Elastic Modulus of Chitosan/Polycaprolactone Scaffolds Exerts an Osteogenic Effect on EMSCs In Vitro and In Vivo through the YAP Signaling Pathway

Ectomesenchymal stem cells (EMSCs) loaded with bone tissue-engineered scaffolds are considered a promising strategy for treating bone defects. However, the therapeutic efficacy of this approach is not solely dependent on the biological characteristics of EMSCs but also on the physicochemical properties of the scaffold. In particular, the elastic modulus of the scaffold plays a crucial role, yet its effects on the biological behavior of EMSCs remain poorly unclear. In this study, we constructed a composite scaffold from chitosan and polycaprolactone, which allowed an adjustable elastic modulus. We investigated the effects of these scaffolds on the adhesion, proliferation, and osteogenic differentiation of EMSCs in vitro. A suitable composite scaffold for EMSC osteogenic differentiation was first identified through early and late osteogenesis. Additionally, the composite scaffold was confirmed to promote the osteogenic differentiation of EMSCs through piezo1/YAP signaling. Finally, we demonstrated that the composite scaffold loaded with EMSCs ultimately promoted skull bone regeneration in a rat model. These findings provide valuable insights into the strong application prospects of EMSC-loaded scaffolds for bone defect therapy.