Reduction of arthrofibrosis utilizing a collagen membrane drug-eluting scaffold with celecoxib and subcutaneous injections with ketotifen.
Animals
Celecoxib
/ administration & dosage
Contracture
Cyclooxygenase 2 Inhibitors
/ administration & dosage
Disease Models, Animal
Drug Delivery Systems
Drug Evaluation, Preclinical
Female
Histamine H1 Antagonists
/ administration & dosage
Injections, Subcutaneous
Joint Diseases
/ drug therapy
Ketotifen
/ administration & dosage
Postoperative Complications
/ drug therapy
Rabbits
Random Allocation
acquired idiopathic stiffness
arthrofibrosis
celecoxib
ketotifen
total knee arthroplasty
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
09
12
2019
accepted:
29
02
2020
pubmed:
7
3
2020
medline:
2
2
2021
entrez:
6
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32134136
doi: 10.1002/jor.24647
pmc: PMC7483403
mid: NIHMS1576011
doi:
Substances chimiques
Cyclooxygenase 2 Inhibitors
0
Histamine H1 Antagonists
0
Celecoxib
JCX84Q7J1L
Ketotifen
X49220T18G
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2474-2483Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR072597
Pays : United States
Informations de copyright
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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