Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection

AUTHORS

Ying Yang, Min Li, Bixia Zhou, Xulei Jiang, Dou Zhang, Hang Luo

ABSTRACT

Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing an effective surface modification strategy for implants is urgently needed. Here, a novel nanoplatform (GO/Ga) consisting of graphene oxide (GO) and gallium nanoparticles (GaNPs) was reported, followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms, cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis. In addition, the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified. Moreover, an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites. Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad, MAPK and NF-κB signaling pathways. The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections, reduced osteolysis, promoted osseointegration located in implant-bone interfaces, and resulted in satisfactory biocompatibility. In summary, this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.

TiO2 Nanocoatings with Controllable Crystal Type and Nanoscale Topography on Zirconia Implants to Accelerate Bone Formation

AUTHORS

Nan Li, Zhichao Liu, Guanqi Liu, Zhi Wang, Xianwei Guo, Chuanbin Guo, Jianmin Han

ABSTRACT

In dentistry, zirconia implants have emerged as a promising alternative for replacing missing teeth due to their superior aesthetic performance and chemical stability. To improve the osseointegration of zirconia implants, modifying their surface with hierarchical micro/nanotopography and bioactive chemical composition are two effective ways. In this work, a microscale topography was prepared on a zirconia surface using hydrofluoric acid etching, and then a 50 nm TiO2 nanocoating was deposited via atomic layer deposition (ALD). Subsequently, an annealing treatment was used to transform the TiO2 from amorphous to anatase and simultaneously generate nanoscale topography. Various investigations into the coating surface morphology, topography, wettability, and chemical composition were carried out using scanning electron microscopy, white light interferometry, contact-angle measurement, X-ray diffraction, and X-ray photoelectron spectroscopy. In addition, in vitro cytocompatibility and osteogenic potential performance of the coatings were evaluated by human bone marrow mesenchymal stem cells (hBMSCs), and in vivo osseointegration performance was assessed in a rat femoral condyle model. Moreover, the possible mechanism was also investigated. The deposition of TiO2 film with/without annealing treatment did not alter the microscale roughness of the zirconia surface, whereas the nanotopography changed significantly after annealing. The in vitro studies revealed that the anatase TiO2 coating with regular wavelike nanostructure could promote the adhesion and proliferation of osteoblasts and further improve the osteogenic potential in vitro and osseointegration in vivo. These positive effects may be caused by nanoscale topography via the canonical Wnt/β-catenin pathway. The results suggest that using ALD in combination with annealing treatment to fabricate a nanotopographic TiO2 coating is a promising way to improve the osteogenic properties of zirconia implants.

Bio-clickable mussel-inspired peptides improve titanium-based material osseointegration synergistically with immunopolarization-regulation

AUTHORS

Jie Suna, Yingkang Huang, Huan Zhao, Junjie Niu, Xuwei Ling, Can Zhu, Lin Wang, Huilin Yang, Zhilu Yang, Guoqing Pan, Qin Shi

ABSTRACT

Upon the osteoporotic condition, sluggish osteogenesis, excessive bone resorption, and chronic inflammation make the osseointegration of bioinert titanium (Ti) implants with surrounding bone tissues difficult, often lead to prosthesis loosening, bone collapse, and implant failure. In this study, we firstly designed clickable mussel-inspired peptides (DOPA-N3) and grafted them onto the surfaces of Ti materials through robust catechol-TiO2 coordinative interactions. Then, two dibenzylcyclooctyne (DBCO)-capped bioactive peptides RGD and BMP-2 bioactive domain (BMP-2) were clicked onto the DOPA-N3-coated Ti material surfaces via bio-orthogonal reaction. We characterized the surface morphology and biocompatibility of the Ti substrates and optimized the osteogenic capacity of Ti surfaces through adjusting the ideal ratios of BMP-2/RGD at 3:1. In vitro, the dual-functionalized Ti substrates exhibited excellent promotion on adhesion and osteogenesis of mesenchymal stem cells (MSCs), and conspicuous immunopolarization-regulation to shift macrophages to alternative (M2) phenotypes and inhibit inflammation, as well as enhancement of osseointegration and mechanical stability in osteoporotic rats. In summary, our biomimetic surface modification strategy by bio-orthogonal reaction provided a convenient and feasible method to resolve the bioinertia and clinical complications of Ti-based implants, which was conducive to the long-term success of Ti implants, especially in the osteoporotic or inflammatory conditions.