Dynamic stimulation of piezoelectric scaffolds enhances osteogenesis-related biological responses via electro-mechanical sensitive channels and cytoskeletal remodeling.

Abstract

The inherent electrophysiological properties of natural bone tissue and the enhancement of bone healing via endogenous electric field highlight the importance of piezoelectric biomaterials for neovascularized bone regeneration. However, current research predominantly utilizes static conditions for in vitro cell studies and relies largely on non-load-bearing calvarial defect models for animal evaluations. To investigate how piezoelectric scaffolds influence cell behaviors under dynamic mechanical stimulation, this study employs a custom-made circulating compression system to perform dynamic cell culture experiments on a piezoelectric cryogel scaffold. The scaffold consists of methacrylated gelatin (GelMA) combined with piezoelectric whitlockite (PWH), exhibiting outstanding shape deformation-recovery stability under cyclic mechanical loading. Mechanical stimulation was applied at two distinct frequencies (1 Hz and 2 Hz) to simulate conditions similar to walking and jogging. Bone marrow mesenchymal stromal cells (BMSCs) seeded onto the scaffold were assessed for their potential to undergo osteogenic, angiogenic, and neurogenic differentiation in response to dynamic mechanical stimuli. Notably, the electrical signals generated by the scaffold significantly influence BMSCs proliferation and differentiation. These effects are mediated through mechanisms including activation of ionic channels, enhanced influx of Ca²⁺/Mg²⁺ ions, cytoskeletal remodeling, and actomyosin contractility. This study provides clear evidences linking scaffold piezoelectricity with specific cellular responses essential for osteogenesis and bone regeneration. Overall, the findings offer valuable insights into the roles of electroactive biomaterials in tissue repair, guiding future development of advanced scaffolds for bone tissue engineering.