Novel Thermosensitive Heparin-poloxamer Hydrogel Bridge NGF to Treat Peripheral Nerve Injury in Diabetics Rats
LI Rui1,2, LI Duo-hui2, QUAN Da-ping1, XIAO Jian2*
1. School of Chemistry, Laboratory of Polymer Chemistry and Physics, Sun Yat-sen University, Guangzhou 510127, China;
2. College of Pharmacy of Wenzhou Medical University, Zhejiang Provincial Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou 325035, China
OBJECTIVE To investigate the effects of NGF-HP thermosensitive hydrogel on facilitating structural and functional regeneration in diabetic rats with sciatic nerve crush injury. METHODS Eight-week-old male SD rats (200-220 g) were intraperitoneally injected wither steptozocin(STZ) to induce diabetes. After success of model establishment, the sciatic nerve of the diabetes rats were made crushed through two vascular clips force. Muscle and skin were then closed with 5-0 stitches. Following surgery, the rats were randomly divided into three groups: PNI-diabetics group, free NGF group and NGF-HP hygrogel group. Each group received corresponding therapeutic drugs through a microsyringe. The motor recovery in all tested rats was assessed using Basso-Beattie-Bresnahan (BBB) locomotion scale and inclined plane test at indicated time points. After 30 d, rats were sacrificed, the crushed nerve and corresponding gastrocnemius muscle were harvested and the pathology index was assessed.The expressions of structural and functional proteins were detected through immunoblotting.The improvement of axon and myelination regeneration were evaluated via immunofluorescence, Masson′s trichrom stain and transmission electron microscope. RESULTS NGF-HP not only had a good affinity for a certain amounts of nerve growth factor (NGF), but also controlled its release in a steady fashion in vitro. In vivo, compared with administration of direct free NGF, single injection of NGF-HP hydrogel was more effective at upregulating the expression of nerve associated structural and functional proteins, enhancing axonal regeneration and remyelination, as well as improving motor function recovery. CONCLUSION This new type of hydrogel loaded with NGF shows striking effects on functional and morphometric recovery on peripheral nerve injury (PNI) following diabetes,which may provide a theoretical basis strategies for remedying PNI-diabetes in clinical populations.
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