Mechanically Guided Cell Fate Regulation In Bone Organoids And Application

This study explores the impact of the dynamic mechanical environment on bone organoids formation, aiming to modulate cell fate to construct functional bone organoids and promote the repair and regeneration of bone defects. Finite element was performed to observe the stress levels within the organoids. Cytoplasmic staining was conducted to assess the impact on cell deformation. Alkaline phosphatase staining, real-time polymerase chain reaction, and immunofluorescence staining were employed to evaluate the effects on osteogenic differentiation and immune polarization in the bone organoids. The organoids were implanted into a femoral defect model, with its repair efficacy examined by Micro-CT and histological analysis. Greater mechanically guided deformation leads to higher internal stress in bone organoids and more pronounced elliptical deformation of the cells. Mechanical guidance promoted the osteogenic differentiation of bone marrow mesenchymal stem cells, inhibited the M1 pro-inflammatory polarization, and enhanced their M2 anti-inflammatory polarization of macrophages. Bone organoids constructed from mesenchymal stem cells and macrophages under dynamic mechanical stimulation exhibited no significant statistical differences in bone volume fraction and trabecular number when repairing in vivo bone defects compared with autologous bone. This study regulates cell fate through appropriate mechanical guidance to construct bone organoids. The cells within the organoids exhibit a positive response to dynamic mechanical stimulation, with a marked enhancement in osteogenic differentiation and the development of an anti-inflammatory immune microenvironment. Bone organoids constructed via mechanically guided regulation of cell fate exhibit bone defect repair efficacy comparable to that of autologous bone.