Journal article
Blebbistatin-Loaded Poly(d,l-lactide-co-glycolide) Particles For Treating Arthrofibrosis
ACS biomaterials science & engineering, Vol.2(7), pp.1097-1107
07/11/2016
DOI: 10.1021/acsbiomaterials.6b00082
PMID: 33445238
Abstract
Joint immobility is a debilitating complication of articular trauma that is characterized by thickening and stiffening of the joint capsule and the formation of fibrotic lesions inside joints. Capsule release surgery can temporarily restore mobility, but contraction often recurs due to the contractile activities of fibroblasts, which exert tension on the capsule ECM via nonmuscle myosin II. Based on these findings we hypothesized that blebbistatin, a drug that reversibly inhibits the activity of this protein, would relax ECM tension imposed by fibroblasts and reduce fibrosis. In this study, we characterized the effectiveness of blebbistatin as an anticontractile treatment. Given that sustained suppression of contractile activity may be required to achieve capsule release and reduce fibrosis, we compared the effects on fibroblast-mediated collagen ECM displacement of blebbistatin-loaded poly(lactide-co-gylcolide) (PLGA) particles versus bolus blebbistatin dosing. Time-lapse imaging of fluorescent microspheres embedded in collagen gels confirmed that PLGA/blebbistatin inhibited force generation and reduced both gel displacement and rate of displacement. In addition, collagen production at 10 days was significantly reduced. Taken together, these data indicate that blebbistatin-loaded PLGA particles can be used to inhibit fibroblast force-generation and reduce collagen production and lay the foundation for optimization of drug delivery technology for treating arthrofibrosis.
Details
- Title: Subtitle
- Blebbistatin-Loaded Poly(d,l-lactide-co-glycolide) Particles For Treating Arthrofibrosis
- Creators
- K Atluri - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, 115 South Grand Avenue, Iowa City, Iowa 52242, United StatesA.M De Jesus - Department of Biomedical Engineering, University of Iowa College of Engineering, 1402 Seamans Center, Iowa City, Iowa 52242, United StatesS Chinnathambi - Department of Biomedical Engineering, University of Iowa College of Engineering, 1402 Seamans Center, Iowa City, Iowa 52242, United StatesM.J Brouillette - Department of Orthopaedics and Rehabilitation, University of Iowa Roy J and Lucille A Carver College of Medicine, 25 South Grand Avenue, Iowa City, Iowa 52242, United StatesJ.A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa Roy J and Lucille A Carver College of Medicine, 25 South Grand Avenue, Iowa City, Iowa 52242, United StatesA.K Salem - Division of Pharmaceutics and Translational Therapeutics, University of Iowa College of Pharmacy, 115 South Grand Avenue, Iowa City, Iowa 52242, United States, Department of Biomedical Engineering, University of Iowa College of Engineering, 1402 Seamans Center, Iowa City, Iowa 52242, United StatesE.A Sander - Department of Biomedical Engineering, University of Iowa College of Engineering, 1402 Seamans Center, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- ACS biomaterials science & engineering, Vol.2(7), pp.1097-1107
- DOI
- 10.1021/acsbiomaterials.6b00082
- PMID
- 33445238
- NLM abbreviation
- ACS Biomater Sci Eng
- ISSN
- 2373-9878
- eISSN
- 2373-9878
- Grant note
- DOI: 10.13039/100000182, name: Medical Research and Materiel Command, U.S. Army Medical Department, award: W81XWH-14-0327; DOI: 10.13039/100000147, name: Division of Civil, Mechanical and Manufacturing Innovation, award: CMMI 1452728; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust, award: 14-4384
- Language
- English
- Date published
- 07/11/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984040333602771
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