Structural alignment guides oriented migration and differentiation of endogenous neural stem cells for neurogenesis in brain injury treatment

Yi Chai; He Zhao; Shuhui Yang; Xiaohan Gao; Zheng Cao; Jiaju Lu; Qingling Sun; Wei Liu; Zhe Zhang; Junyi Yang; Xuelin Wang; Tuoyu Chen; Xiangdong Kong; Antonios G Mikos; Xiaohua Zhang; Yuqi Zhang; Xiumei Wang

doi:10.1016/j.biomaterials.2021.121310

Structural alignment guides oriented migration and differentiation of endogenous neural stem cells for neurogenesis in brain injury treatment

Biomaterials. 2022 Jan:280:121310. doi: 10.1016/j.biomaterials.2021.121310. Epub 2021 Dec 3.

Authors

Yi Chai¹, He Zhao², Shuhui Yang³, Xiaohan Gao⁴, Zheng Cao³, Jiaju Lu⁵, Qingling Sun², Wei Liu⁶, Zhe Zhang³, Junyi Yang³, Xuelin Wang⁷, Tuoyu Chen⁴, Xiangdong Kong⁵, Antonios G Mikos⁸, Xiaohua Zhang⁹, Yuqi Zhang¹⁰, Xiumei Wang¹¹

Affiliations

¹ State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China; Department of Neurosurgery, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 100040, China; Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai, 200127, China.
² Department of orthopacdic III, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
³ State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China.
⁴ Department of Neurosurgery, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 100040, China.
⁵ School of Materials Science and Engineering, Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou, 310018, China.
⁶ Department of Neurosurgery, The First Hospital of Hebei Medical University, Hebei, 050000, China.
⁷ School of Medical Science and Engineering, Beihang University, Beijing, 100191, China.
⁸ Department of Bioengineering, Rice University, Houston, TX, 77030, USA.
⁹ Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, No. 160, Pujian Road, District Pudong, Shanghai, 200127, China.
¹⁰ Department of Neurosurgery, Yuquan Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 100040, China. Electronic address: doctorzyq@126.com.
¹¹ State Key Laboratory of New Ceramics and Fine Processing, Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China. Electronic address: wxm@mail.tsinghua.edu.cn.

PMID: 34890972
DOI: 10.1016/j.biomaterials.2021.121310

Abstract

Radial glia (RG) cells that align in parallel in the embryonic brain are found to be able to guide the directed migration of neurons in response to brain injury. Therefore, biomaterials with aligned architectures are supposed to have positive effects on neural migration and neurogenic differentiation for brain injury repair that are rarely addressed, although they have been widely demonstrated in spinal cord and peripheral nerve system. Here, we present a highly biomimetic scaffold of aligned fibrin hydrogel (AFG) that mimics the oriented structure of RG fibers. Through a combination of histological, behavioral, imaging, and transcriptomic analyses, we demonstrated that transplanting the AFG scaffold into injured cortical brains promotes effective migration, differentiation, and maturation of endogenous neural stem cells, resulting in neurological functional recovery. Therefore, this study will light up a new perspective on applying an aligned scaffold to promote cortical regeneration after injury by inducing endogenous neurogenesis.

Keywords: Aligned fibrin hydrogel; Brain injury; Neuro tissue engineering; Neurogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / pathology
Brain Injuries* / therapy
Cell Differentiation
Humans
Neural Stem Cells* / pathology
Neurogenesis
Spinal Cord Injuries* / pathology
Spinal Cord Injuries* / therapy