Guodong Jin

Osteogenic activity and antibacterial effect of zinc ion implanted titanium

Titanium (Ti) and its alloys are widely used as orthopedic and dental implants. In this work, zinc (Zn) was implanted into oxalic acid etched titanium using plasma immersion ion implantation technology. Scanning electron microscopy and X-ray photoelectron spectroscopy were used to investigate the surface morphology and composition of Zn-implanted titanium. The results indicate that the depth profile of zinc in Zn-implanted titanium resembles a Gaussian distribution, and zinc exists in the form of ZnO at the surface whereas in the form of metallic Zn in the interior. The Zn-implanted titanium can significantly stimulate proliferation of osteoblastic MC3T3-E1 cells as well as initial adhesion, spreading activity, ALP activity, collagen secretion and extracellular matrix mineralization of the rat mesenchymal stem cells. The Zn-implanted titanium presents partly antibacterial effect on both Escherichia coli and Staphylococcus aureus. The ability of the Zn-implanted titanium to stimulate cell adhesion, proliferation and differentiation as well as the antibacterial effect on E. coli can be improved by increasing implantation time even to 2 h in this work, indicating that the content of zinc implanted in titanium can easily be controlled within the safe concentration using plasma immersion ion implantation technology. The Zn-implanted titanium with excellent osteogenic activity and partly antibacterial effect can serve as useful candidates for orthopedic and dental implants.

Influence of sulfur content on bone formation and antibacterial ability of sulfonated PEEK

Polyetheretherketone (PEEK) is desirable in orthopedic and dental applications because its mechanical properties are similar to those of natural bones but the bioinertness and inferior osteoconduction of PEEK have hampered many clinical applications. In this work, PEEK is sulfonated by concentrated sulfuric acid to fabricate a three-dimensional (3D) network. A hydrothermal treatment is subsequently conducted to remove the residues and the temperature is adjusted to obtain different sulfur concentrations. In vitro cell proliferation and real-time PCR analyses disclose enhanced proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs) on the samples with small sulfur concentrations. The in vitro antibacterial evaluation reveals that all the sulfonated samples possess excellent resistance against Staphylococcus aureus and Escherichia coli. The in vivo rat femur implantation model is adopted and X-ray, micro-CT, and histological analyses indicate that not only the premeditated injected bacteria cells are sterilized, but also new bone forms around the samples with small sulfur concentrations. The in vitro and in vivo results reveal that the samples subjected to the hydrothermal treatment to remove excess sulfur have better osseointegration and antibacterial ability and PEEK modified by sulfonation and hydrothermal treatment is promising in orthopedic and dental applications.

Antimicrobial and osteogenic properties of silver-ion-implanted stainless steel.

Prevention of implant loosening and infection is crucial to orthopedic and dental surgeries. In this work, the surface of stainless steel (SS) was modified by silver-sourced plasma immersion ion implantation (Ag-PIII). Metallic silver nanoparticles with various diameters and distributions were fabricated on the SS surfaces after treatment with Ag-PIII for 0.5 and 1.5 h, respectively. The osteogenic activity and antimicrobial properties of SS before and after Ag-PIII treatment were evaluated using in vitro and in vivo tests. The results demonstrated that Ag-PIII treatment not only promoted the antibacterial activity of SS but also enhanced the osteogenic differentiation of human bone marrow stromal cells.

Calcium Plasma Implanted Titanium Surface with Hierarchical Microstructure for Improving the Bone Formation

Introducing hierarchical microstructure and bioactive trace elements simultaneously onto the surface of titanium implant is a very effective way to improve the osseointegration between bone and implant. In this work, hierarchical topography was prepared on Ti surface via acid etching and sandblasting (SLA) to form micropits and microcavities then underwent Ca plasma immersion ion implantation (Ca-PIII) process. The surface wettability and roughness did not change obviously before and after Ca-PIII process. The in vitro evaluations including cell adhesion, activity, alkaline phosphatase (ALP), osteogenic genes (Runx2, OSX, ALP, BSP, Col1a1, OPN, and OC), and protein (BSP, Col1a1, OPN, and OC) expressions revealed that the introduction of Ca ions onto the surface of SLA-treated Ti can promote greater osteoblasts adhesion, spread and proliferation, which in return further accelerated the maturation and mineralization of osteoblasts. More importantly, in vivo evaluations including Micro-CT evaluation, histological observations, push-out test, sequential fluorescent labeling and histological observations verified that Ca-SLA-treated Ti implants could efficiently promote new bone formation in early times. These promising results suggest that Ca-SLA-treated Ti has the potential for future application in orthopedic field.

Multifunctions of dual Zn/Mg ion co-implanted titanium on osteogenesis, angiogenesis and bacteria inhibition for dental implants

In order to improve the osseointegration and long-term survival of dental implants, it is urgent to develop a multifunctional titanium surface which would simultaneously have osteogeneic, angiogeneic and antibacterial properties. In this study, a potential dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed via plasma immersion ion implantation (PIII). The Zn/Mg-PIII surfaces were found to promote initial adhesion and spreading of rat bone marrow mesenchymal stem cells (rBMSCs) via the upregulation of the gene expression of integrin α1 and integrin β1. More importantly, it was revealed that Zn/Mg-PIII could increase Zn2+ and Mg2+ concentrations in rBMSCs by promoting the influx of Zn2+ and Mg2+ and inhibiting the outflow of Zn2+, and then could enhance the transcription of Runx2 and the expression of ALP and OCN. Meanwhile, Mg2+ ions from Zn/Mg-PIII increased Mg2+ influx by upregulating the expression of MagT1 transporter in human umbilical vein endothelial cells (HUVECs), and then stimulated the transcription of VEGF and KDR via activation of hypoxia inducing factor (HIF)-1α, thus inducing angiogenesis. In addition to this, it was discovered that zinc in Zn/Mg-PIII had certain inhibitory effects on oral anaerobic bacteria (Pg, Fn and Sm). Finally, the Zn/Mg-PIII implants were implanted in rabbit femurs for 4 and 12weeks with Zn-PIII, Mg-PIII and pure titanium as controls. Micro-CT evaluation, sequential fluorescent labeling, histological analysis and push-out test consistently demonstrated that Zn/Mg-PIII implants exhibit superior capacities for enhancing bone formation, angiogenesis and osseointegration, while consequently increasing the bonding strength at bone-implant interfaces. All these results suggest that due to the multiple functions co-produced by zinc and magnesium, rapid osseointegration and sustained biomechanical stability are enhanced by the novel Zn/Mg-PIII implants, which have the potential application in dental implantation in the future. STATEMENT OF SIGNIFICANCE In order to enhance the rapid osseointegration and long-term survival of dental implants, various works on titanium surface modification have been carried out. However, only improving osteogenic activity of implants is not enough, because angiogenesis and bacteria inhibition are also very important for dental implants. In the present study, a novel dental implant material-dual Zn/Mg ion co-implanted titanium (Zn/Mg-PIII) was developed, which was found to have superior osteoinductivity, pro-angiogenic effects and inhibitory effects against oral anaerobes. Furthermore, synergistic effects of Zn/Mg ions on osteogenic differentiation of rBMSCs and the possible mechanism were discovered. In addition, rapid osseointegration and sustained biomechanical stability are greatly enhanced by Zn/Mg-PIII implants, which may have the potential application in dental implantation in the future. We believe this paper may be of particular interest to the readers.

Balancing the Osteogenic and Antibacterial Properties of Titanium by Codoping of Mg and Ag: An in Vitro and in Vivo Study

To simultaneously enhance the osteogenic and antibacterial properties of titanium, we introduced magnesium (Mg), silver (Ag), or both by using the plasma immersion ion implantation (PIII) technique, producing three PIII sample groups, namely, Mg-doped titanium (Mg-PIII), Ag-doped titanium (Ag-PIII), and Mg and Ag codoped titanium (Mg/Ag-PIII). The in vitro antibacterial efficacy of Mg/Ag-PIII group was about 7-10% higher than that of Ag-PIII. In vitro and in vivo results demonstrated that osteogenic property of Mg/Ag PIII group was better than that of Ag-PIII or Mg-PIII. It was believed that the galvanic effects between Mg and Ag NPs played a key role in facilitating the release of Mg but reducing the release of silver, answering for the selective performances of the Mg/Ag-PIII group over bacterial and mammalian cells. This study demonstrated that the integration of multiple functional elements could be realized by the dual-source PIII technique, and in this case, the antibacterial properties and osteogenic property of titanium could be balanced.

Graphene film-functionalized germanium as a chemically stable, electrically conductive, and biologically active substrate

As a microelectronics material, germanium (Ge) has attracted wide interest for semiconductor devices (like biosensors) since its usage to build the first transistor. In this study, large-area monolayer graphene film was directly in situ deposited on a Ge substrate by the chemical vapor deposition (CVD) method. The aim of this study is to explore whether a graphene overlayer on Ge can influence its surface properties. The quality and homogeneity of the graphene film were investigated by Raman spectroscopy and transmission electron microscopy (TEM). The graphene overlayer was demonstrated to act as a protective layer for Ge to improve its corrosion resistance. Compared to bare Ge, graphene film-modified Ge can up-regulate gene expressions of osteogenic markers of mesenchymal stem cells, confirming the enhanced biological activity. Meanwhile, the graphene film also showed good antibacterial ability presumably due to the charge transfer to extract electrons from the bacterial membrane. We hope this work can provide new insights for surface modification and functionalization of Ge-based biosensors and medical devices to better meet clinical needs. The concept of utilizing graphene as a protective, conductive and bioactive layer might provide a viable alternative convenient for further usage of implantable Ge-based biomedical devices.

Nano-thick calcium oxide armed titanium: boosts bone cells against methicillin-resistant Staphylococcus aureus

Since the use of systemic antibiotics for preventing acute biomaterial-associated infections (BAIs) may build up bacterial resistance and result in huge medical costs and unpredictable mortality, new precaution strategies are required. Here, it demonstrated that titanium armed with a nano-thick calcium oxide layer was effective on averting methicillin-resistant Staphylococcus aureus (MRSA) infections in rabbits. The calcium oxide layer was constructed by, firstly, injecting of metallic calcium into titanium via a plasma immersion ion implantation process, and then transforming the outer most surface into oxide by exposing to the atmosphere. Although the calcium oxide armed titanium had a relative low reduction rate (~74%) in growth of MRSA in vitro, it could markedly promote the osteogenic differentiation of bone marrow stem cells (BMSCs), restore local bone integration against the challenge of MRSA, and decrease the incidence of MRSA infection with a rate of 100% (compared to the titanium control). This study demonstrated for the first time that calcium, as one of the major elements in a human body, could be engineered to avert MRSA infections, which is promising as a safe precaution of disinfection for implantable biomedical devices.

Antibacterial activity, osteogenic and angiogenic behaviors of copper-bearing titanium synthesized by PIII&D

Cu-bearing biomaterials have drawn considerable interest in hard tissue replacement. However, a better compromise between the biocompatibility and cytotoxicity of incorporated copper is still required. In this work, two types of Cu-bearing surfaces were obtained on Ti by altering the processing parameters during PIII&D. One with a certain amount of copper in metallic form on the Ti surface shows enhanced antibacterial ability, osteogenic and angiogenic capabilities, whereas unfavorable biocompatibility is observed from the other Ti surface in the presence of Cu-bearing nanoparticles. Disparate biological differences between two types of Cu-bearing Ti surfaces synthesized by the same single technique provides insights for better understanding of the underlying mechanism between the positive and negative bioeffects of Cu-bearing biomaterials.