Chiral nanoparticles drive enantiomer-specific osteogenic differentiation of stem cells and accelerate bone regeneration
- Yuwen Wang
- Zheng Zhong
- Zeqing Li
- Yuecong Guo
- Christina Sin U. Ieong
- Tao Yao
- Boguang Yang
- Ning Zhang
- Songlin He
- Zhilong Zhou
- Jun Liu
- Runxuan Cai
- Yaling Wang
- Chung Hang Jonathan Choi
- Chuanbin Mao
- Denghui Xie
- Zhifeng Huang
- Bo Liu
- Maobin Xie
- Chunying Chen
- Zhong Alan Li
2026-06-10
Precise control over stem cell differentiation is of crucial importance in regenerative medicine, such as stem cell–based bone repair. Chiral nanoparticles (NPs) exhibit enantiomer-dependent interactions with stem cells, providing a promising strategy for guiding cell behaviors. Here, we investigated the role of chiral NPs in modulating osteogenic differentiation of stem cells. L-CF-NPs, D-CF-NPs, and A-CF-NPs with controllable nanoscale chirality were synthesized to investigate the effect of enantioselectivity on stem cell fate. In vitro, L-CF-NPs resulted in the highest cellular uptake through clathrin-mediated, integrin-involved endocytosis. This led to the most pronounced up-regulation of osteogenic marker expression, mineralization (via MAPK/JNK/ERK), and angiogenic marker expression. In vivo, volumetric 3D-bioprinted scaffolds incorporating L-CF-NPs resulted in the fastest bone regeneration in a rat model of critical-size bone defects. This work establishes nanoscale chirality as a design parameter for biomaterials, offering a promising approach to regenerating bone and other tissues.