Preliminary Study on Immediate Postoperative CT Images and Values of the Modular Polyetheretherketone Based Total Knee Arthroplasty: An Observational First-in-Human Trial.

BACKGROUND: Total knee arthroplasty (TKA) is now frequently performed and is highly successful. However, patient satisfaction after TKA is often difficult to achieve. Because of the presence of metallic prosthetic knee joints, there is a lack of imaging tools that can accurately assess the patient's postoperative prosthetic position, soft tissue impingement, and periprosthetic bone density after TKA. We conducted a clinical trial of the world's first totally modular polyetheretherketone (PEEK) TKA and determined the bone density values in the stress concentration area around the prosthesis based on postoperative computed tomography data to reconstruct a three-dimensional model of the PEEK prosthetic knee joint after implantation. Based on the model, the overhang of the prosthesis was measured at various locations on the prosthesis. METHODS: All patients who underwent PEEK-based TKA were postoperatively assessed with radiography and computed tomography (CT). Hounsfield units (HUs) for the different components of the quantitative CT assessment were measured separately. RESULTS: Ten patients (nine female and one male) aged 59-74 (mean 66.9, median 67) years were included. The HU values were as follows: PEEK prosthesis mean 182.95, standard deviation (SD) 4.90, coefficient of variation (CV) 2.68; polyethylene mean -89.41, SD 4.14, CV -4.63; lateral femoral osteochondral mean 192.19, SD 55.05, CV 28.64; lateral tibial osteochondral mean 122.94, SD 62.14, CV 42.86; medial femoral osteophyte mean 180.76, SD 43.48, CV 24.05; and medial tibial osteophyte mean 282.59, SD 69.28, CV 24.52. Analysis of the data at 1, 3, and 6 months showed that the mean PE (p = 0.598) and PEEK (p = 0.916) measurements did not change with the time of measurement. There was a decrease in bone mineral density in the lateral tibia at 3 months (p = 0.044). Otherwise, there was no significant change in bone density in other regions (p = 0.124-0.803). There was no overhang in all femoral prostheses, whereas there were two cases of overhang in tibial prostheses. Overhang measurements do not differ significantly across time points. The overhang measurements were not significantly different at all time points (p = 0.186-0.967). CONCLUSION: PEEK knee joint prosthesis has excellent CT compatibility. The change in periprosthetic bone volume during the follow-up period can be determined using the HU value after CT scan, while the prosthesis position can be assessed. This assessment may potentially guide future improvements in knee prosthesis alignment techniques and artificial knee prosthesis designs.

Hydrofluoric acid and nitric acid cotreatment for biofunctionalization of polyetheretherketone in M2 macrophage polarization and osteogenesis.

Due to its excellent mechanical and low-friction properties, polyetheretherketone (PEEK) has been widely investigated for use in orthopedic applications over the past decade. However, the bioinertness and poor osteogenic properties of PEEK have hampered its clinical application. In this study, the surface of PEEK was modified by co-treatment with hydrofluoric acid and nitric acid (AFN). The microstructures of the modified PEEK surfaces were investigated using scanning electron microscopy. The water contact angles of the surfaces were also measured. To evaluate their cytocompatibility, PEEK samples were used as substrates to culture rat bone mesenchymal stem cells, and cell adhesion, viability, and expression of specific marker genes were measured. Treatment of PEEK with AFN (PEEK-AFN) was found to enable better osteoblast adhesion, spreading, and proliferation; the activity of alkaline phosphatase (an early osteogenic differentiation marker) was also found to be enhanced post-treatment. Furthermore, PEEK-AFN was able to modulate macrophage polarization and down regulated the expression of proinflammatory factors via inhibiting the NF-κB pathway. Thus, treatment of PEEK with AFN could promote M2 polarization of the macrophages and stimulate the differentiation of osteoblasts. These results provide valuable information that could facilitate the use of PEEK-based composites as bone implant materials.

Curcumin Attenuation of Wear Particle-Induced Osteolysis via RANKL Signaling Pathway Suppression in Mouse Calvarial Model.

Wear particle-induced chronic inflammation and osteoclastogenesis are two critical factors in the osteolytic process. Curcumin (CUR) is an active compound of the medicinal herb Curcuma longa and has anti-inflammatory and antiosteoclastogenic properties. Our study tested the hypothesis that CUR might attenuate polymethylmethacrylate- (PMMA-) induced inflammatory osteolysis using mouse calvaria osteolysis model in vivo and in vitro. The mice were divided into four groups: phosphate-buffered saline group, CUR, PMMA, and PMMA + CUR groups. Three days before PMMA particle implantation, the mice were intraperitoneally injected with CUR (25 mg/kg/day). Ten days after the operation, the mouse calvaria was harvested for microcomputed tomography, histomorphometry, and molecular biology analysis. As expected, CUR markedly reduced the secretion of tumor necrosis factor-α, interleukin- (IL-) 1ß, and IL-6 in the calvarial organ culture. Moreover, CUR suppressed osteoclastogenesis and decreased bone resorption in vivo compared with PMMA-stimulated calvaria. Furthermore, CUR downregulated the osteoclast-specific gene expression and reversed the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin messenger RNA and protein ratio in PMMA particle-stimulated mice. These results suggest that CUR attenuated PMMA particle-induced inflammatory osteolysis by suppressing the RANKL signaling pathway in the murine calvarium, which could be a candidate compound to prevent and treat AL.

Curcumin Attenuates Titanium Particle-Induced Inflammation by Regulating Macrophage Polarization In Vitro and In Vivo.

Periprosthetic inflammatory osteolysis and subsequent aseptic loosening are commonly observed in total joint arthroplasty. Other than revision surgery, few approved treatments are available for this complication. Wear particle-induced inflammation and macrophage polarization state play critical roles in periprosthetic osteolysis. We investigated the effects of curcumin, a polyphenol extracted from Curcuma longa, on titanium (Ti) particle-induced inflammation and macrophage polarization in vitro using the murine cell line RAW 264.7 and in vivo using a murine air pouch model. The expression of specific macrophage markers was qualitatively analyzed by immunofluorescence (inducible nitric oxide synthase and CD206) and quantitatively analyzed by flow cytometry (CCR7 and CD206), representing M1 and M2 macrophages, respectively. Our results show that curcumin induced a higher percentage of M2 macrophages together with a higher concentration of anti-inflammatory cytokine IL-10, and a lower percentage of M1 macrophages with a lower concentration of pro-inflammatory cytokines (TNF-α and IL-6). The genes encoding CD86 (M1) and CD163 (M2), two additional markers, were shifted by curcumin toward an M2 phenotype. C57BL/J6 mice were injected with air and Ti particles to establish an air pouch model. Curcumin reduced cell infiltration in the pouch membrane and decreased membrane thickness. The analysis of exudates obtained from pouches demonstrated that the effects of curcumin on macrophage polarization and cytokine production were similar to those observed in vitro. These results prove that curcumin suppresses Ti particle-induced inflammation by regulating macrophage polarization. Thus, curcumin could be developed as a new therapeutic candidate for the prevention and treatment of inflammatory osteolysis and aseptic loosening.

Anthocyanin suppresses CoCrMo particle-induced osteolysis by inhibiting IKKα/ß mediated NF-κB signaling in a mouse calvarial model.

Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model. One hundred and twelve male BALB/c mice were divided randomly into four groups: sham group (sham operation and injection with PBS), vehicle group (CoCrMo particle treatment and injection with PBS), low-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.1mg/g/day), and high-dose anthocyanin group (CoCrMo particle treatment and injecting anthocyanin with 0.4mg/g/day). Mice were sacrificed after two weeks, harvesting the calvariae tissue for in depth analysis by micro-CT, histomorphometry, immunohistochemical and molecular biology analysis. As expected, anthocyanin markedly inhibited CoCrMo particle-induced inflammatory infiltration and decreased bone loss in vivo. Anthocyanin also reversed the increase in the ratio of receptor activator of nuclear factor kappa B ligand (RANKL)/osteoproteger (OPG) and suppressed osteoclast formation in CoCrMo particle-stimulated calvaria. Additionally, anthocyanin significantly reduced the expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the calvaria of CoCrMo-stimulated mice. Furthermore, we confirmed that anthocyanin attenuated osteolysis by blocking NF-κB pathway via inhibiting inhibitor of nuclear factor kappa-B kinase α/ß (IKKα/ß) phosphorylation. In conclusion, our study demonstrated that anthocyanin can protect against CoCrMo particle-induced inflammatory osteolysis via inhibiting the IKKα/ß-NF-κB pathway, and have a potential therapeutic effect on the treatment of wear particle-induced osteolysis.

In vitro and in vivo responses of macrophages to magnesium-doped titanium.

Modulating immune response to biomaterials through changing macrophage polarization has been proven to be a promising strategy to elicit beneficial outcomes in tissue repair. The objective of this study was to evaluate the response of macrophage polarization to titanium doped with magnesium (0.1~0.35%), which was prepared through the magnesium plasma immersion ion implantation (Mg PIII) technique. The M1/M2 polarization profile of macrophages was investigated using a murine cell line RAW 264.7 in vitro and a murine air pouch model in vivo. Our results demonstrated that the Mg PIII-treated titanium induced a higher percentage of M2 macrophages and higher concentrations of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. Genes encoding two growth factors, bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF) were up-regulated, thus indicating the ability of the M2 phenotype to promote wound healing. The nuclear factor κB (NF-κB) signalling pathway was down-regulated. In vivo the Mg PIII -treated titanium elicited a similar effect on macrophage polarization and induced thinner fibrous capsule formation and a decrease in infiltrated cells. These results indicate that Mg PIII treatment has the immunomodulatory potential to elicit the pro-healing M2-polarized macrophage phenotype, thus providing new insight into the development of immunomodulatory biomaterials.

Increased Effects of Extracorporeal Shock Waves Combined with Gentamicin against Staphylococcus aureus Biofilms In Vitro and In Vivo.

An implant-associated bacterial infection is one of the most common and costly complications of orthopedic surgery. Once biofilms develop, it is extremely difficult to cure infections with antimicrobial agents. High-energy extracorporeal shock wave (ESW) treatment has been used for orthopedic-related diseases and has been found to be an effective bactericidal agent that is tolerable both in vitro and in vivo. The broad-spectrum antibiotic gentamicin exhibits bactericidal activity against Staphylococcus aureus, and bacterial resistance to gentamicin is lower. We tested the effectiveness of gentamicin in combination with ESW treatment against S. aureus biofilms in vivo and in vitro. The spread plate method, crystal violet staining, confocal laser scanning microscopy, scanning electron microscopy and microbiologic evaluation were used to compare the effects of combined treatment with those of either treatment alone. The results revealed statistically significant differences between the group treated with ESWs combined with gentamicin and all other groups. Our findings indicate that use of the combination of ESWs with gentamicin is more effective against S. aureus biofilms in vitro and in vivo.

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.

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.

Zn/Ag micro-galvanic couples formed on titanium and osseointegration effects in the presence of S. aureus.

Titanium implants possessing simultaneous osseointegration and antibacterial ability are desirable. In this work, three types of Zn/Ag micro-galvanic couples are fabricated on titanium by plasma immersion ion implantation to investigate the osseointegration and antibacterial effects as well as the involved mechanisms. The in vitro findings disclose enhanced proliferation, osteogenic differentiation, and gene expressions of the rat bone mesenchymal stem cells (rBMSCs), as well as good antibacterial ability on all three micro-galvanic couples. Excellent antimicrobial ability is also observed in vivo and the micro-CT and histological results reveal notable osseointegration in vivo despite the presence of bacteria. The Zn/Ag micro-galvanic couple formed on Zn/Ag dual-ion co-implanted titanium shows the best osseointegration as well as good antibacterial properties in vivo obtained from a rabbit tibia model. The difference among the three Zn/Ag micro-galvanic couples can be ascribed to the contact between the Ag NPs and Zn film, which affects the corrosion process. Our results indicate that the biological behavior can be controlled by the corrosion process of the Zn/Ag micro-galvanic couples.

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.

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.

In vitro and in vivo anti-biofilm effects of silver nanoparticles immobilized on titanium.

Prevention of periprosthetic infection (PPI) by inhibiting biofilm formation on prostheses is crucial to orthopedic surgery. In this work, silver nanoparticles (Ag NPs) are fabricated in situ and immobilized on titanium by silver plasma immersion ion implantation (PIII). The anti-biofilm activity rendered by the immobilized Ag NPs is assessed using Staphylococcus epidermidis, a biofilm producing strain, in vitro and in vivo. The immobilized Ag NPs show no apparent cytotoxicity but reduce biofilm formation in vitro by inhibiting bacteria adhesion and icaAD transcription. The immobilized Ag NPs offer a good defense against multiple cycles of bacteria attack in vitro, and the mechanism is independent of silver release. Radiographic assessment, microbiological cultures, and histopathological results demonstrate the ability of the functionalized surface against bacterial infection to reduce the risk of implant-associated PPI.

Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and antibacterial ability of titanium.

Zinc (Zn) and silver (Ag) are co-implanted into titanium by plasma immersion ion implantation. A Zn containing film with Ag nanoparticles (Ag NPs) possessing a wide size distribution is formed on the surface and the corrosion resistance is improved due to the micro-galvanic couples formed by the implanted Zn and Ag. Not only are the initial adhesion, spreading, proliferation and osteogenic differentiation of rBMSCs observed from the Zn/Ag implanted Ti in vitro, but also bacteria killing is achieved both in vitro and in vivo. Electrochemical polarization and ion release measurements suggest that the excellent osteogenic activity and antibacterial ability of the Zn/Ag co-implanted titanium are related to the synergistic effect resulting from the long-range interactions of the released Zn ions and short-range interactions of the embedded Ag NPs. The Zn/Ag co-implanted titanium offers both excellent osteogenic activity and antibacterial ability and has large potential in orthopedic and dental implants.

[Measurement of proximal femoral morphology and analysis of 500 cases in Hunan Province].

OBJECTIVE: To evaluate the effect of age and gender on the femoral morphology to guide prosthesis selection in operation and design. METHODS: A total of 500 females and males were collected from the departments of orthopedics and medical radiology, Second Xiangya Hospital, Central South University. Informed consent was obtained from all subjects. All patients underwent anteroposterior position scan of the left or right hip joint using Philips Digital Diagnost DR system. The shooting range included the hip joint and at least 2/3 of the proximal femur. The images were measured with Onis 2.3 software. We measured 13 parameters from the patients, including the external parameters of the femur, radius-length parameters of femoral medullary cavity, and morphological parameters of the femoral medullary cavity. RESULTS: Compared with Westeners, the offset was smaller, while the neck shaft angle was significantly larger in Chinese population (P<0.05). Most parameters of the proximal femoral medullary cavity diameter were significantly smaller in Chinese population than those in Westerners (P<0.05). The canal flare index in Chinese population was significantly larger than that in the Westerners (P<0.01). According to the Noble classification, in Chinese population, the proportion of champagne flute type was significantly larger, while the proportion of standard type was significantly smaller than that in Westerners. There was significant difference in the proximal femur between Chinese population and Westerners. The largest difference of the proximal morphology was presented between males and females in the 31-50 years old people (P<0.05), while the smallest was in the over 70 years old population (P>0.05). The main differences between 31 and 70 years old were the diameter of femoral head, the offset of isthmus, the medullary cavity diameter and extracortical width at isthmus level and the medullary cavity diameter at the level of the lesser trochanter (P<0.05). The modullary transverse diameter at 20 mm below the lesser trochanter and isthmus and extracortical width of isthmus in the male and female group was positively correlated with age (P<0.01), while the parameters of the proximal femoral canal morphology in the female group were negatively correlated with age. The female canal parameters had a stronger correlation. CONCLUSION: Chinese proximal femoral parameters are significantly different from Westerners. When people, especially females, get older, the medullary cavity diameter of the isthmus and proximal femur becomes wider and the morphology of the femur becomes straight. The difference in the femoral morphology between the male and female decline with the age. There is almost no difference for the over 70 years old. For the 31-70 years old, The male femoral cavity diameter is larger and the position of isthmus is lower than in the females.