TY - JOUR
T1 - A Drug Eluting Scaffold for the Treatment of Arthrofibrosis
AU - Trousdale, William H.
AU - Salib, Christopher G.
AU - Reina, Nicolas
AU - Lewallen, Eric A.
AU - Viste, Anthony
AU - Berry, Daniel J.
AU - Morrey, Mark E.
AU - Sanchez-Sotelo, Joaquin
AU - Van Wijnen, Andre J.
AU - Abdel, Matthew P.
N1 - Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc., publishers 2018.
PY - 2018/9
Y1 - 2018/9
N2 - Introduction: The inflammatory cascade and production of prostaglandins may play a role in the pathogenesis of arthrofibrosis, a debilitating condition after joint replacement and other orthopedic procedures. Cyclooxygenase 2 (COX-2) inhibitors may mitigate the inflammatory response and formation of arthrofibrosis, but oral delivery is associated with risk of systemic side effects in many patients. The nonsteroidal anti-inflammatory drug, celecoxib, may have therapeutic benefits for arthrofibrosis, but current methods for its local delivery (e.g., biologically derived microspheres) are not translatable to immediate clinical use. Therefore, we investigated the use of a drug scaffold for sustainable intra-articular delivery of therapeutic doses of celecoxib. Materials and Methods: Celecoxib was eluted from clinically approved biodegradable collagen membranes over 7 days as measured by UV spectroscopy and high-performance liquid chromatography/mass spectroscopy. Eluted concentrations of celecoxib were examined for toxicity (live/dead staining) and profibrotic gene expression (real-time-quantitative polymerase chain reaction) in rabbit knee capsular fibroblasts in vitro. Results: Sustained concentrations of celecoxib eluted from the membrane over 7 days from both a wet and dry scaffold, with a burst release (30-45%) of celecoxib in the first 2 h. Rabbit cells treated with eluted concentrations experienced a toxic response to the burst release doses, and inhibitory effects on profibrotic genes were seen in response to the sustained doses eluted from the scaffold. Conclusions: This study characterized the novel use of collagen scaffolds for intra-articular drug delivery to treat arthrofibrosis. Scaffolds exhibit celecoxib release through an initial burst release followed by sustained release of antifibrotic doses over 7 days. Thus, collagen scaffolds are promising for clinician-directed treatment of arthrofibrosis.
AB - Introduction: The inflammatory cascade and production of prostaglandins may play a role in the pathogenesis of arthrofibrosis, a debilitating condition after joint replacement and other orthopedic procedures. Cyclooxygenase 2 (COX-2) inhibitors may mitigate the inflammatory response and formation of arthrofibrosis, but oral delivery is associated with risk of systemic side effects in many patients. The nonsteroidal anti-inflammatory drug, celecoxib, may have therapeutic benefits for arthrofibrosis, but current methods for its local delivery (e.g., biologically derived microspheres) are not translatable to immediate clinical use. Therefore, we investigated the use of a drug scaffold for sustainable intra-articular delivery of therapeutic doses of celecoxib. Materials and Methods: Celecoxib was eluted from clinically approved biodegradable collagen membranes over 7 days as measured by UV spectroscopy and high-performance liquid chromatography/mass spectroscopy. Eluted concentrations of celecoxib were examined for toxicity (live/dead staining) and profibrotic gene expression (real-time-quantitative polymerase chain reaction) in rabbit knee capsular fibroblasts in vitro. Results: Sustained concentrations of celecoxib eluted from the membrane over 7 days from both a wet and dry scaffold, with a burst release (30-45%) of celecoxib in the first 2 h. Rabbit cells treated with eluted concentrations experienced a toxic response to the burst release doses, and inhibitory effects on profibrotic genes were seen in response to the sustained doses eluted from the scaffold. Conclusions: This study characterized the novel use of collagen scaffolds for intra-articular drug delivery to treat arthrofibrosis. Scaffolds exhibit celecoxib release through an initial burst release followed by sustained release of antifibrotic doses over 7 days. Thus, collagen scaffolds are promising for clinician-directed treatment of arthrofibrosis.
KW - arthrofibrosis
KW - collagen
KW - joint replacement
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U2 - 10.1089/ten.tec.2018.0136
DO - 10.1089/ten.tec.2018.0136
M3 - Article
C2 - 30101668
AN - SCOPUS:85053663300
SN - 1937-3384
VL - 24
SP - 514
EP - 523
JO - Tissue Engineering - Part C: Methods
JF - Tissue Engineering - Part C: Methods
IS - 9
ER -