Aligned Electrospun Fibers Inducing Cell and Nuclear Morphology Remodeling via Ras-Associated Protein 1/Yes-Associated Protein Signaling Enhances Bone Regeneration

Abstract

The topographical features of biomaterials play pivotal roles in modulating bone regeneration by enhancing the osteogenic potential of bone marrow-derived mesenchymal stem cells (BMSCs) through cytoskeletal-nuclear dynamics. However, the precise mechanisms underlying the interplay between topography-induced cell morphology modulation and cytoskeletal-nuclear responses remain poorly understood. In this study, we fabricated electrospun fiber membranes with distinct aligned and random topographies and observed a significant enhancement in the osteogenic differentiation of BMSCs in vitro on the aligned membranes. RNA sequencing analysis revealed the critical involvement of cytoskeletal reorganization, focal adhesion, and the Rap1 signaling pathway in this process. Specifically, cell elongation driven by the aligned topography activated the p130Cas/Crk/Rap1 pathway, which in turn modulated mitogen-activated protein kinase (MAPK) signaling and cytoskeletal rearrangement. This cytoskeletal remodeling induced nuclear deformation and enhanced the nuclear translocation of Yes-associated protein (YAP), synergistically promoting osteogenesis. Finally, in vivo experiments further confirmed the superior bone regeneration capacity of aligned fiber membranes in a rat calvarial defect model. These findings highlight the importance of the topographic features of aligned fibers in regulating cellular and nuclear morphology to enhance bone regeneration, suggesting a novel and effective strategy for tissue engineering applications.

Keywords

Electrospinning / Aligned fiber / Cell morphological remolding / Osteogenesis / Bone regeneration

References

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Funding

National Natural Science Foundation of China(32271379)

Shanghai's Top Priority Research Center(2022ZZ01017)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China