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Functional recovery after peripheral nerve injury via sustained growth factor delivery from mineral-coated microparticles

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Neural Regeneration Research 2021年第5期16卷 871-877页

作者： Daniel J.Hellenbrand clayton l.haldeman Jae-Sung lee Angela G.Gableman Elena K.Dai Stephen D.Ortmann Jerrod CGotchy Kierra K.Miller Adrianna M.Doucas Nicole C.Nowak William l.Murphy Amgad S.Hanna Department of Neurological Surgery University of WisconsinMadisonWIUSA Department of Biomedical Engineering University of WisconsinMadisonWIUSA Department of Orthopedics and Rehabilitation University of Wisconsin Madison WIUSA

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 ***,even with the incorporation of a nerve graft,generally patients only regain a small portion of function in limbs affected by the ***,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 *** ideal drug delivery platform would deliver growth factors at therapeutic levels for enough time to grow axons the entire length of the nerve *** 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 ***,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 *** 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 *** 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 *** 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 *** 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 *** rats with nerve grafts incorporated with MCMs releasing NGF and G

关键词： autografts axon growth drug delivery glial cell-derived neurotrophic factor growth factors mineral coatings nerve grafting nerve growth factor

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