Confirmation of Safety of Titanium Wire in Sternotomy Closure, A Randomized Prospective Study.

BACKGROUND: There are many factors that are known to increase the risk of sternal wound infection (SWI); some studies have reported that nickel is a risk factor for SWI. Titanium wires have only been used as an alternative to steel wires in patients with known allergy to nickel. However, there is a paucity of literature regarding the safety of using titanium wires compared to that on the safety of steel wires for sternum closure after cardiac surgery. Therefore, this study aimed to demonstrate the noninferiority of titanium wires, even in patients without a known allergy. METHODS: A total of 322 patients who underwent elective full median sternotomy were randomly assigned to sternal closure either by titanium wires (n = 161) or by stainless steel wires. RESULTS: Fourteen patients had sternal instability, six (3.7%) patients in the titanium group and eight (5%) patients in the stainless steel group (p = 0.585). There was no statistically significant difference between both groups in terms of postoperative wound infection (p = 0.147). Patients in the titanium group experienced statistically significant lower postoperative pain than those in the stainless steel group (p = 0.024). The wire type was not an independent risk factor for SI, as shown by univariate and logistic regression analyses. CONCLUSION: Titanium wires are a good alternative and have been proven to be safe and effective for sternal closure. The surgeon should be aware of the possibility of developing an allergic reaction to the wires, especially in patients with previous multiple allergic histories.

The contribution of metal allergy to the failure of metal alloy implants, with special reference to titanium: Current knowledge and controversies.

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable.

Oral Exposure to Titanium Dioxide E171 and Zinc Oxide Nanoparticles Induces Multi-Organ Damage in Rats: Role of Ceramide.

Food-grade titanium dioxide (E171) and zinc oxide nanoparticles (ZnO NPs) are common food additives for human consumption. We examined multi-organ toxicity of both compounds on Wistar rats orally exposed for 90 days. Rats were divided into three groups: (1) control (saline solution), (2) E171-exposed, and (3) ZnO NPs-exposed. Histological examination was performed with hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Ceramide (Cer), 3-nitrotyrosine (NT), and lysosome-associated membrane protein 2 (LAMP-2) were detected by immunofluorescence. Relevant histological changes were observed: disorganization, inflammatory cell infiltration, and mitochondrial damage. Increased levels of Cer, NT, and LAMP-2 were observed in the liver, kidney, and brain of E171- and ZnO NPs-exposed rats, and in rat hearts exposed to ZnO NPs. E171 up-regulated Cer and NT levels in the aorta and heart, while ZnO NPs up-regulated them in the aorta. Both NPs increased LAMP-2 expression in the intestine. In conclusion, chronic oral exposure to metallic NPs causes multi-organ injury, reflecting how these food additives pose a threat to human health. Our results suggest how complex interplay between ROS, Cer, LAMP-2, and NT may modulate organ function during NP damage.

[Establishment of Nano-ITO induced rat model of indium lung disease and exploration of its pathological characteristics].

Objective: To study the dynamic pathological characteristics of lung tissue in a Nano-ITO induced rat model of indium lung disease and to guide clinical and basic scientific research to further explore the mechanisms of pulmonary interstitial injury and pulmonary alveolar proteinosis (PAP). Methods: Dose-response (three divided doses) and time-course studies (six exposure periods) were performed to investigate the pulmonary toxicity induced by Nano-ITO. At the end of the experiment, cytokine levels and oxidative stress were analyzed in the bronchoalveolar lavage fluid. Rat lung tissues were also collected for staining with H&E, PAS, Masson's, Oil Red O, and Sirius Red. Ultrastructure of lung tissue cells was observed by transmission electron microscopy. Expression of IL-1ß, HO-1, SP-A was observed by immunohistochemistry, and the expression of α-SMA was observed by immunofluorescence. Results: Nano-ITO intratracheal instillation caused pulmonary toxicity by inducing acute inflammation at 3 days, granuloma (nodule) formation and collagen hyperplasia at 14 days, and alveolar proteinosis at 56 days post-exposure. Pathological features of lung tissue included typical alveolar exudates, cellular fibrous nodules, enlarged alveolar fat droplet fusion, cholesterol crystal granuloma and pulmonary alveolar proteinosis. The intra-alveolar eosinophilic material (multilamellated, lattice-shaped, and myelin-like structure) showed abnormal lamellar bodies (features of alveolar type Ⅱ epithelial cells) and abundant rough endoplasmic reticulum and mitochondria (features of fibroblasts) on transmission electron microscopy of the lung tissue from rats exposed to Nano-ITO on the 84th day. Cellular pathology revealed that a large amount of amorphous PAS stain-positive substances appear in BALF at 28 days post-exposure, and pink granular protein-like substances can be seen in alveolar macrophages. Conclusions: There are three characteristic developmental stages in Nano-ITO induced pulmonary injury in rats, acute inflammation, granuloma (nodule) formation and collagen proliferation, and pulmonary alveolar proteinosis, which provide a reference feature model for the pathogenesis of indium lung disease.

Toxic Metals and Subclinical Atherosclerosis in Carotid, Femoral, and Coronary Vascular Territories: The Aragon Workers Health Study.

OBJECTIVE: Studies evaluating the association of metals with subclinical atherosclerosis are mostly limited to carotid arteries. We assessed individual and joint associations of nonessential metals exposure with subclinical atherosclerosis in 3 vascular territories. Approach and Results: One thousand eight hundred seventy-three Aragon Workers Health Study participants had urinary determinations of inorganic arsenic species, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten. Plaque presence in carotid and femoral arteries was determined by ultrasound. Coronary Agatston calcium score ≥1 was determined by computed tomography scan. Median arsenic, barium, cadmium, chromium, antimony, titanium, uranium, vanadium, and tungsten levels were 1.83, 1.98, 0.27, 1.18, 0.05, 9.8, 0.03, 0.66, and 0.23 µg/g creatinine, respectively. The adjusted odds ratio (95% CI) for subclinical atherosclerosis presence in at least one territory was 1.25 (1.03-1.51) for arsenic, 1.67 (1.22-2.29) for cadmium, and 1.26 (1.04-1.52) for titanium. These associations were driven by arsenic and cadmium in carotid, cadmium and titanium in femoral, and titanium in coronary territories and mostly remained after additional adjustment for the other relevant metals. Titanium, cadmium, and antimony also showed positive associations with alternative definitions of increased coronary calcium. Bayesian Kernel Machine Regression analysis simultaneously evaluating metal associations suggested an interaction between arsenic and the joint cadmium-titanium exposure. CONCLUSIONS: Our results support arsenic and cadmium and identify titanium and potentially antimony as atherosclerosis risk factors. Exposure reduction and mitigation interventions of these metals may decrease cardiovascular risk in individuals without clinical disease.

Suspected allergy to titanium after anterior cervical discectomy and fusion using a Zero-P device: a case report.

PURPOSE: Cases of allergy to large surgical implants have been reported. However, few studies have reported allergy to small titanium-containing implants (e.g. Zero-P device). METHODS: We reported the case of a 51-year old male patient who underwent the anterior cervical discectomy and fusion (ACDF) procedure using a Zero-P device and exhibited allergic symptoms 1 month after the surgery. RESULTS: The allergic symptoms included intermittent tingling and itches in the throat induced by speaking. Systemic rashes over the skin surface and congestion of the eyeball, and dysphagia were also present. Anti-allergic treatment did not resolve the symptoms. Patch tests revealed negative reactions to the rested reagents including titanium. Radiographic results showed solid bone fusion and no signs of chronic inflammation or hypotoxic infection in the surrounding tissues. Upon the patient's request, we removed the titanium screws and plate of the Zero-P device. No allergic reactions were observed after the surgery and at a 6-month follow-up. CONCLUSIONS: Even with a small implant such as the Zero-P device, allergy to titanium may still occur. This case demonstrated the need to screen for the presence of allergy to metals including titanium before the surgery.

Titanium Particles Modulate Lymphocyte and Macrophage Polarization in Peri-Implant Gingival Tissues.

Titanium dental implants are one of the modalities to replace missing teeth. The release of titanium particles from the implant's surface may modulate the immune cells, resulting in implant failure. However, little is known about the immune microenvironment that plays a role in peri-implant inflammation as a consequence of titanium particles. In this study, the peri-implant gingival tissues were collected from patients with failed implants, successful implants and no implants, and then a whole transcriptome analysis was performed. The gene set enrichment analysis confirmed that macrophage M1/M2 polarization and lymphocyte proliferation were differentially expressed between the study groups. The functional clustering and pathway analysis of the differentially expressed genes between the failed implants and successful implants versus no implants revealed that the immune response pathways were the most common in both comparisons, implying the critical role of infiltrating immune cells in the peri-implant tissues. The H&E and IHC staining confirmed the presence of titanium particles and immune cells in the tissue samples, with an increase in the infiltration of lymphocytes and macrophages in the failed implant samples. The in vitro validation showed a significant increase in the level of IL-1ß, IL-8 and IL-18 expression by macrophages. Our findings showed evidence that titanium particles modulate lymphocyte and macrophage polarization in peri-implant gingival tissues, which can help in the understanding of the imbalance in osteoblast-osteoclast activity and failure of dental implant osseointegration.

Type IV Titanium Hypersensitivity: Rare, or Rarely Detected?

The presented review aims to summarize the current knowledge of hypersensitivity to titanium - a material widely used in medical applications thanks to its exceptional chemical stability, resistance to corrosion, low specific weight and high strength. The hypersensitivity to metals is usually caused by the Type IV immunopathological reaction. Case reports on allergic reactions to titanium are rare but the actual occurrence can be expected to be much higher, especially due to its problematic detection. Although cutaneous patch tests are widely accepted and used for the diagnosis of hypersensitivity of numerous metals (e.g. Ni), it is notoriously unreliable in case of allergies to titanium, which may be associated with the low percutaneous transport of titanium and its salts. The Lymphocyte Transformation Test has superior sensitivity but it remains mostly unknown among clinicians and there are not many laboratories capable of performing it. This review presents numerous case reports indicating, in combination with the above-mentioned facts, that hypersensitivity to titanium should be considered as a possible cause also in non-specific problems associated with titanium implant failure. Key words: titanium, allergy, patch test, lymphocyte transformation test.

Metal hypersensitivity and pro-inflammatory cytokine production in patients with failed orthopedic implants: A case-control study.

Orthopedic implants heal well without complications in most patients but fail for unclear reasons in some individuals. This study determined the relevance of metal hypersensitivity in patients with failed orthopedic implants and those requiring orthopedic implant surgery. The study included 35 patients with failed orthopedic implants and 15 subjects scheduled for orthopedic implant surgery. The production of selected pro-inflammatory cytokines was measured in patients with failed orthopedic implants. Metal hypersensitivity was measured in all subjects using the MELISA® test. Of common metals in orthopedic alloys, the patients with failed orthopedic implants responded most frequently to nickel, chromium, titanium, iron, and molybdenum. Hypersensitivity to metals found in implants was measured in 40% of patients with failed implants. The study also showed that titanium exposure in patients with titanium hypersensitivity might lead to implant failure. Metal hypersensitivity testing should be offered to patients before surgery to minimize the risk of implant failure.

LY450139 Inhibited Ti-Particle-Induced Bone Dissolution via Suppressing Notch and NF-κB Signaling Pathways.

Aseptic loosening of the prosthesis caused by wear-particle-induced osteolysis is a long-term complication and one of the most common reasons for the failure of joint implants. The primary cause of aseptic loosening of the prosthesis is overactive bone resorption caused by wear-particle-activated osteoclasts in both direct and indirect ways. Therefore, drugs that can inhibit differentiation and bone resorption of osteoclasts need investigation as a potential therapeutic strategy to prevent and treat peri-prosthetic osteolysis and thereby prolong the service life of the prosthesis. This study has verified the potential inhibitory effect of LY450139 on inflammatory osteolysis induced by titanium particles in a mice skull model. In addition, we found that LY450139 inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis, bone resorption, and podosomal actin belt formation in a dose-dependent manner without evidence of cytotoxicity in vitro. In addition, LY450139 significantly decreased the expression of osteoclast-specific markers, including TRAP, CTSK, V-ATPase d2, CTR, DC-STAMP, NFATc1, and the downstream target gene Hes1 in Notch signaling pathway. Further investigation of the molecular mechanism demonstrated that LY450139 inhibited the formation of osteoclasts via inhibition of the NF-κB and Notch signaling pathways. In summary, LY450139 inhibited the formation of RANKL-mediated osteoclasts via NF-κB and Notch signaling and inhibited Ti particle-induced inflammatory osteolysis in vivo. LY450139 is a potential targeted drug for the treatment of peri-prosthetic osteolysis and other osteolytic disease associated with overactive osteoclasts.

The role of foreign body response in peri-implantitis: What is the evidence?

Historically, there has been broad consensus that osseointegration represents a homeostasis between a titanium dental implant and the surrounding bone, and that the crestal bone loss characteristic of peri-implantitis is a plaque-induced inflammatory process. However, this notion has been challenged over the past decade by proponents of a theory that considers osseointegration an inflammatory process characterized by a foreign body reaction and peri-implant bone loss as an exacerbation of this inflammatory response. A key difference in these two schools of thought is the perception of the relative importance of dental plaque in the pathogenesis of crestal bone loss around implants, with obvious implications for treatment. This review investigates the evidence for a persistent foreign body reaction at osseointegrated dental implants and its possible role in crestal bone loss characteristic of peri-implantitis. Further, the role of implant-related material release within the surrounding tissue, particularly titanium particles and corrosion by-products, in the establishment and progression in peri-implantitis is explored. While it is acknowledged that these issues require further investigation, the available evidence suggests that osseointegration is a state of homeostasis between the titanium implant and surrounding tissues, with little evidence that a persistent foreign body reaction is responsible for peri-implant bone loss after osseointegration is established. Further, there is a lack of evidence for a unidirectional causative role of corrosion by-products and titanium particles as possible non-plaque related factors in the etiology of peri-implantitis.

Gestational exposure to titanium dioxide, diesel exhaust, and concentrated urban air particles affects levels of specialized pro-resolving mediators in response to allergen in asthma-susceptible neonate lungs.

Maternal gestational exposures to traffic and urban air pollutant particulates have been linked to increased risk and/or worsening asthma in children; however, mechanisms underlying this vertical transmission are not entirely understood. It was postulated that gestational particle exposure might affect the ability to elicit specialized proresolving mediator (SPM) responses upon allergen encounter in neonates. Lipidomic profiling of 50 SPMs was performed in lungs of neonates born to mice exposed to concentrated urban air particles (CAP), diesel exhaust particles (DEP), or less immunotoxic titanium dioxide particles (TiO2). While asthma-like phenotypes were induced with identical eosinophilia intensity across neonates of all particle-exposed mothers, levels of LXA4, HEPE and HETE isoforms, and HDoHe were only decreased by CAP and DEP only but not by TiO2. However, RvE2 and RvD1 were inhibited by all particles. In contrast, isomers of Maresin1 and Protectin D1 were variably elevated by CAP and DEP, whereas Protectin DX, PGE2, and TxB2 were increased in all groups. Only Protectin D1/DX, MaR1(n-3,DPA), 5(S),15(S)-DiHETE, PGE2, and RvE3 correlated with eosinophilia but the majority of other analytes, elevated or inhibited, showed no marked correlation with inflammation intensity. Evidence indicates that gestational particle exposure leads to both particle-specific and nonspecific effects on the SPM network.

Titanium dental implant-related pathologies: A retrospective histopathological study.

OBJECTIVES: To perform a retrospective, descriptive, histopathological study of peri-implant tissue pathologies associated with titanium dental implants (TDI), and to evaluate the presence of metallic particles in samples from a single diagnostic center. METHODS: Sixty-eight cases of TDI-associated lesions were retrieved from the Surgical Pathology Laboratory archives, School of Dentistry, University of Buenos Aires (UBA) (1990-2018). The study included re-examining the histopathological features of the biopsy samples, analyzing the inflammatory infiltrate, and examining the samples to detect metallic particles whose chemical composition was determined spectrophotometrically (EDS). Available clinical and radiographic data were also reviewed. RESULTS: The retrieved cases ranged from lesions of inflammatory origin to neoplastic lesions. Metallic particles were observed in 36 cases (52.9%), all of which showed inflammation. Particle length ranged from 2 to 85µm. EDS analysis of the particles/deposits observed in the tissues showed the presence of aluminum, titanium, iron, and nickel, among other elements. CONCLUSIONS: A significant number of TDI-associated lesions, including cases not reported to date and diagnosed at a single diagnostic center, are shown here. Cases showing particles exhibited an inflammatory response, irrespective of the histopathological diagnosis. The role of metallic particles in the development of TDI-associated lesion is yet to be established.

Blood titanium levels in patients with large and sliding titanium implants.

BACKGROUND: Titanium, which is known to be a highly biologically inert element, is one of the most commonly used metals in orthopaedic implants. While cobalt and chromium blood metal ion testing is routinely used in the clinical monitoring of patients with metal-on-metal hip implants, much less is known about the levels of titanium in patients with other implant types. The aim of this study was to better understand the normal ranges of blood titanium levels in patients implanted with large and sliding titanium constructs by comparison with reference levels from conventional titanium hips. METHODS: This study examined data collected from 136 patients. Over a period of 24 months, whole blood samples were collected from 41 patients implanted with large titanium implants: long (range 15 to 30 cm) spine rods with a sliding mechanism ("spine rods", n = 18), long bone tumour implants ("tumour implants", n = 13) and 3D-printed customised massive acetabular defect implants ("massive acetabular implants", n = 10). This data was compared with standard, uncemented primary titanium hip implants ("standard hips", 15 cm long) (n = 95). Clinical, imaging and blood titanium levels data were collected for all patients and compared statistically between the different groups. RESULTS: The median (range) of blood titanium levels of the standard hip, spine rods, femoral tumour implants and massive acetabular implants were 1.2 ppb (0.6-4.9), 9.7 ppb (4.0-25.4), 2.6 ppb (0.4-104.4) and 5.7 ppb (1.6-31.5) respectively. Spine rods and massive acetabular implants had significantly greater blood titanium levels compared to the standard hips group (p < 0.001). CONCLUSION: This study showed that titanium orthopaedic implants that are large and/or have a sliding mechanism have higher blood titanium levels compared to well-functioning, conventionally sized titanium hips. Reassuringly, the increased levels did not appear to induce adverse metal reactions. This study provides useful baseline data for future studies aimed at assessing blood titanium levels as a biomarker for implant function.

In vivo biocompatibility evaluation of 3D-printed nickel-titanium fabricated by selective laser melting.

Nickel-titanium (NiTi) belongs to the group of shape-memory alloys (SMAs), which are characterized by flexibility and reversible deformability. Advanced techniques in 3D printing by selective laser-melting (SLM) process allow the manufacturing of complex patient-specific implants from SMAs. Osteosynthesis materials made of NiTi could be used for minimally invasive surgical approaches in oral- and maxillofacial surgery. However, the in vivo biocompatibility has not yet been fully investigated, especially in load-sharing and load-bearing implants. The aim of this study was to evaluate the in vivo biocompatibility of SLM-produced NiTi for intraosseous and subperiosteal applications. Test specimens were implanted into the frontonasal bone of ten miniature pigs. To assess peri-implant bone metabolism, fluorescent dye was administered after 2, 4, 6, 10, 12, and 14 weeks intraperitoneally. Specimens and the surrounding tissues were harvested after 8 and 16 weeks for histological analysis. While the NiTi implants presented a higher bone-to-implant contact ratio (BIC) after 8 than after 16 weeks (43.3 vs. 40.3%), the titanium implants had a significantly higher BIC after 16 weeks (33.6 vs. 67.7%). Histologically, no signs of peri-implant inflammation or foreign-body reaction were detectable. With respect to this preliminary study design, 3D-printed NiTi shows sufficient biocompatibility for intraosseous and subperiosteal implant placement.

[A non-targeted metabolomics study on serum of occupational people exposed with nanometer titanium dioxide particles (TiO(2)-NPs)].

Objective: To study the changes of serum metabolic profile of occupational people exposed with nanometer titanium dioxide particles (TiO(2)-NPs), and to explore the biomarkers and injury mechanism of TiO(2)-NPs health effects. Methods: From June 2020 to June 2021, a TiO(2)-NPs production enterprise was selected as the research site by a typical sampling method, 64 people in the TiO(2)-NPs exposure group were selected from the enterprise, and 62 people of the logistics administrative staff in the same enterprise were selected as the control group, and blood samples were collected using non-anticoagulant blood collection tubes. After the samples were methanol-precipitated, the untargeted metabolomic data was collected by ultra-high performance liquid chromatography time-of-flight mass spectrometry, and biomarkers were screened and metabolic pathway analysis was performed. Results: 46 different metabolites were screened out by P<0.05 and variable importance projection index (VIP) value >1, mainly including glycerides, sphingomyelin, glycerophospholipid, fatty acyl, etc.; By ROC analysis to determine 3-hydroxy-4, 5-dimethyl-2 (5H) - furanone, 4-aminobiphenyl, heptanoylcarnitine, Hexadecanedioic acid mono-L-carnitine ester, Ibutilide, LysoPA (18∶1 (9Z) /0∶0), LysoPC (18∶0), PC (16∶0/16∶0), PC (16∶0/20: 4 (5Z, 8Z, 11Z, 14Z) ), PC (P-18∶1 (9Z) /P-18∶1 (9Z) ) 10 candidate biomarkers; involving changes in 4 metabolic pathways, namely glycerophospholipid metabolism, sphingolipid metabolism, phenylalanine, tyrosine and tryptophan acid biosynthesis, linoleic acid metabolism. Conclusion: Occupational exposure to TiO(2)-NPs has a significant impact on serum metabolic profiles.

Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis.

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has anti-inflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

Combined Endothelialization Promoting and Surface Binding Chimeric Conjugate with Low Thrombogenicity.

Endothelialization of blood contacting implants, e.g., vascular stents, is regarded as a prerequisite for an improved performance in terms of minimizing thrombogenicity and the inhibition of restenosis. Commonly used materials, such as Ti-based alloys, can be surface-modified in order to improve endothelial cell (EC) colonization as well as to reduce platelet adhesion. Standard modification techniques involve silanization and are laborious and time-consuming. We propose a novel single-step procedure based on a surface-recognizing peptide generated by phage display methodology. Combining this with a polyethylene glycol (PEG) spacer and an EC-specific sequence yielded a conjugate applicable for the modification of Ti surfaces.

Naringin inhibits titanium particles-induced up-regulation of TNF-α and IL-6 via the p38 MAPK pathway in fibroblasts from hip periprosthetic membrane.

AIMS: Inflammatory responses to wear debris cause osteolysis that leads to aseptic loosening and hip arthroplasty failure. Wear debris stimulate macrophages and fibroblasts to secret proinflammatory cytokines, including TNF-α and IL-6, which have been specifically implicated in periprosthetic osteolysis and osteoclast differentiation. Naringin has anti-inflammatory effect in macrophages. Moreover, naringin inhibited osteoclastogenesis and wear particles-induced osteolysis. In this study, we examined the potential inhibitory effects of naringin on titanium (Ti) particle-induced proinflammatory cytokines secretion in fibroblasts and the possible underlying molecular mechanisms. MATERIALS AND METHODS: Fibroblasts were isolated from periprosthetic membrane at the time of revision surgery performed due to aseptic loosening after hip arthroplasty and were cultured in the presence or absence of Ti particles, naringin and mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (a selective inhibitor of ERK), SP600125 (a selective inhibitor of JNK), and SB203580 (a selective inhibitor of p38). TNF-α and IL-6 assays were performed using enzyme-linked immunosorbent assay kits. The phosphorylation levels of p38 and nuclear factor kappa B p65 (NF-κB p65) were examined by western blot. RESULTS: Naringin or SB203580 pretreatment significantly suppressed the secretion of TNF-α and IL-6 induced by titanium particles in fibroblasts, while inhibition of ERK or JNK pathways showed no effect on production of TNF-α and IL-6. Moreover, naringin inhibited Ti particle-induced phosphorylation of p38 and p65. CONCLUSIONS: These results indicated that naringin could inhibit Ti particle-induced inflammation in fibroblasts by inhibiting p38 MAPK/NF-κB p65 activity and might be a potential drug for the treatment of inflammatory periprosthetic osteolysis after arthroplasty.

Netrin-1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle-induced osteoclastogenesis.

BACKGROUND: Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this study was to investigate the molecular mechanism of osteoclast formation and dissolution induced by wear particles and the potential roles of Netrin-1, the ERK1/2 pathway and autophagy activation in this process. METHODS: The messenger RNA levels in cells and tissues were detected with real-time quantitative PCR. The western blotting was used to detect the expression of proteins. A CCK-8 kit was used to detect the viability of RAW 264.7 cells. Moreover, an air pouch model of bone resorption was established. Immunohistochemistry was used to detect the expression of TRAP and Netrin-1 in rat bone tissue. Cell culture supernatants were collected in the rat air pouch model of bone resorption, and the levels of RANKL and OPG were detected with enzyme-linked immunosorbent assay. The protein levels of TRAP and Netrin-1 in bone tissue were examined by immunohistochemistry. RESULTS: Titanium wear particles induced osteoclast formation and autophagy activation. Moreover, blocking autophagy suppressed the osteoclastogenesis after exposure to wear particles in vitro. The activation of the ERK1/2 pathway and the overexpression of Netrin-1 were both found to play important roles in osteoclastogenesis mediated by autophagy. Moreover, 3-MA effectively decreased the secretion of proinflammatory cytokines mediated by wear particles. CONCLUSION: Blockade of autophagy inhibits the osteoclastogenesis and inflammation induced by wear particles, thus potentially providing novel treatment strategies for abnormal osteoclastogenesis and aseptic prosthesis loosening induced by wear particles.