A new study published in Science Advances showcases a promising technique that leverages nanoparticles to deliver drugs precisely to surgically repaired tendons, reducing scar tissue formation and enhancing mechanical function. This innovative approach demonstrates the potential for efficient drug delivery at the cellular level, offering new possibilities for treating various injuries.
Whether it’s a career-ending Achilles injury in a professional athlete like Aaron Rodgers or a common workplace mishap, tendon injuries are prevalent and can have a lasting impact. With around 300,000 surgeries performed annually for tendon injuries, there is a significant need for effective treatments to address the resulting physical limitations and work disruptions.
Typically, traumatic tendon injuries are repaired surgically using sutures, but the healing process is often complicated by excessive scar tissue formation, which hinders the flexibility and function of the tendon.
Researchers from the University of Rochester and University of Oregon collaborated to explore innovative methods for delivering therapies that can promote healing by reducing scar tissue and enhancing recovery.
According to Alayna Loiselle, PhD, an associate professor at the University of Rochester’s Center for Musculoskeletal Research, current drug treatments for tendon healing are limited in their effectiveness, with oral or injected medications often failing to target the injured tendon efficiently. Local administration of drugs directly to the tendon has drawbacks, including potential tissue damage and inadequate control over drug concentrations at the injury site.
Emmanuela Adjei-Sowah, a Biomedical Engineering PhD student at the University of Rochester, highlighted the shift from relying solely on sutures to incorporating therapeutic interventions. By developing a nanoparticle delivery system in collaboration with researchers like Loiselle and Danielle S.W. Benoit, the team aims to enhance healing in tendon injuries through advanced drug delivery methods.
The researchers faced the challenge of identifying substances that could aid in tendon healing.
Uncovering a New Therapeutic Approach Through Molecular Insights
“Our understanding of the cellular and molecular processes driving scar-mediated tendon healing is still evolving,” explained Loiselle. “Through our research, we discovered high levels of Acp5 gene expression at the injury site, indicating the presence of Tartrate Resistant Acid Phosphatase (TRAP) protein, which is associated with bone repair. This insight paved the way for targeted drug delivery using a peptide that binds to TRAP at the healing tendon site.”
Prior to testing therapeutic agents, the team conducted dose and timing studies using a mouse model to determine the optimal window for targeting the healing tendon with their drug delivery system after a tendon injury and surgical repair.
Danielle S.W. Benoit, a professor at the University of Oregon, emphasized the importance of defining the treatment window to develop an effective drug delivery system that promotes regenerative healing and minimizes side effects typically associated with high drug doses.
Niclosamide, chosen as the therapeutic agent, inhibits S100a4 protein, identified by Loiselle’s lab as a contributor to scar tissue formation. Using the nanoparticle delivery system, the research team was able to precisely target the injured tendon and inhibit S100a4 expression, leading to improved mechanical function and range of motion in the healed tendon.
Comparatively, systemic delivery of Niclosamide showed limited effectiveness in reducing S100a4 levels in the healing tendon, highlighting the advantages of the nanoparticle-based drug delivery method.
This targeted approach not only enhanced tendon healing but also improved functional recovery and mechanical strength across different time points. Remarkably, these positive effects were sustained with just a single treatment.
The researchers plan to explore the broader applicability of this system for various tendon injuries and conditions, as well as other tissue injuries that involve scar formation.
“The versatility of this system lies in its capacity to carry different drugs targeting diverse molecular pathways,” added Adjei-Sowah.
