Chirality‐Induced Hydroxyapatite Manipulates Enantioselective Bone‐Implant Interactions Toward Ameliorative Osteoporotic Osseointegration

Abstract Inspired by the fundamental attribute of chirality in nature, chiral‐engineered biomaterials now represent a groundbreaking frontier in biomedical fields. However, the integration of chirality within inorganic materials remains a critical challenge and developments of chirality‐induced bionic bone implants are still in infancy. In this view, novel chiral hydroxyapatite (CHA) coated Ti alloys are successfully synthesized by a sophisticated chiral molecule‐induced self‐assembly method for the first time. The obtained samples are characterized by stereospecific L‐/D‐/Rac‐chiral hierarchical morphology, nanotopography rough surfaces, improved hydrophilicity, and bioactivity. Following implantation into rat femoral condyle defects, the distinct stereospecific chiral hierarchical structures exhibit highly enantioselective bone‐implants interactions, wherein the left‐handed chirality of L‐CHA strongly promotes osteoporotic osseointegration and vice versa for right‐handed chirality of D‐CHA. Consistently, in vitro assays further validate the superior enantiomer‐dependent osteoporotic osseointegration ability of L‐CHA, mainly by manipulating desired immunomodulation coupled with enhanced neurogenesis, angiogenesis, and osteogenesis. Moreover, as analyzed by transcriptomic RNA‐seq, a new discovery of down‐regulated IL‐17 signaling pathway is considered predominately responsible for the desired immunomodulation ability of L‐CHA. These results provide new insights into biological multifunctionality and mechanism underlying L‐chirality's roles for bone healing, thus may inspiring developments of new generation of chiral biomaterials.