Articular cartilage damage is one of the most expensive of the debilitating non-life threatening diseases in the US (Jackson et al., 2001c). Non-arthroplasty treatments for cartilage defects-such as lavage, debridment, and microfracture-appear to provide short term pain relief and the long-term outcome of these procedures remains unclear (Gilbert 1998). The current6 standard-of-care treatment for focal cartilage defects is the transplantation of autogenous osteochondral plugs from non- weight bearing areas; an approach which has had reasonable short-term success (Sanders et al., Fitzpatrick and Morgan, 1998; Horas et al., 2000), but also faces many unresolved technical challenges including matching donor and host site profiles and tissue material properties. The objective of this study is to explore the feasibility of stabilizing focal cartilage defects by inserting a non-degradable synthetic plug into the defect. Our hypothesis is that the structural integrity of a permanent plug and its surrounding tissue can be maintained by insertion of a plug that is more compliant compared with the surrounding cartilage. The plugs intended for use in this study are degradable synthetic plugs made of poly(vinyl alcohol) PVA, the properties of which can be altered through compositional and structural changes. The first requirement of this study is to choose two hydrogel plug groups with different instantaneous mechanical property profiles. The second phase is to insert both plug types into a distal femoral rabbit osteochondral defect model. Our hypotheses will be tested by quantifying the stability of plug fixation to the surrounding bone, assessing how adequately the plug shares load with the surrounding and opposing cartilage, and how effectively it transfers load to the underlying bone.
The specific aims can be summarized as follows:
Specific Aim 1 : Specify two groups of hydrogel plugs so that their structure and composition results in; a) material properties that are within the range or published values for rabbit temporal condyle articular cartilage, and b) material properties with a 50% increase in compliance compared to rabbit femoral condyle articular cartilage.
Specific Aim 2 : Quantify the structural, compositional, and mechanical incorporation of hydrogel plugs into rabbit femoral condyle focal osteochondral defects over time periods extending to 12 months, as a function of time and of hydrogel material properties. The goal of our approach is to stabilize the cascade of events that accompanies the presence of focal cartilage defects, a cascade that left untreated usually results in osteoarthritis. It is our contention that drilling through subchondral bone and inserting a hydrogel plug with specifically chosen material properties will provide an acceptable pain free, functional clinical outcome.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZAR1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Hospital for Special Surgery
New York
United States
Zip Code
Qu, Dovina; Subramony, Siddarth D; Boskey, Adele L et al. (2017) Compositional mapping of the mature anterior cruciate ligament-to-bone insertion. J Orthop Res 35:2513-2523
Ishack, Stephanie; Mediero, Aranzazu; Wilder, Tuere et al. (2017) Bone regeneration in critical bone defects using three-dimensionally printed ?-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2. J Biomed Mater Res B Appl Biomater 105:366-375
Yang, Haisheng; Albiol, Laia; Chan, Wing-Lee et al. (2017) Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging. J Biomech 65:145-153
Foster, B L; Kuss, P; Yadav, M C et al. (2017) Conditional Alpl Ablation Phenocopies Dental Defects of Hypophosphatasia. J Dent Res 96:81-91
Mediero, Aránzazu; Wilder, Tuere; Ramkhelawon, Bhama et al. (2016) Netrin-1 and its receptor Unc5b are novel targets for the treatment of inflammatory arthritis. FASEB J 30:3835-3844
Mediero, Aránzazu; Ramkhelawon, Bhama; Wilder, Tuere et al. (2016) Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis. Ann Rheum Dis 75:1706-13
Mediero, Aránzazu; Wilder, Tuere; Reddy, Vishnu S R et al. (2016) Ticagrelor regulates osteoblast and osteoclast function and promotes bone formation in vivo via an adenosine-dependent mechanism. FASEB J 30:3887-3900
Masci, Marco; Wang, Min; Imbert, Laurianne et al. (2016) Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta. Bone 87:120-9
Holyoak, Derek T; Tian, Ye F; van der Meulen, Marjolein C H et al. (2016) Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment. Ann Biomed Eng 44:2062-75
Morgan, Timothy G; Bostrom, Mathias P G; van der Meulen, Marjolein C H (2015) Tissue-level remodeling simulations of cancellous bone capture effects of in vivo loading in a rabbit model. J Biomech 48:875-82

Showing the most recent 10 out of 195 publications