Adele Changoor

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Dr. Changoor completed her undergraduate degree in Biological Engineering at the University of Guelph followed by a Master’s degree where she performed biomechanical studies to evaluate equine subchondral bone lesion repair. She then completed a PhD at École Polytechnique Montreal in the laboratory of Michael Buschmann where she developed novel methods of cartilage evaluation that were used to evaluate a cartilage repair device, which is now approved for clinical use.

During her postdoctoral fellowship she began to study electroarthrography, a non-invasive method for evaluating cartilage quality. She is now a staff scientist at the Lunenfeld-Tanenbaum Research Institute with a primary academic appointment in the Department of Surgery and does biomedical research in the areas of orthopaedics and arthritis.

Research Synopsis

The Changoor Laboratory is situated within the Grynpas Laboratory at the Lunenfeld-Tanenbaum Research Institute of Sinai Health System, which is on the 4th Floor of the TCP building at 25 Orde Street. The laboratory includes separate areas for biomechanics, histology, and image analysis, as well as general laboratory space and dedicated student offices.

Detection of Early Osteoarthritis

Degenerative joint diseases, such as Osteoarthritis (OA), are characterized by progressive deterioration of cartilage; the thin, connective tissue covering bones in articular joints that is uniquely adapted for load bearing. Arthritis can be painful and debilitating, and may eventually require surgery for symptom relief. While patients may benefit most from early intervention to prevent or slow arthritis progression1, cartilage deterioration occurring in early arthritis is often asymptomatic and cannot be identified by current clinical methodologies. There exists an unmet need for new diagnostic methods that are sensitive to the subtle cartilage changes associated with early arthritis and that are widely available to patients.

Cartilage produces electrical potentials during compression that correlate to cartilage load bearing properties2-3. This electromechanical phenomenon can be measured non-invasively using a method called electroarthrography (EAG)4-5. Contact electrodes are placed on skin external to an articulation and electrical fields recorded during joint loading. EAG can distinguish between normal and degraded cartilage6-7 and shows promise as a diagnostic method for detecting low grade cartilage degeneration and thereby identifying patients who may benefit from early interventions aimed at slowing arthritis progression. Developing EAG into a diagnostic device will involve pursuing experiments in explants of clinically relevant articular joints to create a database of EAG measurements and conventional cartilage properties, developing analytical methods to extract parameters related to cartilage quality, and translating EAG from a laboratory method into a practical clinical approach.

Improving Fresh Osteochondral Allograft Transplantation

The use of osteochondral allografts provides an effective treatment for large osteochondral lesions, especially in younger patients8. Clinical outcomes are encouraging, with studies reporting significant improvements in functional and quality of life scores9-10, as well as return to sport after one year in approximately 80% of patients11. Görtz12 et al. demonstrated that osteochondral allograft transplantation allowed 27 of 28 patients to avoid total knee arthroplasty. Success increases when chondrocyte viability in the donor allograft is maintained and upon reviewing the relevant basic science, De Caro8 et al. identified a need to develop a robust method for assessing chondrocyte viability immediately prior to transplantation. In addition, considering the rigorous loading environment experienced by articular joints in the lower extremities, an objective assessment of cartilage biomechanical properties in the donor allografts should be explored as a means to ensure that the most suitable tissue is being transplanted, which may then increase the likelihood of positive clinical outcomes for patients.

We aim to develop a robust protocol for assessing cartilage quality in allografts immediately prior to implantation. Our approach will include the use of a commercially available indentation probe that is capable of rapid and non-destructive measurement of cartilage electromechanical properties in the form of streaming potentials. Streaming potentials are produced during cartilage compression and directly reflect cartilage composition, structure and load bearing properties13-14. Sim15 et al. (2017) developed an electromechanical grade that strongly correlates to the ICRS visual grading system, which is a subjective score widely used during arthroscopy to qualitatively assess cartilage. These authors demonstrated that the new electromechanical grade, where cartilage streaming potentials are measured at multiple sites over articular surfaces, is more sensitive to early cartilage degeneration and is capable of identifying cartilage lesions that were not visible to the eye. We propose measuring cartilage streaming potentials in a series of benchtop experiment to follow cartilage quality in allografts from fresh through processing in preparation for transplantation, establish a typical range of cartilage quality in available allografts, and create a decision making tool to aid clinicians in selecting allograft tissue at the time of surgery.

[1] Lotz Arthritis Res Ther 2010;12:21. [2] Bonassar Acta Orthop Scand Suppl 1995;266:38. [3] Changoor J Biomech Eng 2011;133:061005. [4] Savard 2011 US Patent 2011/0034797 A1. [5] Préville Osteoarthr Cartil 2013;21:1731. [6] Changoor Trans Orthop Res Soc 2013;38:0170. [7] Changoor Osteoarthr Cartil 2013;21:s177. [8] De Caro Arthroscopy 2015;31:757. [9] LaPrade J Bone Joint Surg Am 2009;91:805. [10] Giorgini Injury 2013;44:s16. [11] Krych Am J Sports Med 2012;40:1053. [12] Görtz Clin Orthop Relat Res 2010;468:1269. [13] Frank J Biomech 1987;20(6):615. [14] Changoor J Biomech Eng 2011;133(6):061005. [15] Sim Ann Biomed Eng 2017;45(10):2410.

Selected Publications

Matsumoto Y, La Rose J, Lim M, Addisu HA, Law N, Mao X, Cong F, Mera P, Karsenty G, Goltzman D, Changoor A, Zhang L, Stajkowski M, Grynpas MD, Bergmann C, Rottapel R. Ubiquitin ligase RNF146 coordinates bone dynamics and energy metabolism. The Journal of Clinical Investigation. 2017; 127(7):2612-25.

Matsumoto Y, La Rose J, Kent OA, Lim M, Changoor A, Zhang L, Storozhuk Y, Mao X, Grynpas MD, Cong F, Rottapel R. RANKL coordinates multiple osteoclastogenic pathways by regulating expression of ubiquitin ligase RNF146. The Journal of Clinical Investigation. 2017; 127(4):1303-15.

Pilliar RM, Kandel RA, Grynpas MD, Theodoropoulos J, Hu Y, Allo B, Changoor A. Calcium polyphosphate particulates for bone void filler applications. Journal of Biomedical Materials Research. Part B, Applied Biomaterials. 2017; 105(4):874-84.

Méthot S, Changoor A, Tran-Khanh N, Hoemann CD, Stanish WD, Restrepo A, Shive MS, Buschmann MD. Osteochondral biopsy analysis demonstrates that BST-CarGel treatment improves structural and cellular characteristics of cartilage repair tissue compared with microfracture. Cartilage. 2015; 1947603515595837.

Hoemann CD, Tran-Khanh N, Lascau V, Chen G, Chevrier A, Matthieu C, Changoor A, Yaroshinsky A, McCormack R, Stanish WD, Buschmann MD. Chondroinduction is the main cartilage repair response to microfracture and microfracture with BST-CarGel as shown by histological scoring and a novel zonal collagen type (ZCT) scoring method of human clinical biopsies. The American Journal of Sports Medicine. 2015; 43(10):2469-80.

Changoor A, Nelea M, Méthot S, Tran-Khanh N, Chevrier A, Restrepo A, Shive MS, Hoemann CD, Buschmann MD. Structural characteristics of the collagen network in human normal, degraded and repair articular cartilages observed in polarized light and scanning electron microscopies. Osteoarthritis and Cartilage. 2011; 19(12):1458-68.

Changoor A, Coutu JP, Garon M, Quenneville E, Hurtig MB, Buschmann MD. Streaming potential-based arthroscopic device is sensitive to cartilage changes immediately post-impact in an equine cartilage injury model. Journal of Biomechanical Engineering. 2011; 133(6):061005.

Changoor A, Tran-Khanh N, Méthot S, Garon M, Hurtig MB, Shive MS, Buschmann MD. A polarized light microscopy method for accurate and reliable grading of collagen organization in cartilage repair. Osteoarthritis and Cartilage. 2011; 19(1): 126-35.

Changoor A, Fereydoonzad L, Yaroshinsky A, Buschmann MD. Effects of refrigeration and freezing on the electromechanical and biomechanical properties of articular cartilage. Journal of Biomechanical Engineering. 2010; 132(6):064502.

Changoor A, Hurtig MB, Runciman RJ, Quesnel AJ, Dickey JP, Lowerison M. Mapping of donor and recipient site properties for osteochondral graft reconstruction of subchondral cystic lesions in the equine stifle joint. Equine Veterinary Journal. 2006; 38(4): 330-6.

Changoor A, Runciman RJ, Hurtig MB. Osteochondral graft fixation using a bioresorbable bone cement. Journal of Biomechanics. 2006; 39(15):2887-92.