Chirality Regulates Bone Regeneration through Mechanoresponse and Immunoregulation

As an omnipresent occurrence in the natural world, chirality plays a crucial role in numerous biological and physiological processes. Therefore, incorporation of chirality into biointerface materials has been emerging as a research hotspot in the development of regenerative biomaterials. Nevertheless, how chiral biointerface materials interact with biological organisms remains poorly understood. In the current study, a bioinspired chiral self-assembled nanohydroxyapatite material is developed for bone regeneration using a distraction osteogenesis model. We found that the left-handed chirality, rather than the right-handed chirality, possessed the greatest heightened ability for bone regeneration. Molecular mechanism research reveals that the left-handed chirality can activate mechanosensitive pathways to promote Ca²⁺ influx, subsequently enhancing macrophage type-2 polarization through phosphorylation of signal transducer and activator of transcription (STAT6), which eventually stimulates bone regeneration by harnessing the synergistic effects of angiogenesis and osteogenesis. These findings provide additional insights into the underlying mechanism of chiral recognition between biological systems and biointerface materials, offering alternative pathways for the development of biomaterials.