Sustained release of neurotrophin‐3 via calcium phosphate‐coated sutures promotes axonal regeneration after spinal cord injury

• DOI: 10.1002/jnr.23730
• Publication Date: 2016-03-26T14:04:26Z
• Authors: Amgad Hanna; Daniel L. Thompson; Daniel J. Hellenb...; Jae‐Sung Lee; Casey J. Madura; Meredith G. Wesley; Natalie J. Dillon; Tapan Sharma; Connor J. Enright; William L. Murphy
• Keywords: Calcium Phosphates; 0301 basic medicine; Cholera Toxin; Sutures; Tissue Scaffolds; Graft Survival; Recovery of Function; Axons; 12. Responsible consumption; Nerve Regeneration; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Neurotrophin 3; Neurofilament Proteins; Delayed-Action Preparations; Animals; Female; Spinal Cord Injuries

Because of the dynamics of spinal cord injury (SCI), the optimal treatment will almost certainly be a combination approach to control the environment and promote axonal growth. This study uses peripheral nerve grafts (PNGs) as scaffolds for axonal growth while delivering neurotrophin‐3 (NT‐3) via calcium phosphate (CaP) coatings on surgical sutures. CaP coating was grown on sutures, and NT‐3 binding and release were characterized in vitro. Then, the NT‐3‐loaded sutures were tested in a complete SCI model. Rats were analyzed for functional improvement and axonal growth into the grafts. The CaP‐coated sutures exhibited a burst release of NT‐3, followed by a sustained release for at least 20 days. Functionally, the rats with PNGs + NT‐3‐loaded sutures and the rats treated with PNGs scored significantly higher than controls on day 56 postoperatively. However, functional scores in rats treated with PNGs + NT‐3‐loaded suture were not significantly different from those of rats treated with PNGs alone. Cholera toxin subunit B (CTB) labeling rostral to the graft was not observed in any controls, but CTB labeling rostral to the graft was observed in almost all rats that had had a PNG. Neurofilament labeling on transverse sections of the graft revealed that the rats treated with the NT‐3‐loaded sutures had significantly more axons per graft than rats treated with an NT‐3 injection and rats without NT‐3. These data demonstrate that PNGs serve as scaffolds for axonal growth after SCI and that CaP‐coated sutures can efficiently release NT‐3 to increase axonal regeneration. © 2016 Wiley Periodicals, Inc.