Antibacterial and Angiogenic Copper Phosphate-Modified Carbonate Apatite Honeycomb Plugs for Enhanced Gingival and Alveolar Bone Regeneration
Koichiro Hayashi, Eri Teramoto, Ahmad Nazir Taleb Alashkar, Zhanrui Lou, Masafumi Moriyama, Kunio Ishikawa
Abstract
After tooth extraction, socket preservation is essential to minimize alveolar bone loss and improve implant success. However, conventional granular graft materials lack gingival regenerative and antibacterial properties, pose a risk of migration, and often require additional procedures, which complicate treatment and reduce clinical efficacy. To address these limitations, we developed a cylindrical carbonate apatite (CAp) plug with a honeycomb structure surface-modified with copper phosphate (CuP). The CAp composition offers inherent osteoconductivity, while CuP imparts antibacterial and angiogenic properties. The honeycomb structure promotes the ingrowth of bone and blood vessels, while the cylindrical shape enhances surgical handling and minimizes material migration. Together, the optimized composition, structure, and shape contribute to infection prevention and enhanced tissue regeneration. In vitro, the honeycomb plugs with 500 ppm of Cu exhibited strong antibacterial effects against Streptococcus mutans and methicillin-resistant Staphylococcus aureus without cytotoxicity toward human cells. These honeycomb plugs also promoted osteogenic differentiation of mesenchymal stem cells and endothelial cell growth. In vivo, despite migration of CAp granules, the honeycomb plugs remained stable, prevented fibrous tissue invasion, and achieved superior regeneration of both the gingiva and bone. The plugs completely repaired gingival defects and were resorbed and replaced with bone within 4 weeks, eliminating long-term risks associated with residual materials. These results indicate that the developed material effectively addresses the limitations of conventional grafts and demonstrates significant potential for improving clinical outcomes in socket preservation.