Functional recovery after peripheral nerve injury via sustained growth factor delivery from mineral-coated microparticles
Daniel J. Hellenbrand1
Clayton L. Haldeman2
Jae-Sung Lee3
Angela G. Gableman2
Elena K. Dai2
Stephen D. Ortmann2
Jerrod C. Gotchy2
Kierra K. Miller2
Adrianna M. Doucas2
Nicole C. Nowak2
William L. Murphy3
Amgad S. Hanna2
1.Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA;Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA2.Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA3.Department of Biomedical Engineering, University of Wisconsin, Madison, WI, USA;Department of Orthopedics and Rehabilitation University of Wisconsin Madison, WI, USA
摘要：The gold standard for treating peripheral nerve injuries that have large nerve gaps where the nerves cannot be directly sutured back together because it creates tension on the nerve, is to incorporate an autologous nerve graft. However, even with the incorporation of a nerve graft, generally patients only regain a small portion of function in limbs affected by the injury. Although, there has been some promising results using growth factors to induce more axon growth through the nerve graft, many of these previous therapies are limited in their ability to release growth factors in a sustained manner and tailor them to a desired time frame. The ideal drug delivery platform would deliver growth factors at therapeutic levels for enough time to grow axons the entire length of the nerve graft. We hypothesized that mineral coated microparticles (MCMs) would bind, stabilize and release biologically active glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in a sustained manner. Therefore, the objective of this study was to test the ability of MCMs releasing growth factors at the distal end of a 10 mm sciatic nerve graft, to induce axon growth through the nerve graft and restore hind limb function. After sciatic nerve grafting in Lewis rats, the hind limb function was tested weekly by measuring the angle of the ankle at toe lift-off while walking down a track. Twelve weeks after grafting, the grafts were harvested and myelinated axons were analyzed proximal to the graft, in the center of the graft, and distal to the graft. Under physiological conditions in vitro, the MCMs delivered a burst release of NGF and GDNF for 3 days followed by a sustained release for at least 22 days. In vivo, MCMs releasing NGF and GDNF at the distal end of sciatic nerve grafts resulted in significantly more myelinated axons extending distal to the graft when compared to rats that received nerve grafts without growth factor treatment. The rats with nerve grafts incorporated with MCMs releasing NGF and GDNF also showed significant improvement in hind limb function starting at 7 weeks postoperatively and continuing through 12 weeks postoperatively when compared to rats that received nerve grafts without growth factor treatment. In conclusion, MCMs released biologically active NGF and GDNF in a sustained manner, which significantly enhanced axon growth resulting in a significant improvement of hind limb function in rats. The animal experiments were approved by University of Wisconsin-Madison Animal Care and Use Committee (ACUC, protocol# M5958) on January 3, 2018.
机标关键词：
分类号：R456(治疗学)R364(病理学)R605(外科治疗学)
论文发表日期：2021-05-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 871-877 )
英文信息