Balancing Bacteria-Osteoblast Competition through Selective Physical Puncture and Biofunctionalization of ZnO/Polydopamine/Arginine-Glycine-Aspartic Acid-Cysteine Nanorods

Abstract

Bacterial infection and lack of bone tissue integration are two major concerns of orthopedic implants. In addition, osteoinductivity often decreases and toxicity may arise when antibacterial agents are introduced to increase the antibacterial ability. Here hybrid ZnO/polydopamine (PDA)/arginine-glycine-aspartic acid-cysteine (RGDC) nanorod (NR) arrays are designed and prepared on titanium (Ti) implants to not only enhance the osteoinductivity but also effectively kill bacteria simultaneously, which are ascribed to the selective physical puncture and the biofunctionalization of ZnO/PDA/RGDC nanorods during the competition between bacteria and osteoblasts. That is, owing to the much larger size of osteoblasts than bacteria, the hybrid NRs can puncture bacteria but not damage osteoblasts. Meanwhile, the cytocompatibility can be enhanced through the suppression of both reactive oxygen species and higher Zn²⁺ concentration by the covering of PDA and RGDC. The in vitro results confirm the selective puncture of the bacterial membrane and the better osteoinductivity. In vivo tests also show much higher antibacterial efficacy of the hybrid NRs with far less amounts of lobulated neutrophils and adherent bacteria in the surrounding tissues. In addition, the hybrid NRs also accelerate formation of new bone tissues (20.1% higher than pure Ti) and osteointegration between implants and newly formed tissues (32.0% higher than pure Ti) even in the presence of injected bacteria. This work provides a surface strategy for designing implants with desirable ability of osseointegration and infection prevention simultaneously, which will exhibit tremendous clinical potential in orthopedic and dental applications.

Keywords: ZnO nanorod; antibacterial; implants; osseointegration; physical puncture.