Abstract
Understanding the influence of the mechanical environment on neurite behavior is crucial in the development of peripheral nerve repair solutions, and could help tissue engineers to direct and guide regeneration. In this study, a new protocol to fabricate physiologically relevant hydrogel substrates with controlled mechanical cues is proposed. These hydrogels allow the analysis of the relative effects of both the absolute stiffness value and the local stiffness gradient on neural cell behavior, particularly for low stiffness values (1–2 kPa). NG108‐15 neural cell behavior is studied using well‐characterized collagen gradient substrates with stiffness values ranging from 1 to 10 kPa and gradient slopes of either 0.84 or 7.9 kPa mm−1. It is found that cell orientation is influenced by specific combinations of stiffness value and stiffness gradient. The results highlight the importance of considering the type of hydrogel as well as both the absolute value of the stiffness and the steepness of its gradient, thus introducing a new framework for the development of tissue engineered scaffolds and the study of substrate stiffness.
Highlights
Understanding the influence of the mechanical environment on neurite underpin conduits that support and guide behavior is crucial in the development of peripheral nerve repair solutions, and could help tissue engineers to direct and guide regeneration
For the analysis of cell behavior (Section 3.3), the continuous stiffness gradients were each segmented in three areas (I–II–III)
Statistical analysis showed no significant difference between the Control and the softest part of each gradient gel (ILower and IHigher)
Summary
Understanding the influence of the mechanical environment on neurite underpin conduits that support and guide behavior is crucial in the development of peripheral nerve repair solutions, and could help tissue engineers to direct and guide regeneration. A new protocol to fabricate physiologically relevant hydrogel substrates with controlled mechanical cues is proposed. The results highlight the importance of considering the type of hydrogel as well as both the absolute value of the stiffness and the steepness of its gradient, introducing a new framework for the development of tissue engineered scaffolds and the study of substrate stiffness. Site morbidity and limited availability.[2] Improved peripheral Recent studies have characterized the mechanosensitivity of nerve repair strategies need to be developed and one of the PNS neural cells on various stiffness substrates. Emerging research avenues in tissue engineering is the study Rosso et al.[4] investigated the behavior of dorsal root ganglion (DRG) explants when exposed to 1, 10, and 20 kPa substrates and observed variations in the extension pattern and direc-
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