Advances in applications of chiral biomaterials in bone regeneration

Chirality, a fundamental property of nature, plays a pivotal role in regulating cell fate and promoting tissue regeneration. Owing to their distinctive stereochemical properties and the inherent chiral selectivity of biological systems, chiral biomaterials offer novel strategies to address the immense clinical demands for tissue regeneration. However, prior research lacks a systematic summary of chiral biomaterials for tissue regeneration, particularly concerning bone regeneration, thereby impeding research progress and clinical translation. In this review, we first introduce the classification and fabrication of mainstream chiral biomaterials, including chiral nanoparticles, chiral supramolecular hydrogels, and chiral topography. We then discuss the intrinsic hierarchical chirality of native bone and elucidate how chiral biomaterials synergistically promote bone repair by modulating the immune microenvironment, osteogenic differentiation, vascularization, and neural regeneration. We also discuss the uderlying mechanisms. Finally, we outline the key technical, biological, and translational challenges and propose directions for future research. Collectively, this review advances the mechanistic understanding of chiral biomaterials and provides a rational framework for their design and clinical application in promoting bone regeneration.