@article{c1f4eb8c11d54a05b3930106c9701576,
title = "Reduction of arthrofibrosis utilizing a collagen membrane drug-eluting scaffold with celecoxib and subcutaneous injections with ketotifen",
abstract = "The dense formation of abnormal scar tissue after total knee arthroplasty results in arthrofibrosis, an unfortunate sequela of inflammation. The purpose of this study was to use a validated rabbit model to assess the effects on surgically-induced knee joint contractures of two combined pharmacological interventions: celecoxib (CXB) loaded on an implanted collagen membrane, and subcutaneously (SQ) injected ketotifen. Thirty rabbits were randomly divided into five groups. The first group received no intervention after the index surgery. The remaining four groups underwent intra-articular implantation of collagen membranes loaded with or without CXB at the time of the index surgery; two of which were also treated with SQ ketotifen. Biomechanical joint contracture data were collected at 8, 10, 16, and 24 weeks. At the time of necropsy (24 weeks), posterior capsule tissue was collected for messenger RNA and histopathologic analyses. At 24 weeks, there was a statistically significant increase in passive extension among rabbits in all groups treated with CXB and/or ketotifen compared to those in the contracture control group. There was a statistically significant decrease in COL3A1, COL6A1, and ACTA2 gene expression in the treatment groups compared to the contracture control group (P <.001). Histopathologic data also demonstrated a trend towards decreased fibrous tissue density in the CXB membrane group compared to the vehicle membrane group. The present data suggest that intra-articular placement of a treated collagen membrane blunts the severity of contracture development in a rabbit model of arthrofibrosis, and that ketotifen and CXB may independently contribute to the prevention of arthrofibrosis. Statement of clinical significance: Current literature has demonstrated that arthrofibrosis may affect up to 5% of primary total knee arthroplasty patients. For that reason, novel pharmacologic prophylaxis and treatment modalities are critical to mitigating reoperations and revisions while improving the quality of life for patients with this debilitating condition.",
keywords = "acquired idiopathic stiffness, arthrofibrosis, celecoxib, ketotifen, total knee arthroplasty",
author = "Limberg, {Afton K.} and Tibbo, {Meagan E.} and Salib, {Christopher G.} and McLaury, {Alex R.} and Turner, {Travis W.} and Berry, {Charlotte E.} and Jay, {Anthony G.} and Carter, {Jodi M.} and Brad Bolon and Berry, {Daniel J.} and Morrey, {Mark E.} and Joaquin Sanchez-Sotelo and {van Wijnen}, {Andre J.} and Abdel, {Matthew P.}",
note = "Funding Information: The authors would like to acknowledge lab members of the Abdel and van Wijnen laboratories for their critical review of this work and their insightful discussions and/or assistance with reagents and procedures. The research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) under Award Number AR072597-01A1 and the Anna-Maria and Stephen Kellen Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would like to thank the entire Mayo Clinic Department of Comparative Medicine for their expertise in animal care, and Kristin C. Mara, M.S., and Dirk R. Larson, M.S. in the Mayo Clinic Department of Medical Biostatistics and Informatics for their expertise in data analysis throughout the duration of this study. We would also like to thank the Pathology Research Core at the Mayo Clinic for their work on the immunohistochemistry. Funding Information: The authors would like to acknowledge lab members of the Abdel and van Wijnen laboratories for their critical review of this work and their insightful discussions and/or assistance with reagents and procedures. The research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) under Award Number AR072597‐01A1 and the Anna‐Maria and Stephen Kellen Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. We would like to thank the entire Mayo Clinic Department of Comparative Medicine for their expertise in animal care, and Kristin C. Mara, M.S., and Dirk R. Larson, M.S. in the Mayo Clinic Department of Medical Biostatistics and Informatics for their expertise in data analysis throughout the duration of this study. We would also like to thank the Pathology Research Core at the Mayo Clinic for their work on the immunohistochemistry. Publisher Copyright: {\textcopyright} 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.",
year = "2020",
month = nov,
day = "1",
doi = "10.1002/jor.24647",
language = "English (US)",
volume = "38",
pages = "2474--2483",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "11",
}