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

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.