Former CELer Terri-Ann Kelly, PhD Profiled on WPI Website

Former CELer Terri-Ann Kelly, PhD Profiled on WPI Website

Dr. Kelly graduated from Columbia in 2006 with her thesis titled: “Functional Tissue Engineering of Articular Cartilage: Characterization and Optimization of Chondrocyte-Seeded Agarose Hydrogels .” She now serves as lead engineer at EpiBone, spearheading the research and development of cartilage tissue products.

Eben Estell Defends his Thesis!

Eben Estell Defends his Thesis!

Eben defended his thesis, titled “Modulation of Synoviocyte Mechanotransduction in the Osteoarthritic Environment” on Friday, December 7. He will be doing his post-doc at Maine Medical Center Research Institute. Congratulations, Dr. Estell!

Thesis Abstract: The synovium is a specialized connective tissue that encapsulates diarthrodial joints like the knee, maintaining a low-friction environment for the articulating surfaces within. This tissue plays a key role in homeostasis by regulating solute transport in and out of the joint, and secreting paracrine and lubricating factors into the synovial fluid. The predominant cell type in the synovium is the fibroblast-like synoviocyte (FLS), which resides on the intimal surface of the tissue and produces lubricating molecules such as hyaluronan. Because these cells directly face the synovial fluid and apposing tissue surfaces within the joint, they are exposed to a dynamic environment of mechanical stimuli generated during daily activity. This dissertation addresses the global hypothesis that FLS are mechanosensitive to distinct modes of shear stress generated in the knee during articulation, and that modulation of this sensitivity by chemical and physical factors of the osteoarthritic (OA) environment contributes to disease progression.

Previous work has demonstrated that fluid-induced shear stress, generated as synovial fluid redistributes within the capsule during articulation, is a relevant mechanical stimulus for FLS. Exposure of FLS to fluid shear has been shown to modulate downstream functions such as lubricant secretion and the release of degradative matrix-metalloproteinases as induced by the cytokine interleukin-1, the latter indicating a link between mechanotransduction and the inflammatory environment of OA. The first goal of this dissertation was to further elucidate the process of mechanotransduction by characterizing the upstream response of FLS to fluid shear, to determine the influence of interleukin-1, and investigate known potentiators of mechanotransduction as potential mechanisms of the observed cytokine modulation. The work presented herein demonstrates for the first time a robust calcium signaling response of FLS to fluid shear, a key upstream event in the mechanotransduction of physical stimuli. Furthermore, the modulation of key aspects of this response were significantly altered by pre-exposure to interleukin-1, indicating a pathologic modulation of normal mechanosensing in the OA environment. This modulation was observed in both juvenile bovine and human FLS from healthy and OA donors, and was found to be potentiated by increases in intercellular communication via gap junctions as well as modulation of the primary cilia of individual cells.

In addition to chemical factors such as cytokines, the degradation of cartilage itself produces a physical factor, in the form of wear particles, that perpetuates the OA disease state. As degrading cartilage surfaces continue to grind against each other within the joint, these particles are released into the synovial fluid and attach to the synovium. We have previously shown in a bovine model that attachment of cartilage wear particles (CWP) to FLS monolayers in static culture induces release of pro-inflammatory mediators of OA. The second goal of this dissertation was to employ a similar in vitro model with human FLS to confirm CWP modulation of downstream function in static culture, as well as calcium signaling response when exposed to fluid shear. To this end, we found that CWP attachment to human FLS monolayers induces similar pro-inflammatory release products as observed in bovine models in static culture, and significantly modulates the calcium signaling response to fluid shear.

In areas of the articulating capsule where apposing tissues slide in direct contact with each other, shear stress generated by these frictional interactions may provide a physical stimulus distinct from fluid-induced shear stress. In this case of direct interaction between surfaces, the tissue-level frictional properties may affect the magnitude of shear stress presented to the cells within the intimal layer. While previous work has characterized synovium friction properties in sliding contact against glass, relatively little is known of synovium tribology in native tissue configurations, the influence of pathologic conditions such as CWP attachment, or the consequences for mechanotransduction of FLS within the tissue. The third goal of this dissertation is thus to characterize the effect of CWP on both tissue-level mechanical properties and cell-level mechanotransduction under sliding contact. The work herein presents consistently low friction properties for synovium against other tissues within the joint such as cartilage and demonstrates a significant increase in these properties when CWP are attached. A novel bioreactor was developed to characterize the effect of sliding contact on downstream functions of FLS within explant tissues, where initial results indicated an increase in metabolic activity in FLS exposed to sliding contact against cartilage.

The research presented in this dissertation further elucidates the processes of normal synoviocyte mechanotransduction, and by demonstrating that key chemical and physical factors of the OA environment modulate both cell and tissue-level functional properties, sheds light on the mechanisms by which the synovium contributes to disease progression. This sets the foundation for future work into synovium mechanotransduction in response to distinct physical stimuli and the relationship with tissue-level mechanical properties, and points towards clinical interventions that seek to restore the normal mechanical environment of the joint.

Robert Stefani Publishes New Functional Synovium-based Model of OA in Tissue Engineering Part A

Robert Stefani Publishes New Functional Synovium-based Model of OA in Tissue Engineering Part A

Robert Stefani publishes a novel in vitro tissue engineered synovium model, validated against native explants, to investigate the structure-function of synovium through quantitative solute transport measures. The synovium envelops the diarthrodial joint and plays a key regulatory role in defining the composition of the synovial fluid through filtration and biosynthesis of critical boundary lubricants. Synovium changes often precede cartilage damage in osteoarthritis, but the mechanism by which it may contribute to disease progression has not yet been elucidated. It is anticipated that this model will support efforts to develop more effective strategies aimed at restoring joint health.

Andy J. Lee Presents Research at BMES 2018

Andy J. Lee Presents Research at BMES 2018

CEL graduate student Andy Lee presented his research at the BMES Annual Meeting in Atlanta, Georgia. In his talk, titled “SB431542-Encapsulated Microspheres as a Strategy to Prevent Arthrofibrosis,” he discussed a novel approach to deliver a sensitive TGF-β inhibitor to the synovial capsule.

Clark T. Hung Co-Inventor of Award Winning Technology

Clark T. Hung Co-Inventor of Award Winning Technology

The Missouri Osteochondral Preservation System (MOPS) won the 2018 best technology in sports medicine award, presented by Orthopedics This Week. The technology significantly extends the life of tissue allografts, with the added benefits of the use of closed containers, serum-free media that includes dexamethasone, and the ability to be stored at room temperature. MOPS was developed by MTF Biologics in conjunction with Missouri Orthopedic Institute & ConMed, with CEL Director Clark T. Hung and former CEL doctoral student Eric Lima as co-inventors and engineers.

Saiti Halder Invited to Present at SciSymp2018 Conference

Saiti Halder Invited to Present at SciSymp2018 Conference

Saiti Halder, an undergraduate researcher in CEL, will be presenting her work at the Scientista Symposium Poster Fair and Competition in Times Square on April 14. The symposium is part of SciSymp18, which celebrates "Innovation in STEM - Scientistas Advancing the Field." Great job, Saiti!

CEL Team Presents at Orthopedic Research Society Meeting

CEL Team Presents at Orthopedic Research Society Meeting

Cellular Engineering Laboratory graduate students Robert Stefani and Eben Estell gave podium presentations at the Orthopedic Research Society Annual Meeting in New Orleans. Associate research scientist Dr. Andrea Tan, graduate student Jae Han Lee, and research assistant William Yu presented posters of their research during the meeting.

Unwinding on the Bourbon Street balcony of Dr. Eddie Schwartz. Thank you for hosting us!

Unwinding on the Bourbon Street balcony of Dr. Eddie Schwartz. Thank you for hosting us!

CEL Hosts "Inside Engineering"

 
 

On Saturday, October 21, 2017, CEL hosted high school students from the Bridge to Enter Advanced Mathematics (BEAM) program as they learned about topics "Inside Engineering." With diabetes as a disease model, students were introduced to the potential for using hydrogel beads and capsules for therapeutic approaches to manage the disease. Students participated in a hands on experiment making solid alginate beads that can be used for cell or drug delivery.

Alginate is a biopolymer hydrogel that is able to crosslink internally and externally to form alginate beads and capsules. After this formation, alginate can be used to encapsulate cells which protects them from immune cells and release of cell products.

Sofia Barbosa and Lance Murphy Represent Columbia at International Seminar for Engineering Leaders

Sofia Barbosa '20 and Lance Murphy '18 attended the International Seminar for Engineering Leaders, held at Pontificia Universidad Católica de Chile in Santiago, Chile from September 24-30, 2017. They are two of three engineering undergraduates representing Columbia University at the conference, which was attended by 800 students from around the globe.

Sofia (mentored by Andrea Tan) and Lance (mentored by Eben Estell) gave an oral presentation on their lab research examining the effects of cell synchronization on cellular mechanotransduction and biosynthetic output in tissue engineered cartilage. 

Check out their introductory video, explaining their motivations for research and representing Columbia at the conference!