Collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor promote neurological and locomotor function recovery in rats after traumatic brain injury

doi:10.3969/j.issn.2095-4344.2316

Chinese Journal of Tissue Engineering Research ›› 2020, Vol. 24 ›› Issue (34): 5538-5544.doi: 10.3969/j.issn.2095-4344.2316

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Collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor promote neurological and locomotor function recovery in rats after traumatic brain injury

Zhang Jian^{1, 2}, Chen Miao³, Li Weixin¹, Ye Yichao^{1, 2}, Xu Huiyou^1,², Ma Ke^1,², Chen Xuyi², Sun Hongtao², Zhang Sai²

¹Logistics University of People’s Armed Police Force; ²Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People’s Armed Police Force, Tianjin Key Laboratory of Neurotruama Repair,; ³The Fourth Clinical Medical College of Xinjiang Medical University

Received:2019-12-03 Revised:2019-12-10 Accepted:2020-01-18 Online:2020-11-08 Published:2020-09-11
Contact: Sun Hongtao, Chief physician, Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotruama Repair, Tianjin 300171, China
About author:Zhang Jian, Master candidate, Logistics University of People's Armed Police Force, Tianjin 300300, China; Institute of Neurotrauma Repair, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin Key Laboratory of Neurotruama Repair, Tianjin 300171, China Chen Miao, Master candidate, The Fourth Clinical Medical College of Xinjiang Medical University, Urumqi 830002, Xinjiang Uygur Autonomous Region, China
Supported by:
the National Natural Science Foundation of China, Nos. 11672332, 11102235; the National Natural Science Foundation of China, No. 11932013; the National Key Research and Development Plan of China, No. 2016YFC1101500; the Natural Science Foundation of Tianjin, No. 15JCYBJC28600; the Natural Science Foundation of Tianjin, No. 17JCDJC5400; Tianjin Science and Technology Support Key Project, No. 17YFZCSY00620; Science and Technology Military-Civilian Integration Project of Tianjin, No.18ZXJMTG00260

Abstract

Abstract:

BACKGROUND: The porous scaffold fabricated with collagen and heparin sulfate can effectively immobilize neurotrophic factor and greatly improve neurological and locomotor function recovery.

OBJECTIVE: To investigate the effect of collagen/heparan sulfate scaffold loaded with brain-derived neurotrophic factor in the treatment of traumatic brain injury (TBI).

METHODS: Collagen scaffolds, collagen/heparan sulfate scaffolds and collagen/heparan sulfate scaffolds loaded with brain-derived neurotrophic factor were prepared. The porosity, water absorption, compression modulus and compression stress of collagen scaffolds and collagen/heparan sulfate scaffolds were measured. The in vitro sustained-release performance of collagen/heparan sulfate scaffolds loaded with brain-derived neurotrophic factor was measured. The cytotoxicity and cytocompatibility of collagen/heparin sulfate scaffolds and collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor were detected. Forty-eight Sprague-Dawley rats were randomly assigned to undergo corresponding interventions: opening bone window followed by suture (control group), induction of craniocerebral trauma (model group), induction of craniocerebral trauma + implantation of collagen/heparin sulfate scaffolds (scaffold group), and induction of craniocerebral trauma + implantation of collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor (brain-derived neurotrophic factor group). After surgery, modified neurological severity scoring and Morris water maze test were performed to evaluate the recovery of neurological and locomotor function. Rat cerebral morphology was performed. This study was approved by the Animal Ethics Committee of Characteristic Medical Center of Chinese People's Armed Police Force, China.

RESULTS AND CONCLUSION: (1) The porosity, compression modulus and compression stress of the collagen/heparin sulfate scaffold were significantly higher than those of the collagen scaffold (P < 0.05), and the water absorption rate of the collagen/heparin sulfate scaffold was lower than that of the collagen scaffold (P < 0.05). (2) Collagen/heparin sulfate scaffolds had no cytotoxicity, and collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor were more conducive to the proliferation of cerebral microvascular endothelial cells; cerebral microvascular endothelial cells grew well and distributed evenly in the micropores of the collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor. (3) There were a large number of newly formed nerve cells and nerve fibers in the lesions in the scaffold and brain-derived neurotrophic factor groups. The number of nerve cells and the density of nerve fibers in the scaffold group were higher compared with the brain-derived neurotrophic factor group. (4) In the brain-derived neurotrophic factor group, escape latency was shorter (P < 0.01, P < 0.05), quadrant stay time and the number of crossing the platform were higher (P < 0.01, P < 0.05) compared with the scaffold and model groups. (5) The modified neurological severity score in the brain-derived neurotrophic factor group was significantly lower than that in the scaffold and model groups, respectively at postoperative 3-7 weeks (P < 0.05, P < 0.01). (6) These results suggest that collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor can promote neurological and locomotor function recovery in rats after traumatic brain injury.

Key words: traumatic brain injury">, , collagen scaffold">, , collagen/heparin sulfate scaffold">, , brain-derived neurotrophic factor">, , BDNF, water maze">, , cerebral microvascular endothelial cells

CLC Number:

Zhang Jian, Chen Miao, Li Weixin, Ye Yichao, Xu Huiyou, Ma Ke, Chen Xuyi, Sun Hongtao, Zhang Sai. Collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor promote neurological and locomotor function recovery in rats after traumatic brain injury[J]. Chinese Journal of Tissue Engineering Research, 2020, 24(34): 5538-5544.

Figures/Tables 4

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Collagen/heparin sulfate scaffolds loaded with brain-derived neurotrophic factor promote neurological and locomotor function recovery in rats after traumatic brain injury

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