Long-rod nano-hydroxyapatite derived G-LR-HA@TZ acts as a multifunctional regenerative tool for periodontal bone

While hydroxyapatite (HA) is widely used in bone tissue engineering due to its biomimetic mineral composition, the influence of its nanoscale morphology on biological responses and surface functionalization has not been sufficiently investigated. Herein, spherical, short-rod, and long-rod HA nanoparticles were systematically evaluated for biofunctionalization via a metal-polyphenol network (MPN) coating composed of tannic acid (TA) and zinc ion (Zn²⁺). Among them, the long-rod HA (LR-HA) topology proved optimal, establishing a clear morphology-function relationship that maximized biological efficacy. Benefiting from the synergistic effect of its unique long-rod morphology and the MPN coating, the resultant LR-HA@TZ exhibited strong antioxidant capability, and effectively promoted macrophage polarization from the M1 to the M2 phenotype via activation of the integrin/FAK/RhoA/ROCK signaling pathway. Consequently, conditioned media from LR-HA@TZ-treated macrophages most effectively reversed the lipopolysaccharide derived from Porphyromonas gingivalis (Pg. LPS)-induced suppression of osteogenesis in bone marrow mesenchymal stem cells (BMSCs) and stimulated angiogenesis in human umbilical vein endothelial cells (HUVECs). Based on these findings, we integrated LR-HA@TZ into an injectable dual-network hydrogel and developed into G-LR-HA@TZ, a material exhibiting self-healing, tissue-adhesive, antibacterial, and hemostatic capabilities. In a rat periodontitis model, G-LR-HA@TZ effectively attenuated alveolar bone resorption, suppressed osteoclast activity, and promoted bone tissue regeneration through immunomodulation, outperforming the clinically commonly used Periocline® (minocycline ointment). This study establishes a pivotal role for HA nanoparticle morphology in determining functionalization efficacy and immune regulation, translating this insight into a novel regenerative strategy for periodontal bone repair via microenvironment reprogramming.