Three-dimensional printed PCL/nHA scaffolds promote soft tissue functional fibrosis to repair chest wall defect via Piezo1/Ca2+ signal during respiratory motion

The formation of a hardened fibrous membrane through in situ degradation of polycaprolactone (PCL) in soft tissues has emerged as a promising alternative to conventional rigid bone implants for chest wall reconstruction. However, strategies to enhance the mechanical integrity and biological performance of such fibrous constructs remain limited. While nano-hydroxyapatite (nHA) is known to promote osteoblast proliferation and mineralization, its role in regulating fibroblast behavior remains unclear, particularly within a dynamically strained environment mimicking respiratory motion. In this study, we developed PCL scaffolds incorporating various concentrations of nHA using fused deposition modeling (FDM). The PCL/10 wt% nHA scaffold exhibited optimal mechanical properties and significantly enhanced fibroblast proliferation, adhesion, and extracellular matrix deposition in vitro. Notably, higher nHA content led to excessive Piezo1 activation, resulting in Ca 2+ overload and increased fibroblast apoptosis. Under dynamic mechanical stimulation, the PCL/10 wt% nHA scaffold markedly promoted fibroblast functionality and tissue fibrosis, facilitating robust soft tissue hardening in vivo. Mechanistic investigations revealed that the Piezo1/TGF-β1 signaling axis plays a central role in mediating fibroblast responses to cyclic shear stress. These findings demonstrate that the PCL/10 wt% nHA scaffold effectively supports tissue-engineered structural reinforcement through fibroblast-driven fibrosis, presenting a biodegradable and mechanically adaptive approach with potential for future chest wall repair applications. In this study, PCL/nHA composite scaffolds were designed and fabricated using fused deposition modeling technology. These scaffolds not only exhibit excellent mechanical properties but also significantly promote the proliferation and fibrosis of fibroblasts. As a biodegradable implant, it supports the chest wall structure by stimulating the proliferation and fibrosis of soft tissues, providing a promising strategy for future chest wall reconstruction. • PCL/nHA implants drive fibrotic integration in soft tissue, offering a degradable alternative to rigid chest wall implants. • 10 wt% nHA activates Piezo1/TGF-β1 for fibrosis, while excess causes Piezo1-mediated calcium overload and apoptosis. • Dynamic respiratory shear forces synergize with PCL/nHA to enhance fibroblast function and soft tissue integrity.