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

Abstract

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 Ca²⁺ 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.