Cell-specific responses to changes in size-scale and orientation of architectural cues in polymeric scaffolds: Insights from human mesenchymal stem cells and endothelial cells

Nov 6, 2025Tissue & cell

How human stem and blood vessel cells respond to changes in size and direction of scaffold structures

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

Variations in fiber size scale and orientation within electrospun scaffolds significantly influence the behavior of human mesenchymal stem cells (MSCs) and endothelial cells (ECs).

The viscoelastic properties of the scaffold membrane affect cell attachment, spreading, and migration.
MSCs are more responsive to matrix stiffness and architectural cues compared to ECs.
ECs exhibit a greater dependence on size scale and fiber orientation for their behavior.
MSCs showed enhanced migration along anisotropic microfibers, while ECs migrated more efficiently on anisotropic nanofibers.
The study indicates that scaffold design should be tailored to optimize cellular responses based on cell type.

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Biomaterial scaffolds play a crucial role in directing cellular behaviour and influencing tissue regeneration outcomes. Understanding how specific architectural cues influence cell attachment, spreading, and migration is essential for optimizing scaffold design in tissue engineering applications. In this study, we investigated how variations in fiber size scale and orientation within electrospun scaffolds influence the behaviour of human mesenchymal stem cells (MSCs) and endothelial cells (ECs). Our findings demonstrate that the inherent viscoelastic property of the membrane and variations in the size scale and orientation of architectural cues significantly influence the attachment, spreading, and migration of both MSCs and ECs in a cell-type-dependent manner. MSCs were more sensitive to matrix stiffness and architectural cues, while ECs responded more to size scale and orientation, and these sensitivities governed their attachment, spreading, and migration. Specifically, MSCs demonstrated enhanced migration along anisotropic microfibers, highlighting the influence of the matrix stiffness and fiber orientation at the microscale. In contrast, ECs migrated more efficiently on anisotropic nanofibers, indicating a size-scale and orientation-dependent response where nanoscale cues played a crucial role in guiding endothelial cell mobility. These findings highlight the distinct, cell-type-specific influence of size and orientation based architectural cues on MSC and EC behaviour, emphasizing the importance of tailoring scaffold design to optimize cellular responses.

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Cell-specific responses to changes in size-scale and orientation of architectural cues in polymeric scaffolds: Insights from human mesenchymal stem cells and endothelial cells

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