Andy successfully defended his thesis, titled “Strategies to Modulate the Joint Response to Pathological Mediators” on Tuesday, April 18.
Congratulations, Dr. Lee!
Huge shoutout to the following CEL Lab members for graduating this year:
Andy J. Lee: Ph.D., Biomedical Engineering
Matthew J. Pellicore: M. Phil., Biomedical Engineering
Howard J. Nicholson III: M.S., Biomedical Engineering
Neeraj Sakhrani: M.S., Biomedical Engineering
Maria Nuñez: B.S., Biomedical Engineering
Athena Pagon: B.S., Biomedical Engineering
Congratulations, everyone!
Howard Nicholson III presented research for SCHOLARTalks, an inaugural lightning talks program to highlight emerging faculty and scholar voices in research across all disciplines at Columbia University. The presentation was titled “Contribution of Blood Components to Cell Death in ACL Injury Through Ferroptotic Mechanisms.”
Congratulations, Howard!
Howard Nicholson III was awarded a National Science Foundation (NSF) Graduate Research Fellowship for his proposal titled “Bioengineering Studies of Primary ACL Repair: Structure-Function Relationships and Translation.”
Congratulations, Howard!
Neeraj Sakhrani and Co-Authors publish research article in Applied Sciences as part of the Special Issue: Effect of Electric Field on Stem Cells, Bone/Cartilage Cells, Neurons for Tissue Engineering and Regenerative Medicine. The manuscript is titled “Pulsed Electromagnetic Field Therapy and Direct Current Electric Field Modulation Promote the Migration of Fibroblast-like Synoviocytes to Accelerate Cartilage Repair In Vitro.” Co-Authors include: Robert M. Stefani, Stefania Setti, Ruggero Cadossi, Gerard A. Ateshian, and Clark T. Hung.
Congratulations, everyone!
Abstract: Articular cartilage injuries are a common source of joint pain and dysfunction. As articular cartilage is avascular, it exhibits a poor intrinsic healing capacity for self-repair. Clinically, osteochondral grafts are used to surgically restore the articular surface following injury. A significant challenge remains with the repair properties at the graft-host tissue interface as proper integration is critical toward restoring normal load distribution across the joint. A key to addressing poor tissue integration may involve optimizing mobilization of fibroblast-like synoviocytes (FLS) that exhibit chondrogenic potential and are derived from the adjacent synovium, the specialized connective tissue membrane that envelops the diarthrodial joint. Synovium-derived cells have been directly implicated in the native repair response of articular cartilage. Electrotherapeutics hold potential as low-cost, low-risk, non-invasive adjunctive therapies for promoting cartilage healing via cell-mediated repair. Pulsed electromagnetic fields (PEMFs) and applied direct current (DC) electric fields (EFs) via galvanotaxis are two potential therapeutic strategies to promote cartilage repair by stimulating the migration of FLS within a wound or defect site. PEMF chambers were calibrated to recapitulate clinical standards (1.5 ± 0.2 mT, 75 Hz, 1.3 ms duration). PEMF stimulation promoted bovine FLS migration using a 2D in vitro scratch assay to assess the rate of wound closure following cruciform injury. Galvanotaxis DC EF stimulation assisted FLS migration within a collagen hydrogel matrix in order to promote cartilage repair. A novel tissue-scale bioreactor capable of applying DC EFs in sterile culture conditions to 3D constructs was designed in order to track the increased recruitment of synovial repair cells via galvanotaxis from intact bovine synovium explants to the site of a cartilage wound injury. PEMF stimulation further modulated FLS migration into the bovine cartilage defect region. Biochemical composition, histological analysis, and gene expression revealed elevated GAG and collagen levels following PEMF treatment, indicative of its pro-anabolic effect. Together, PEMF and galvanotaxis DC EF modulation are electrotherapeutic strategies with complementary repair properties. Both procedures may enable direct migration or selective homing of target cells to defect sites, thus augmenting natural repair processes for improving cartilage repair and healing.
Ratna Sharma wins best poster at the Columbia Undergraduate Research Symposium! The symposium showcased the work of 150 students across multiple disciplines, with research encompassing STEM, social sciences, and humanities and the arts.
This summer, Ratna joined CEL under the advisement of Dr. Clark Hung and graduate student Neeraj Sakhrani. Her project involved investigating the effects of hyperglycemia on the function of fibroblast-like synoviocytes and its contribution to the pathogenesis of osteoarthritis. Her final poster was titled “High Glucose-Induced Oxidative Stress Impairs Proliferation and Migration of Healthy Human Synovial Fibroblasts in the Development of Diabetic Osteoarthritis.”
Congratulations, Ratna!
Aamna Siddiqui completes the Columbia University-Amazon Summer Undergraduate Research Experience (SURE) Program. As a SURE fellow, Aamna completed 10 weeks of research under the advisement of Dr. Clark Hung and graduate student Matthew Pellicore.
Aamna joined CEL from Virginia Commonwealth University. She is a rising senior majoring in Biomedical Engineering with a minor in Political Science. This summer, Aamna’s project involved investigating the effects of fluid shear on fibroblast-like synoviocytes, and how changes in primary cilia length and incidence may be involved. Her final poster, titled “Assessing Changes in Mechanosensitivity and Primary Cilia Incidence and Length in Fibroblast-like Synoviocytes in response to siRNA-mediated IFT88 knockdown”, was presented at the SURE 2022 Summer Symposium on August 3, 2022. Aamna’s project was awarded “Best Poster” for Poster Session A.
SURE is an initiative that began in 2021 with generous support from Amazon. The program aims to provide a unique summer research experience for a cohort of students from historically underrepresented backgrounds in STEM. In addition to the completion of a research project, fellows attended programming, lectures, and workshops focused on career, professional, and research skills development. The summer 2022 cohort included 50 fellows.
Congratulations, Aamna! Thank you for your hard work this summer!
The Hung Lab was featured in the Columbia Engineering Magazine: The Aging Issue.
The article, “Out with the Old” details the lab’s efforts in combating cartilage degeneration.
Andy Garcia was awarded a National Science Foundation (NSF) Graduate Research Fellowship for his proposal titled "Multiphasic Modeling of Synovium Structure-Function Relationships.”
Congratulations, Andy!
Neeraj Sakhrani and Co-Authors publish research article in Frontiers of Bioengineering and Biotechnology, section Tissue Engineering and Regenerative Medicine, titled “Toward Development of a Diabetic Synovium Culture Model.” Co-Authors include: Andy J. Lee, Lance A. Murphy, Hagar M. Kenawy, Christopher J. Visco, Gerard A. Atehsian, Roshan P. Shah, and Clark T. Hung.
Congratulations, everyone!
Abstract: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation and inflammation of synovium, the specialized connective tissue that envelops the diarthrodial joint. Type 2 diabetes mellitus (DM) is often found in OA patients, with nearly double the incidence of arthritis reported in patients with diabetes (52%) than those without it (27%). The correlation between OA and DM has been attributed to similar risk factors, namely increasing age and joint loading due to obesity. However, a potential causative link is not well understood due to comorbidities involved with treating diabetic patients, such as high infection rates and poor healing response caused by hyperglycemia and insulin resistance. The purpose of this study was to investigate the effect of hyperglycemic and insulin culture conditions on synovium properties. It was hypothesized that modeling hyperglycemia-induced insulin resistance in synovium would provide novel insights of OA pathogenesis in DM patients. To simulate DM in the synovial joint, healthy synovium was preconditioned in either euglycemic (EG) or hyperglycemic (HG) glucose concentrations with insulin in order to induce the biological response of the diseased phenotype. Synovium biochemical composition was evaluated to determine ECM remodeling under hyperglycemic culture conditions. Concurrent changes in AKT phosphorylation, a signaling pathway implicated in insulin resistance, were measured along with gene expression data for insulin receptors, glucose transporters, and specific glycolysis markers involved in glucose regulation. Since fluid shear stress arising during joint articulation is a relevant upstream stimulus for fibroblast-like synoviocytes (FLS), the predominant cell type in synovium, FLS mechanotransduction was evaluated via intracellular calcium ([Ca2+]i). Incidence and length of primary cilia, a critical effector of cell mechanosensing, were measured as potential mechanisms to support differences in [Ca2+]i responses. Hyperglycemic culture conditions decreased collagen and GAG content compared to EG groups, while insulin recovered ECM constituents. FLS mechanosensitivity was significantly greater in EG and insulin conditions compared to HG and non-insulin treated groups. Hyperglycemic treatment led to decreased incidence and length of primary cilia and decreased AKT phosphorylation, providing possible links to the mechanosensing response and suggesting a potential correlation between glycemic culture conditions, diabetic insulin resistance, and OA development.
Andy Garcia presented research at the 10th Annual Musculoskeletal Repair and Regeneration Symposium hosted by Albert Einstein College of Medicine and Montefiore Medical Center. His poster titled “Mimicking Benninghoff Arches in Cartilage Tissue Engineering for Improved Mechanics” was awarded the Young Investigator Award in Basic Science as the best research presentation in the predoctoral research category.
Congratulations, Andy!
Lianna Gangi publishes article in the Journal of Visualized Experiments titled “A Friction Testing-Bioreactor Device for Study of Synovial Joint Biomechanics, Mechanobiology, and Physical Regulation.”
Abstract: In primary osteoarthritis (OA), normal 'wear and tear' associated with aging inhibits the ability of cartilage to sustain its load-bearing and lubrication functions, fostering a deleterious physical environment. The frictional interactions of articular cartilage and synovium may influence joint homeostasis through tissue level wear and cellular mechanotransduction. To study these mechanical and mechanobiological processes, a device capable of replicating the motion of the joint is described. The friction testing device controls the delivery of reciprocal translating motion and normal load to two contacting biological counterfaces. This study adopts a synovium-on-cartilage configuration, and friction coefficient measurements are presented for tests performed in a phosphate-buffered saline (PBS) or synovial fluid (SF) bath. The testing was performed for a range of contact stresses, highlighting the lubricating properties of SF under high loads. This friction testing device can be used as a biomimetic bioreactor for studying the physical regulation of living joint tissues in response to applied physiologic loading associated with diarthrodial joint articulation.
Video coming soon! Below are behind the scenes photos of Lianna Gangi and co-author Courtney Petersen (Musculoskeletal Biomechanics Laboratory, Columbia University)
