The impact of PTH on the healing of the tendon-to-bone insertion site - A rodent model

• Applicant: Dr. Martin Husen
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: from 2021 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 466023693

Injuries to the tendon-to-bone interface complex such as Achilles tendon (AT) injuries are frequent and associated with considerable morbidity, loss of ability to work, and diminished quality of life. AT injuries have a lifetime cumulative incidence of more than 50% in physically active populations (e.g., runners). Despite the constant improvement of surgical techniques and suture materials, the rate of complications exceeds 10% after Achilles tendon reconstruction. Fast and sufficient tendon-to-bone healing is a key factor in the treatment of injured patients. Surgical reconstruction depends on the fixation of two tissues (bone and tendon) with vastly different morphological and biomechanical properties, and relies on new bone formation to anchor the tendon in the bone tunnel during early recovery.The proposed project aims at enhancing the osseointegration of the tendon by locally administering parathyroid hormone binding peptide (PTH) to the reconstruction site. While the systemic application of PTH in patients suffering from osteoporosis poses an accepted, approved and widely used treatment, its treatment duration is limited to 2 years because of side effects. Following our previous studies, we will test the hypothesis whether the local application of PTH-binding peptide leads to an increased local concentration of endogenous PTH within the tendon-to-bone insertion site upon injury repair. Currently, there is no suture material available, which enables the local binding of PTH. Therefore, we developed a bioactivated, surgical suture material which contains covalently bound PTH-binding peptide. The peptide as well as the procedure for covalent binding were established in previous studies. The intermittent presence of PTH at the site of injury has an anabolic effect on bone metabolism. The use of PTH-binding peptide will enable us to take advantage of the effect of endogenous PTH. The suture material enriched with PTH-binding peptide will be applied in an Achilles tendon injury rat model. The following analyses of the tendon-to-bone interface will include biomechanics studies, histological and genetic analysis, as well as protein analysis. Imaging will be performed using micro-CT. A positive effect of the use of bio activated suture materials containing PTH-binding peptide during the healing of Achilles tendon injuries could pave the way for clinical applications.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Daniel Saris, Ph.D.