Fast Degrading Bioactive Elastic Scaffold Loaded with Neural Stem Cells Promote Rapid Spinal Cord Regeneration

43 Pages Posted: 25 Oct 2019

See all articles by Zhe Gong

Zhe Gong

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Dong Lei

Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials; Donghua University - International Joint Laboratory for Advanced Fiber and Low-dimension Materials

Chao Yu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Chenggui Wang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Kaishun Xia

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Jiawei Shu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Liwei Ying

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Jiangnan Du

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Xiaopeng Zhou

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Jingkai Wang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Xianpeng Huang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Licheng Ni

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Cong Wang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Jingquan Lin

Zhejiang University - Department of Neurosurgery

Wei Yu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Bin Hu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Liming Li

Zhejiang University - Institute of Pharmaceutics

Jianqing Gao

Zhejiang University - Institute of Pharmaceutics

Yusheng Li

Central South University - Department of Orthopedics

Chuanglong He

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology

Qixin Chen

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Yang Wang

Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials

Fangcai Li

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Juan Carlos Izpisua Belmonte

Salk Institute for Biological Studies - Gene Expression Laboratory

Zhengwei You

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology; Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials

Chengzhen Liang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics; Zhejiang University - Institute of Orthopaedic Research

Abstract

Despite decades of research, spinal cord injury (SCI) still causes irreparable damage to the human body. Key challenges that must be overcome include the glial scars and inflammatory responses within the injury site that hinder the regeneration and extension of neurons following SCI. Transplantation of neural stem cells (NSCs) represents a promising SCI therapy, but these approaches still do not result in comprehensive recovery due to the limited neuronal differentiation of NCSs. Recently, functional scaffolds have been combined with NSCs to treat SCI. Accordingly, we therefore fabricated elastic poly (sebacoyl diglyceride) (PSeD) scaffolds with similar mechanical properties to natural spinal cord. Then, poly (sebacoyl diglyceride)-isoleucine-lysine-valine-alanine-valine-serine (PSeD-IKVAVS) was coated on the PSeD scaffolds to create a bioactive interface. The resultant scaffolds loaded with NSCs were implanted in a complete transection model of SCI in the rat. Graft integrated well with host spinal cord. Grafted NSCs exhibited neuronal differentiation rather than typical scar and very few inflammatory cells infiltrated the lesion site, leading to the significant functional recovery of the rats in 4 weeks. Next, our in vitro analyses showed that degradation products of PSeD-IKVAVS promoted NSCs differentiate into neurons, inhibited neuronal apoptosis induced by hydrogen peroxide, and alleviated inflammation stimulated by lipopolysaccharide (LPS). Overall, we demonstrated PSeD-IKVAVS scaffold containing the characteristics of suitable mechanical properties, bioactivity and fast degradability combined with NSCs would significantly promote neuronal regeneration indicating a novel approach for effectively treating SCI.

Keywords: spinal cord injury, PSeD-IKVAVS, neural stem cell, functional recovery

Suggested Citation

Gong, Zhe and Lei, Dong and Yu, Chao and Wang, Chenggui and Xia, Kaishun and Shu, Jiawei and Ying, Liwei and Du, Jiangnan and Zhou, Xiaopeng and Wang, Jingkai and Huang, Xianpeng and Ni, Licheng and Wang, Cong and Lin, Jingquan and Yu, Wei and Hu, Bin and Li, Liming and Gao, Jianqing and Li, Yusheng and He, Chuanglong and Chen, Qixin and Wang, Yang and Li, Fangcai and Belmonte, Juan Carlos Izpisua and You, Zhengwei and Liang, Chengzhen, Fast Degrading Bioactive Elastic Scaffold Loaded with Neural Stem Cells Promote Rapid Spinal Cord Regeneration. Available at SSRN: https://ssrn.com/abstract=3474004 or http://dx.doi.org/10.2139/ssrn.3474004

Zhe Gong

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Dong Lei

Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials

Shanghai
China

Donghua University - International Joint Laboratory for Advanced Fiber and Low-dimension Materials

Shanghai
China

Chao Yu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Chenggui Wang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Kaishun Xia

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Jiawei Shu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Liwei Ying

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Jiangnan Du

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Xiaopeng Zhou

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Jingkai Wang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Xianpeng Huang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Licheng Ni

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Cong Wang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Jingquan Lin

Zhejiang University - Department of Neurosurgery

China

Wei Yu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Bin Hu

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Liming Li

Zhejiang University - Institute of Pharmaceutics

China

Jianqing Gao

Zhejiang University - Institute of Pharmaceutics

China

Yusheng Li

Central South University - Department of Orthopedics

Changsha
China

Chuanglong He

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology

Shanghai
China

Qixin Chen

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Yang Wang

Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials

Shanghai
China

Fangcai Li

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics

China

Zhejiang University - Institute of Orthopaedic Research

China

Juan Carlos Izpisua Belmonte (Contact Author)

Salk Institute for Biological Studies - Gene Expression Laboratory ( email )

10010 N Torrey Pines Rd
La Jolla, CA 92037
United States

Zhengwei You

Donghua University - College of Chemistry, Chemical Engineering & Biotechnology ( email )

Shanghai
China

Donghua University - State Key Laboratory for Modification of Chemical Fibers and Polymer Materials ( email )

Shanghai
China

Chengzhen Liang

Zhejiang University, School of Medicine, Second Affiliated Hospital, Department of Orthopaedics ( email )

China

Zhejiang University - Institute of Orthopaedic Research ( email )

China

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