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.

Decaffeinated green tea extract as a nature-derived antibiotic alternative: An application in antibacterial nano-thin coating on medical implants

AUTHORS

Jihyo Park, Lianhua Chi, Hee-Young Kwon, Jisoo Lee, Seunghwi Kim, Seonki Hong

ABSTRACT

Plant-derived polyphenols have emerged as molecular building blocks for biomedical architectures. However, the isolation of polyphenols from other components requires labor-intensive procedures, which increases costs and often raises environmental concerns. Here, we suggest that decaffeination can be a convenient and cost-effective method for enhancing the antibacterial performance of polyphenol-rich tea extracts. As a demonstration, we compared the properties of a nano-thin coating made of decaffeinated (dGT coating) and raw green tea extract (GT coating). The dGT coating exhibited enhanced antibacterial performance with regard to bacterial killing and prevention of bacterial attachment compared with the GT coating. Moreover, the chemical reactivity of the dGT coating was further utilized for secondary modifications, which enhanced the overall antibacterial performance of the modified surface. Given its intrinsic low toxicity, we envision that the developed antibacterial coating is ready for the next steps toward application in real clinical settings.

Preliminary study on the osseointegration effects of contactless automated implant cavity preparation via femtosecond laser ablation

AUTHORS

Shanshan Liang, Jianqiao Zheng, and Fusong Yuan

ABSTRACT

Microrobots were used to control the femtosecond laser ablation of bone tissues to prepare implant cavities for dental implant surgery. The method was optimized through depth-of-cut experiments of ex vivo rabbit femurs, and the optimized method was used to prepare implant cavities on the left femurs of eight live rabbits. A power of 10 W and a scanning rate of 4000 mm/s were found to be optimal. After seven days of osteoinduction, the expression of collagen type I was significantly higher in the experimental group than in the control group (manually drilled implant cavities). The bone–implant contacts of the experimental group at 4 and 8 weeks were 9.65% and 23.08%, respectively.

Experimental Study of the Effects of Hypoxia Simulator on Osteointegration of Titanium Prosthesis in Osteoporotic Rats

AUTHORS

Jiangfeng Liu, Huijun Kang, Jiangfeng Lu, Yike Dai, Fei Wang

ABSTRACT

Purpose: Poor osseointegration is the key reason for implant failure after arthroplasty, whether in osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine(DFO) can accelerate osteogenesis by activation of the hypoxia signal pathway. The purpose of this study is to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with titanium prosthesis in the bones of osteoporotic rats.

Materials and Methods: 90 female sprague-dawley rats were used for the experiment. Ovariectomy and knee arthroplasty were performed. Then, the rats were randomly divided into DFO and control group(n=40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction(PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF and CD31. After 12 weeks, the specimens were examined by micro CT, biomechanics and histopathology to evaluate osteogenesis and osseointegration.

Results: The results of PCR showed mRNA levels of VEGF and CD31 in DFO group were significantly higher than those in control group. The immunohistochemistry results indicated positive cell expressions of HIF-1a, VEGF and CD31 in DFO group were also higher. Compared to control group, the microCT parameters of BMD, BV/TV, TB.N, TB.Th were significantly higher. The maximal pull-out force and the bone-to-implant contact (BIC) value were also higher .

Conclusions: The local administration of DFO which is used to activate HIF-1a signaling pathway can promote osteogenesis and osseointegration with the prosthesis in osteoporotic bone.

Three-dimensional-printed individualized porous implants: A new “implant-bone” interface fusion concept for large bone defect treatment

AUTHORS

Teng Zhang, Qingguang Wei, Hua Zhou, Zehao Jing, Xiaoguang Liu, Yufeng Zheng, Hong Cai, Feng Wei, Liang Jiang, Miao Yu, Yan Cheng, Daoyang Fan, Wenhao Zhou, Xinhong Lin, Huijie Leng, Jian Li, Xinyu Li, Caimei Wang, Yun Tian, Zhongjun Liu

ABSTRACT

Bone defect repairs are based on bone graft fusion or replacement. Current large bone defect treatments are inadequate and lack of reliable technology. Therefore, we aimed to investigate a simple technique using three-dimensional (3D)-printed individualized porous implants without any bone grafts, osteoinductive agents, or surface biofunctionalization to treat large bone defects, and systematically study its long-term therapeutic effects and osseointegration characteristics. Twenty-six patients with large bone defects caused by tumor, infection, or trauma received treatment with individualized porous implants; among them, three typical cases underwent a detailed study. Additionally, a large segmental femur defect sheep model was used to study the osseointegration characteristics. Immediate and long-term biomechanical stability was achieved, and the animal study revealed that the bone grew into the pores with gradual remodeling, resulting in a long-term mechanically stable implant-bone complex. Advantages of 3D-printed microporous implants for the repair of bone defects included 1) that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility, and 2) that osseointegration between the host bone and implants was achieved without bone grafting. Our osseointegration method, in which the “implant-bone” interface fusion concept was used instead of “bone-bone” fusion, subverts the traditional idea of osseointegration.