Lianna Gangi received Honorable Mention on her 2020 National Science Foundation Graduate Research Fellowship Program (NSF-GRFP) proposal titled Bioengineering model of synovium to study osteoarthritic pain. Congratulations, Lianna!
We would also like to congratulate fellow BME graduate students Ethan Bendau and McKenzie Sup!
Jack Rogot won 3rd place at the Poster Competition during the Engineering in Medicine Symposium held at Columbia University on February 20, 2020.
Articular cartilage injuries are a common source of joint pain and dysfunction. We hypothesized that pulsed electromagnetic fields (PEMFs) would improve growth and healing of tissue engineered cartilage grafts in a time‐ and direction‐dependent manner. PEMF stimulation of engineered cartilage constructs was first evaluated in vitro using passaged adult canine chondrocytes embedded in an agarose hydrogel scaffold. PEMF coils oriented parallel to the articular surface induced superior repair stiffness compared to both perpendicular PEMF (p=0.026) and control (p=0.012). This was correlated with increased GAG deposition in both parallel and perpendicular PEMF orientations compared to control (p=0.010 and 0.028, respectively). Following in vitro optimization, the potential clinical translation of PEMF was evaluated in a preliminary in vivo preclinical adult canine model. Engineered osteochondral constructs (∅ 6 mm x 6 mm thick, devitalized bone base) were cultured to maturity and implanted into focal defects created in the stifle (knee) joint. To assess expedited early repair, animals were assessed after a 3‐month recovery period, with microfracture repairs serving as an additional clinical control. In vivo, PEMF led to a greater likelihood of normal chondrocyte (OR: 2.5, p=0.051) and proteoglycan (OR: 5.0, p=0.013) histological scores in engineered constructs. Interestingly, engineered constructs outperformed microfracture in clinical scoring, regardless of PEMF treatment (p<0.05). Overall, the studies provided evidence that PEMF stimulation enhanced engineered cartilage growth and repair, demonstrating a potential low‐cost, low‐risk, non‐invasive treatment modality for expediting early cartilage repair.
Articular cartilage defects are a common source of joint pain and dysfunction. We hypothesized that sustained low-dose dexamethasone (DEX) delivery via an acellular osteochondral implant would have a dual pro-anabolic and anti-catabolic effect, both supporting the functional integrity of adjacent graft and host tissue while also attenuating inflammation caused by iatrogenic injury. An acellular agarose hydrogel carrier with embedded DEX-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (DLMS) was developed to provide sustained release for at least 99 days. The DLMS implant was first evaluated in an in vitro pro-inflammatory model of cartilage degradation. The implant was chondroprotective, as indicated by maintenance of Young's modulus (EY) (p=0.92) and GAG content (p=1.0) in the presence of interleukin-1β insult. In a subsequent preliminary in vivo experiment, an osteochondral autograft transfer was performed using a pre-clinical canine model. DLMS implants were press-fit into the autograft donor site and compared to intra-articular DEX injection (INJ) or no DEX (CTL). Functional scores for DLMS animals returned to baseline (p=0.39), whereas CTL and INJ remained significantly worse at 6 months (p<0.05). DLMS knees were significantly more likely to have improved OARSI scores for proteoglycan, chondrocyte, and collagen pathology (p<0.05). However, no significant improvements in synovial fluid cytokine content were observed. In conclusion, utilizing a targeted DLMS implant, we observed in vitro chondroprotection in the presence of IL-1-induced degradation and improved in vivo functional outcomes. These improved outcomes were correlated with superior histological scores but not necessarily a dampened inflammatory response, suggesting a primarily pro-anabolic effect.
Hagar Kenawy (CEL, Columbia University) and Timothy Jacobsen (Chahine Lab, Columbia University) received the ORS PSRS Trainee Poster Award for Outstanding Scientific Research at the 5th International Spine Research Symposium in Skytop, Pennsylvania. Congratulations!
Rob defended his thesis, titled “Role of the Synovial Membrane in Osteoarthritis Treatment and Cartilage Repair” on Friday, November 8. Congratulations, Dr. Stefani!
Columbia University Department of Biomedical Engineering kicked off it’s 20th Anniversary Celebration on Friday with an Alumni Reception in Carleton Lounge. Following welcoming remarks by Dean Mary C. Boyce and X. Edward Guo, Professor of Biomedical Engineering and Department Chair, Professor Hung and CEL alumni shared memories from past 20 years of Columbia BME as well as a discussion of the bright future of the department. Featured in the discussion were CEL alumni: Eric Lima, Andrea Tan, and Terri-Ann Kelly.
(L to R) Dean Mary C. Boyce, Professor Clark T. Hung, Dr. Andrea Tan, Dr. Terri-Ann Kelly, Dr. Eric Lima, and Professor X. Edward Guo
Congratulations to CEL undergrad, Neeraj Sakhrani, who presented his summer research at the Poster Grand Rounds: Topic C – Musculoskeletal Medicine at the 2019 Rehabilitation Research Day on September 13, 2019.
Title: Towards an In Vitro Model of Diabetic Osteoarthritis and Insulin Resistance in the Synovial Joint
Authors: Neeraj Sakhrani, Lance A. Murphy, Andy J. Lee, Robert M. Stefani, Eric J. Semler, Roshan P. Shah, Christopher J. Visco, Xiaoning Yuan, Clark T. Hung
May 18, 2019
Professor Clark T. Hung, in his first presentation with his joint appointment in Orthopaedic Surgery, delivered a research seminar at UPenn this past weekend. He was awarded the Department of Orthopedic Surgery Distinguished Alumni Award (scientist). Dr. Robert L. Mauck, a previous graduate student in CEL, is now Director of the McKay Orthopaedic Research Laboratory at UPenn.
Authors: Estell EG, Silverstein AM, Stefani RM, Lee AJ, Murphy LA, Shah RP, Ateshian GA, Hung CT.
Abstract: The synovium plays a key role in the development of osteoarthritis, as evidenced by pathological changes to the tissue observed in both early and late stages of the disease. One such change is the attachment of cartilage wear particles to the synovial intima. While this phenomenon has been well observed clinically, little is known of the biological effects that such particles have on resident cells in the synovium. The present work investigates the hypothesis that cartilage wear particles elicit a pro-inflammatory response in diseased and healthy humanfibroblast-like synoviocytes, like that induced by key cytokines in osteoarthritis. Fibroblast-like synoviocytes from 15 osteoarthritic humandonors and a subset of 3 non-osteoarthritic donors were exposed to cartilage wear particles, interleukin-1α or tumor necrosis factor-α for 6 days and analyzed for proliferation, matrix production, and release of pro-inflammatory mediators and degradative enzymes. Wear particlessignificantly increased proliferation and release of nitric oxide, interleukin-6 and -8, and matrix metalloproteinase-9, -10, and -13 in osteoarthritic synoviocytes, mirroring the effects of both cytokines, with similar trends in non-osteoarthritic cells. These results suggest that cartilage wear particles are a relevant physical factor in the osteoarthritic environment, perpetuating the pro-inflammatory and pro-degradative cascade by modulating synoviocyte behavior at early and late stages of the disease. Future work points to therapeutic strategies for slowing disease progression that target cell-particle interactions.
Title: On the Biomechanics of Cardiac S-Looping in the Chick: Insights From Modeling and Perturbation Studies
Authors: Ashok Ramasubramanian, Xavier Capaldi, Sarah A. Bradner and Lianna Gangi
Abstract: Cardiac looping is an important embryonic developmental stage where the primitive heart tube (HT) twists into a configuration that more closely resembles the mature heart. Improper looping leads to congenital defects. Using the chick embryo as the experimental model, we study cardiac s-looping wherein the primitive ventricle, which lay superior to the atrium, now assumes its definitive position inferior to it. This process results in a heart loop that is no longer planar with the inflow and outflow tracts now lying in adjacent planes. We investigate the biomechanics of s-looping and use modeling to understand the nonlinear and time-variant morphogenetic shape changes. We developed physical and finite element models and validated the models using perturbation studies. The results from experiments and models show how force actuators such as bending of the embryonic dorsal wall (cervical flexure), rotation around the body axis (embryo torsion), and HT growth interact to produce the heart loop. Using model-based and experimental data, we present an improved hypothesis for early cardiac s-looping.
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.
