Hypovascularity of dense connective tissue limits its healing potential after injury. Because of this, surgically repaired tendons and other dense connective tissues heal slowly and often don’t retain the structural and mechanical integrity of healthy tissues. For example, rotator cuff repairs have surgical repair failure rates as high at 95%. Accelerating and/or improving the natural healing process by promoting increased tissue vascularity would enhance the quality of life for people affected by connective tissue injuries. Addressing this clinical challenge has the potential to significantly improve the overall quality of life of millions of people. In the US alone, more than 16 million tendon injuries are reported each year.
Angiogenic promoters, growth factors, and even viral gene transfer methods have been delivered to injured tendons to promote vascularity and healing capacity. Results from these studies have produced inconsistent effects of locally delivering specific growth factors to stimulate tendon healing. There are also cost and manufacturing concerns associated with growth factors and viral gene transfer. Combined, these studies suggest that angiogenic factors and delivery methods needs to be optimized to promote healing.
Researchers from the Departments of Orthopedics, Exercise and Sport Science, and Biomedical Engineering at the University of North Carolina – Chapel Hill have developed a novel approach to increase the healing potential of injured tendons through localized delivery of the angiogenic promoter, deferoxamine (DFO). DFO is an FDA approved iron chelator used to treat diseases of excess iron. Treatment with DFO leads to accumulation of hypoxia-inducible factor 1 a (HIF-1a) which is a global transcription factor that turns on genes responsible for new blood vessel formation. Localized delivery is accomplished through a novel delivery system that involves crosslinking and immobilizing DFO to a sheet of gelatin matrix. This DFO loaded gelatin matrix can be applied by a surgeon directly to specific areas of an injured tendon to coordinately activate and enhance the expression of angiogenic genes to promote tendon healing. Enhanced healing of the Achilles tendon in an animal model has been demonstrated with local delivery of DFO through the gelatin matrix.
- Utilizes an FDA approved drug, providing an accelerated path to use.
- The drug coordinately activates and enhances the expression of multiple genes that promote tendon healing.
- Cost effective and easy to manufacture.
- Orthopedic surgeon can spatially direct the drug to promote healing.
Clinical applications could include repair of Achilles tendon, flexor tendons and rotator cuffs.