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RESEARCH ARTICLE

In vitro model of the glial scar

Ao Fang , Zhiyan Hao , Ling Wang , Dichen Li *, Jiankang He , Lin Gao , Xinggang Mao ,
1,2
1,2
1,2
1,2
3
1,2
1,2
Rubén Paz 4
1 School of Mechanical Engineering, Xi’an Jiaotong University, Xi’an, ShaanXi 710054, China
2 State Key Laboratory for Manufacturing System Engineering, School of Mechanical Engineering, Xi’an Jiaotong
University, Xi’an, ShaanXi 710054, China
3 Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi Province 710032, China
4 Departamento de Ingeniería Mecánica, Universidad de Las Palmas de Gran Canaria, 35017 Las Palmas de Gran Canaria,
Spain
Abstract: The trauma of central nervous system (CNS) can lead to glial scar, and it can limit the regeneration of neurons at
the injured area, which is considered to be a major factor affecting the functional recovery of patients with CNS injury. At
present, the study of the glial scar model in vitro is still limited to two-dimensional culture, and the state of the scar in vivo
cannot be well mimicked. Therefore, we use a collagen gel and astrocytes to construct a three-dimensional (3D) model in vitro
to mimic natural glial scar tissue. The effects of concentration changes of astrocytes on cell morphology, proliferation, and
tissue performance were investigated. After 8 days of culture in vitro, the results showed that the tissue model contracted, with
a measured shrinkage rate of 4.5%, and the compressive elastic modulus increased to nearly 4 times. Moreover, the astrocytes
of the 3D tissue model have the ability of proliferation, hyperplasia, and formation of scar clusters. It indicates that the model
we constructed has the characteristics of glial scar tissue to some extent and can provide an in vitro model for the research of
glial scar and brain diseases.

Keywords: Glial scar; In vitro; Three-dimensional
*Correspondence to: Dichen Li, State Key Laboratory for Manufacturing System Engineering, School of Mechanical Engineering, Xi’an Jiaotong
University, Xi’an, ShaanXi 710054, China; xjtudcli@sina.com
Received: July 10, 2019; Accepted: July 18, 2019; Published Online: July 30, 2019

Citation: Fang A, Hao Z, Wang L, et al., 2019, In vitro model of the glial scar. Int J Bioprint, 5(2): 235. http://dx.doi.
org/10.18063/ijb.v5i2.235

1. Introduction in CNS tissue repair . On the contrary, a glial scar plays
[1]
an important role. A glial scar is mainly caused by CNS
The central nervous system (CNS) is very complex, and trauma. The formation of a glial scar is mainly caused by
trauma, disease, and infection of it is urgent problems
to be solved, all of them are basically inseparable from the action of astrocytes, such as barrier forming, mitosis,
[7,8]
resulting scars. Two types of scarring tissue are formed and migration to the injured area to fill space . Astrocytes
in the injured CNS. One is a fibrotic scar that is formed play a significant role in CNS injury response [9,10] . The
by fibroblasts, and the other is a glial scar, which consists response of them varies with the location of the injury.
of astrocytes, microglia, and other glial precursor cells . The ones near the damaged tissues become hypertrophic,
[1]
Once CNS is injured, fibroblasts invade the region hyperplastic, and deformed. Moreover, the glial fibrillary
of the lesion and interact to form glia limitans with acidic protein (GFAP) goes up [11,12] , the cells migrate [13-15] ,
astrocytes [2-4] . However, fibrotic scars do not always exist and the dense scar tissue begin to isolate the damaged area
in CNS tissue repair, such as no fibrotic scar formation from the surrounding healthy tissue [16-18] . In general, the
during the astrocytic reconstruction of the blood-brain morphology, proliferation, and migration of astrocytes are
barrier [5,6] . Therefore, fibrotic scar does not play a key role the main causes of glial scar formation.

In vitro model of the glial scar © 2019 Fang A, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-
NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction
in any medium, provided the original work is properly cited.
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