Localized Delivery of Ibuprofen via a Bilayer Delivery System (BiLDS) for Supraspinatus Tendon Healing in a Rat Model
The high prevalence of tendon re‐tear following rotator cuff repair motivates the development of new therapeutics to promote improved tendon healing. Controlled delivery of non‐steroidal anti‐inflammatory drugs (NSAIDs) to the repair site via an implanted scaffold is a promising option for modulating inflammation in the healing environment. Furthermore, biodegradable nanofibrous delivery systems offer an optimized architecture and surface area for cellular attachment, proliferation, and infiltration while releasing soluble factors to promote tendon regeneration.
To this end, we developed a bilayer delivery system (BiLDS) for localized and controlled release of ibuprofen to temporally mitigate inflammation and enhance tendon remodeling following surgical repair by promoting organized tissue formation. In vitro evaluation confirmed the delayed and sustained release of ibuprofen from Labrafil‐modified poly(lactic‐co‐glycolic) acid (PLGA) microspheres within sintered poly(ε‐caprolactone) (PCL) electrospun scaffolds. Biocompatibility of the BILDS was demonstrated with primary Achilles tendon cells in vitro. Implantation of the ibuprofen‐releasing BiLDS at the repair site in a rat rotator cuff injury and repair model led to decreased expression of pro‐inflammatory cytokine, TNF‐α, and increased anti‐inflammatory cytokine, TGF‐β1. The BiLDS remained intact for mechanical reinforcement and recovered the tendon structural properties by 8 weeks.
These results suggest the therapeutic potential of a novel biocompatible nanofibrous bilayer delivery system for localized and tailored delivery of ibuprofen to mitigate tendon inflammation and improve repair outcomes. Future studies are required to define the mechanical implications of an optimized BiLDS in a rat model beyond eight weeks or in a larger animal model.
Statement of Clinical Significance: This study investigates a biocompatible nanofibrous bilayer delivery system (BiLDS) for localized and controlled delivery of ibuprofen to mitigate inflammation following rotator cuff repair. Further evaluation is necessary to elucidate the prolonged beneficial effects of the system in a larger animal model.
Article Information: Brittany L. Taylor, Dong Hwa Kim, Julianne Huegel, Harina A. Raja, Sophie J. Burkholder, Stephanie N. Weiss, Courtney A. Nuss, Louis J. Soslowsky, Robert L. Mauck, Andrew F. Kuntz, Joseph Bernstein; Journal of Orthopaedic Research, 2020.