Abstract
Recent studies have shown the importance of cell–substrate interaction on neurone outgrowth, where the Young’s modulus of the matrix plays a crucial role on the neurite length, migration, proliferation, and morphology of neurones. In the present study, PC12 cells were selected as the representative neurone to be cultured on hydrogel substrates with different stiffness to explore the effect of substrate stiffness on the neurone outgrowth. By adjusting the concentration of gelatin methacryloyl (GelMA), the hydrogel substrates with the variation of stiffnesses (indicated by Young’s modulus) from approximately 3–180 KPa were prepared. It is found that the stiffness of GelMA substrates influences neuronal outgrowth, including cell viability, adhesion, spreading, and average neurite length. Our results show a critical range of substrate’s Young’s modulus that support PC12 outgrowth, and modulate the cell characteristics and morphology. The present study provides an insight into the relationship between the stiffness of GelMA hydrogel substrates and PC12 cell outgrowth, and helps the design and optimization of tissue engineering scaffolds for nerve regeneration.
Highlights
The treatment of peripheral nerve injury is a global clinical problem, which causes enormous economic burden to the society [1]
Primary rat cortical neurones (RCN) were cultured on soft and stiff substrates with Young’s modulus of 5–500 KPa, respectively, to investigate the role of the matrix rigidity on the formation and activity of cortical neuronal networks, and the results showed that migration of cortical neurones is enhanced on soft substrates, leading to a faster formation of neuronal networks [7]
Indicating that the stiffness of the hydrogels was reinforced by the gelatin methacryloyl (GelMA) concentration
Summary
The treatment of peripheral nerve injury is a global clinical problem, which causes enormous economic burden to the society [1]. Penetration, ischemia, traction as well as radiation, vibration and electric shock are common causes of peripheral nerve injuries [2]. The development of tissue-engineered scaffolds has become a popular current avenue to repair peripheral nerve injuries [3,4]. In order to improve the efficiency of these treatments, it is essential to have a better understanding of how nerve cells interact with scaffolds and how these interactions affect cellular behavior. Since the stiffness of scaffold material varies significantly, the scaffold stiffness may play an important role in nerve regeneration
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