work done in this group has resulted in formulating the ‘altered phase theory’ of nanocomposites that describes the fundamental reasons of enhanced properties in nanoclay composites (polymer clay nanocomposites or PCNs). She has also led multiscale modeling and experimental studies on biological nanocomposite systems such as seashells and bone. Recently her group has successfully developed bone mimetic scaffolds that create cancer tumors in advanced stages of metastasis of cancer to bone thus enabling a humanoid testing of anticancer drugs and for understanding late stage cancer progression and developing new interventional technologies. She leads the NDSU Center for Engineered Cancer Test-Beds (CECT). Another important contribution from her group has been the understanding that mineral proximity influences mechanical property of polymers, proteins and biopolymers, which has large impact on understanding mechanics of engineered nanocomposites as well as biological materials such as seashells and bone. She has received research grants totaling about $5M since 2000. She has published 178 publications in Journals, conference proceedings and book chapters. She has received the most cited award from the journal Colloids and Interfaces for the 2004-2007 years. She is also a NSF CAREER awardee. She is an elected Fellow of the American Institute for Medical and Biological Engineering (AIMBE) for 2018. At NDSU she is engaged in promotion and tenure, teaching, NSF ADVANCE as part of the FORWARD team, high performance computing, faculty and administrator search committees and several other committees at department, college and university level. She received the Peltier award for innovations in teaching in 2007 and the 52nd faculty lectureship award in 2011. She is also the recipient of the Roon award from Federation of Coatings Technologies in 1999 and Presidential Scholar award from Microscopy Society of America in 1996.
Dr Katti is actively involved in several professional societies in leadership and service roles. At the Materials Research Society, she has chaired the Academic Affairs committee, chaired subcommittee on University Chapters, been a MRS Bulletin Organizer, participated in science advocacy through MRS congressional days in Washington DC and served on the New Products and Publications subcommittee of the MRS Publications Committee. Her involvement in other societies includes chairing the Biomechanics and Properties of Materials committees of Engineering Mechanics Institute of ASCE, as well as serving on molecular modeling and characterization committee of EMI and the Biomaterials committee of TMS. She regularly organizes symposia for MRS, TMS, and MS&T. She has given over 50 invited, keynote and plenary lectures at national and international conferences. She reviews papers and proposals for several publishers and federal agencies in the US, Europe, Australia, Asia and South America.