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1.
Biotechnol Bioeng ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34596239

RESUMO

The generation of degradation products (DPs) like ions and organo-metallic particles from corroding metallic implants is an important healthcare concern. These DPs generate local and systemic toxicity. The impact on local toxicity is well documented, however, little is known about systemic toxicity. This is mainly due to the limited scope of the current microtiter plate-based (static) toxicity assay techniques. These methods do not mimic the systemic (dynamic) conditions. In this study, it is hypothesized that DPs incubated with cells in static conditions might provide improper systemic toxicity results, as there is no movement mimicking the blood circulation around cells. This study reports the development of a three-chambered prototype microfluidic system connected to the operational hip implant simulator to test the cellular response induced by the DPs. This setup is called a dynamic microfluidic bioreactor-hip simulator system. We hypothesize that a dynamic microfluidic system will provide a realistic toxicology response induced by DPs than a static cell culture plate. To prove the hypothesis, Neuro2a (N2a) cells were used as representative cells to study systemic neurotoxicity by the implant DPs. The microfluidic bioreactor system was validated by comparing the cell toxicity against the traditional static system and using COMSOL modeling for media flow with DPs. The hip implant simulator used in this study was a state-of-the-art sliding hip simulator developed in our lab. The results suggested that static toxicity was significantly more compared to dynamic microfluidic-based toxicity. The newly developed DMBH system tested for in situ systemic toxicity on N2a cells and demonstrated very minimum toxicity level (5.23%) compared to static systems (31.16%). Thus, the new DMBH system is an efficient tool for in situ implant metal systemic toxicity testing.

2.
Am J Dent ; 34(4): 191-194, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34370910

RESUMO

PURPOSE: To evaluate the in vitro protective effect of a mint formulation containing (-)-epigallocatechin-3-gallate (EGCg-mint) on root dentin exposed to a highly erosive environment in the presence and absence of proteolytic challenge. METHODS: Root dentin specimens were subjected to an erosion-remineralization cycling model (6×/day; 5 days) that included 5-minute immersion in 1% citric acid and 60-minute immersion in remineralization solution (RS). At the remineralization half-time, the specimens were treated (n= 20) with EGCg-mint, RS (negative control) or sodium fluoride (1,000 ppm of NaF; positive control). Half of the specimens were kept overnight in RS (pH cycling) and the other half in RS with Clostridium histolyticum collagenase (pH-proteolytic cycling). Erosion depth was measured using optical profilometry and data analyzed by two-way ANOVA and Tukey tests (α= 0.05). RESULTS: Under pH-cycling, NaF resulted in statistically lower erosion depth compared to EGCg-mint (P= 0.020) and RS (P= 0.005). Under pH-proteolytic cycling, EGCg-mint and NaF significantly decreased the tissue loss (erosion depth, P< 0.001) compared to the RS. The EGCg-mint exhibited an anti-erosion property on root dentin under a proteolytic challenge. NaF presented an anti-erosion property regardless of the erosive cycling model. CLINICAL SIGNIFICANCE: The anti-erosive action of an over-the-counter mint, containing active ingredients, including epigallocatechin-3-gallate, is likely by the protective mechanisms of the dentin extracellular matrix.


Assuntos
Mentha , Erosão Dentária , Ácido Cítrico , Dentina , Fluoretos , Humanos , Fluoreto de Sódio/farmacologia , Erosão Dentária/prevenção & controle
3.
J Mech Behav Biomed Mater ; 123: 104769, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34412025

RESUMO

In orthopedic healthcare, Total Hip Replacement (THR) is a common and effective solution to hip-related bone and joint diseases/fracture; however, corrosion of the hip implant and the release of degradation metal ions/particles can lead to early implant failure and pose potential toxicity risk for the surrounding tissues. The main objective of this work was to investigate the potential role of Vitamin E to minimize corrosion-related concerns from CoCrMo hip implants. The study focused on two questions (i) Can Vitamin E inhibit CoCrMo corrosion? and (ii) Does Vitamin E moderate the toxicity associated with the CoCrMo implant particles? In the study (i) the electrochemical experiments (ASTM G61) with different concentrations of Vitamin E (1, 2, 3 mg/ml against the control) were performed using normal saline and simulated synovial fluid (Bovine calf serum-BCS, 30 g/L protein, pH 7.4) as electrolytes. The polished CoCrMo disc (Ra 50 nm) was the working electrode. The findings suggested that both Vitamin E-Saline (45 ± 0.9%) and Vitamin E-BCS (91 ± 3%) solutions protected against implant corrosion at a Vitamin E concentration of 3 mg/ml, but Vitamin E-BCS showed protection at all Vitamin E (1-3 mg/ml) concentration levels. These results suggested that the Vitamin E and the protein present in the BCS imparted additive effects towards the electrochemical inhibition. In the study (ii) the role of Vitamin E in cytotoxicity inhibition was studied using a mouse neuroblastoma cell line (N2a) for CoCrMo particles and Cr ions separately. The CoCrMo particles were generated from a custom-built hip simulator. The alamarBlue assay results suggested that Vitamin E provides significant protection (85% and 75% proliferation) to N2a cells against CoCrMo particles and Cr ions, respectively at 1 µg/ml concentration, as compared to the control group. However, the results obtained from ROS expression and DNA fiber staining suggest that Vitamin E is only effective against CoCrMo degradation particles and not against Cr ions. In summary, the findings show that Vitamin E can minimize the corrosion processes and play a role in minimizing the potential toxicity associated with implants.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Animais , Bovinos , Corrosão , Prótese de Quadril/efeitos adversos , Metais , Vitamina E
4.
Toxicol Lett ; 350: 213-224, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34252509

RESUMO

The metal/metal alloy-based implants and prostheses are in use for over a century, and the rejections, revisions, and metal particle-based toxicities were reported concurrently. Complications developed due to metal ions, metal debris, and organo-metallic particles in orthopedic patients have been a growing concern in recent years. It was reported that local and systemic toxicity caused by such released products from the implants is one of the major reasons for implant rejection and revision. Even though the description of environmental metal toxicants and safety limits for their exposure to humans were well established in the literature, an effort was not adequately performed in the case of implant-based metal toxicology. Since the metal ion concentration in serum acts as a possible indicator of the systemic toxicity, this review summarizes the reported human serum safe limits, toxic limits, and concentration range (µg/L, ppb, etc.) for mild to severe symptoms of six (cardiac, hepatic, neuro, nephron, dermal and endocrine) systemic toxicities for twelve most commonly used metallic implants. It also covers the widely used metal ion quantification techniques and systemic toxicity treatments reported.


Assuntos
Cardiotoxicidade/etiologia , Intoxicação por Metais Pesados/etiologia , Íons/toxicidade , Metais/toxicidade , Próteses e Implantes/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Intoxicação por Metais Pesados/sangue , Humanos , Íons/sangue , Masculino , Metais/sangue , Pessoa de Meia-Idade
5.
Mater Sci Eng C Mater Biol Appl ; 126: 112128, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082945

RESUMO

According to the National Center for Health Statistics, currently, more than 250,000 total hip replacements annually in the US alone, with an estimated increase to 500,000 by the year 2030. The usage of tapered junctions between the femoral neck and head gives the surgeon flexibility in implant assembly. However, these modular junctions are subjected to micro-motion that may cause chemical and fretting-corrosion at the modular junction. Therefore, it is imperative to study these forces to mitigate their effects. The current study aims to understand the effects of fretting-corrosion as a function of fretting frequencies caused by common physical activities in an in-vitro model of hip modular junctions. The fretting system has a tribological contact condition of flat-on-flat, mounted to a load frame. CoCrMo pins were polished and immersed in a synovial fluid-like electrolyte solution (Bovine calf serum 30 g/l). Electrochemical measurements were made using a potentiostat. Samples then undergo 3600 cycles at 50 µm (to simulate gross slips), with a horizontal load at 200 N, and a frequency of 0.5 Hz, 0.7 Hz, 1 Hz, and 1.5 Hz to simulate Sit Down-Stand Up, Stair Climb, Walking, and Jogging, respectively. Worn surfaces were then examined under optical and scanning electron microscopy. The evolution of free potential as a function of time for tested frequencies shows the initial potential drop and stabilized trend in the potential evolution. The sample group at a higher frequency displays a higher tendency of corrosion than a lower frequency; however, the dissipation energy decreases as a function of fretting frequency. Both electrochemical and mechanical responses correlate to the variation in the fretting frequencies. Organometallic complexes were found on the surfaces of the samples that were subjected to a slower frequency of fretting, whereas mechanical grooving was noticed on samples with a faster frequency. Hence, these preliminary studies suggest that implant failure rates may be altered based on fretting-frequencies induced by physical activity. Further studies will be required to verify the findings and explore the potential role of fretting frequency in the damage modes of the modular junction.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Animais , Bovinos , Corrosão , Teste de Materiais , Desenho de Prótese , Falha de Prótese , Propriedades de Superfície
6.
Clin Orthop Relat Res ; 479(9): 2083-2096, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019490

RESUMO

BACKGROUND: Fretting and corrosion in metal-on-polyethylene total hip arthoplasty (THA) modular junctions can cause adverse tissue reactions that are responsible for 2% to 5% of revision surgeries. Damage within cobalt-chromium-molybdenum (CoCrMo) alloy femoral heads can progress chemically and mechanically, leading to damage modes such as column damage, imprinting, and uniform fretting damage. At present, it is unclear which of these damage modes are most detrimental and how they may be linked to implant alloy metallurgy. The alloy microstructure exhibits microstructural features such as grain boundaries, hard phases, and segregation bands, which may enable different damage modes, higher material loss, and the potential risk of adverse local tissue reactions. QUESTIONS/PURPOSES: In this study, we asked: (1) How prevalent is chemically dominated column damage compared with mechanically dominated damage modes in severely damaged metal-on-polyethylene THA femoral heads made from wrought CoCrMo alloy? (2) Is material loss greater in femoral heads that underwent column damage? (3) Do material loss and the presence of column damage depend on alloy microstructure as characterized by grain size, hard phase content, and/or banding? METHODS: Surgically retrieved wrought CoCrMo modular femoral heads removed between June 2004 and June 2019 were scored using a modified version of the Goldberg visually based scoring system. Of the total 1002 heads retrieved over this period, 19% (190 of 1002) were identified as severely damaged, exhibiting large areas of fretting scars, black debris, pits, and/or etch marks. Of these, 43% (81 of 190) were excluded for metal-on-metal articulations, alternate designs (such as bipolar, dual-mobility, hemiarthroplasty, metal adaptor sleeves), or previous sectioning of the implant for past studies. One sample was excluded retroactively as metallurgical analysis revealed that it was made of cast alloy, yielding a total of 108 for further analysis. Information on patient age (57 ± 11 years) and sex (56% [61 of 108] were males), reason for removal, implant time in situ (99 ± 78 months), implant manufacturer, head size, and the CoCrMo or titanium-based stem alloy pairing were collected. Damage modes and volumetric material loss within the head tapers were identified using an optical coordinate measuring machine. Samples were categorized by damage mode groups by column damage, imprinting, a combination of column damage and imprinting, or uniform fretting. Metallurgical samples were processed to identify microstructural characteristics of grain size, hard phase content, and banding. Nonparametric Mann-Whitney U and Kruskal-Wallis statistical tests were used to examine volumetric material loss compared with damage mode and microstructural features, and linear regression was performed to correlate patient- and manufacturer-specific factors with volumetric material loss. RESULTS: Chemically driven column damage was seen in 48% (52 of 108) of femoral heads, with 34% (37 of 108) exhibiting a combination of column damage and imprinting, 12% (13 of 108) of heads displaying column damage and uniform fretting, and 2% (2 of 108) exhibiting such widespread column damage that potentially underlying mechanical damage modes could not be verified. Implants with column damage showed greater material loss than those with mechanically driven damage alone, with median (range) values of 1.2 mm3 (0.2 to 11.7) versus 0.6 mm3 (0 to 20.7; p = 0.03). Median (range) volume loss across all femoral heads was 0.9 mm3 (0 to 20.7). Time in situ, contact area, patient age, sex, head size, manufacturer, and stem alloy type were not associated with volumetric material loss. Banding of the alloy microstructure, with a median (range) material loss of 1.1 mm3 (0 to 20.7), was associated with five times higher material loss compared with those with a homogeneous microstructure, which had a volume loss of 0.2 mm3 (0 to 4.1; p = 0.02). Hard phase content and grain size showed no correlation with material loss. CONCLUSION: Chemically dominated column damage was a clear indicator of greater volume loss in this study sample of 108 severely damaged heads. Volumetric material loss strongly depended on banding (microstructural segregations) within the alloy. Banding of the wrought CoCrMo microstructure should be avoided during the manufacturing process to reduce volumetric material loss and the release of corrosion products to the periprosthetic tissue. CLINICAL RELEVANCE: Approximately 30% of THAs rely on wrought CoCrMo femoral heads. Most femoral heads in this study exhibited a banded microstructure that was associated with larger material loss and the occurrence of chemically dominated column damage. This study suggests that elimination of banding from the alloy could substantially reduce the release of implant debris in vivo, which could potentially also reduce the risk of adverse local tissue reactions to implant debris.

7.
J Mech Behav Biomed Mater ; 118: 104484, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33773236

RESUMO

Total hip replacements (THR) are becoming an common orthopedic surgucal procedure in the United States (332 K/year in 2017) to relieve pain and improve the mobility of those that are affected by osteoarthritis, ankylosing spondylitis, or injury. However, complications like tribocorrosion, or material degradation due to friction and corrosion, may result in THR failure. Unfortunately, few strategies to non-invasively diagnose early-stage complications are reported in literature, leading to implant complications being detected after irreversible damage. Therefore, the main objective of this study proposes the utilization of acoustic emission (AE) to continuously monitor implant materials, CoCrMo and Ti6Al4V, and identify degradations formed during cycles of sleeping, standing, and walking by correlating them to potential and friction coefficient behavior. AE activity detected from the study correlates with the friction coefficient and open-circuit potential observed during recreated in-vitro standing, walking, and sleeping cycles. It was found that the absolute energy level obtained from AE increased as the friction coefficient increased, potential decreased, and wear volume loss increased. Through the results, higher friction coefficient and AE activity were observed in Ti6Al4V alloys while there was also a significant drop in potential, indicating increased tribocorrosion activity. Therefore, AE can be utilized to predict material degradations as a non-invasive method based on the severity of abnormality of the absolute energy and hits emitted. The correlation between potential, friction coefficient, and AE activity was further confirmed through profilometry which showed more material degradation in Ti6Al4V than CoCrMo. Through these evaluations, it was demonstrated that AE could be utilized to identify the deformations and failure modes of implant materials caused by tribocorrosion.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Acústica , Ligas , Corrosão , Fricção , Titânio
8.
J Mech Behav Biomed Mater ; 118: 104443, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33752094

RESUMO

Contemporary hip implants feature a modular design. Increased reported failure rates associated with the utilization of modular junctions have raised many clinical concerns. Typically, these modular interfaces contain circumferential machining marks (threads or microgrooves), but the effect of the machining marks on the fretting-corrosion behavior of total hip implant materials is unknown. This study reports the effects of microgrooves on the fretting-corrosion behavior of hip implant materials. The flat portions of two cylindrical, polished, CrCrMo alloy pins were loaded horizontally against one rectangular Ti alloy rod. Two surface preparation groups were used for the Ti6Al4V rod (polished and machined). The polished group was prepared using the same methods as the CoCrMo pins. The machined samples were prepared by creating parallel lines on the rod surfaces to represent microgrooves present on the stem tapers of head-neck modular junctions. Newborn calf serum (30 g/L protein content; 37 °C) at pH of levels of 7.6 and 3.0 were used to simulate the normal joint fluid and a lowered pH within a crevice, respectively. The samples were tested in a fretting corrosion apparatus under a 200N normal force and a 1Hz sinusoidal fretting motion with a displacement amplitude of 25 µm. All electrochemical measurements were performed with a potentiostat in a three-electrode configuration. The results show significant differences between machined samples and polished samples in both electrochemical and mechanical responses. In all cases, the magnitude of the drop in potential was greater in the machined group compared to the polished group. The machined group showed a lower total dissipated friction energy for the entire test compared to the polished group. Additionally, the potentiostatic test measurements revealed a higher evolved charge in the machined group compared to the polished group at both pH conditions (pH 7.6 and 3.0). The machined surfaces lowered the overall dissipated friction energy at pH 7.6 compared to pH 3.0, but also compromised electrochemical performance in the tested conditions. Therefore, the role of synergistic interaction of wear and corrosion with surface topographical changes is evident from the outcome of the study. Despite the shift towards higher electrochemical destabilization in the machined group, both polished and machined groups still exhibited a mechanically dominated degradation.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Corrosão , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Teste de Materiais , Desenho de Prótese , Falha de Prótese , Propriedades de Superfície
9.
Cell Biol Toxicol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33415469

RESUMO

The complexity of cobalt-chromium-molybdenum (CoCrMo) nanoparticles generated from the hip modular taper interfaces resulted in inconclusive outcomes on the level of toxicity in orthopedic patients. We used a hip simulator to generate physiologically relevant CoCrMo degradation products (DPs) to demonstrate the variation in the level of toxicity in neurons in comparison to processed degradation products (PDPs). The study outcomes indicate that DP induces a higher level of DNA damage in the form of double- and single-stranded DNA breaks and alkaline labile DNA adducts versus PDPs. The scientific advancements of this study are the following: (i) how DPs mimic more closely to the implant debris from hip implants in terms of bioactivity, (ii) how hip implant debris causes local and systemic issues, and (iii) methods to augment the biologic impact of implant debris. We discovered that DP is bioactive compared with PDP, and this should be considered in the toxicity evaluation related to implants. • The physicochemical characteristics of the CoCrMo is a major factor to consider for implant-related cytotoxicity or genotoxicity experimental design. • Elevated levels of intracellular ROS induced by the physiologically relevant wear particle are detrimental to the neuronal cells. • The DP can induce variation in DNA replication dynamics compared to PDP.

10.
Med Biol Eng Comput ; 58(8): 1637-1650, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32533510

RESUMO

Nowadays, acoustic emission (AE) has its applications in various areas, including mechanical, civil, underwater acoustics, and biomedical engineering. It is a non-destructive evaluation (NDE) and a non-intrusive method to detect active damage mechanisms such as crack growth, delamination, and processes such as friction, continuous wear, etc. The application of AE in orthopedics, especially in hip implant monitoring, is an emerging research field. This article presents a thorough literature review associated with the implementation of acoustic emission as a diagnostic tool for total hip replacement (THR) implants. Structural health monitoring of an implant via acoustic emission and vibration analysis is an evolving research area in the field of biomedical engineering. A review of the literature reveals a lack of reliable, non-invasive, and non-traumatic early warning methods to evaluate implant loosening that can help to identify patients at risk for osteolysis prior to implant failure. Developing an intelligent acoustic emission technique with excellent condition monitoring capabilities will be an achievement of great importance that fills the gaps or drawbacks associated with osteolysis/implant failure. Graphical abstract.


Assuntos
Artroplastia de Quadril/métodos , Monitorização Fisiológica/métodos , Procedimentos Ortopédicos/métodos , Acústica , Animais , Fenômenos Biomecânicos/fisiologia , Fricção/fisiologia , Prótese de Quadril , Humanos , Teste de Materiais/métodos , Falha de Prótese , Vibração
11.
Nanomaterials (Basel) ; 10(3)2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32235802

RESUMO

Diabetic retinopathy (DR), Retinopathy of Pre-maturity (ROP), and Age-related Macular Degeneration (AMD) are multifactorial manifestations associated with abnormal growth of blood vessels in the retina. These three diseases account for 5% of the total blindness and vision impairment in the US alone. The current treatment options involve heavily invasive techniques such as frequent intravitreal administration of anti-VEGF (vascular endothelial growth factor) antibodies, which pose serious risks of endophthalmitis, retinal detachment and a multitude of adverse effects stemming from the diverse physiological processes that involve VEGF. To overcome these limitations, this current study utilizes a micellar delivery vehicle (MC) decorated with an anti-angiogenic peptide (aANGP) that inhibits αvß3 mediated neovascularization using primary endothelial cells (HUVEC). Stable incorporation of the peptide into the micelles (aANGP-MCs) for high valency surface display was achieved with a lipidated peptide construct. After 24 h of treatment, aANGP-MCs showed significantly higher inhibition of proliferation and migration compared to free from aANGP peptide. A tube formation assay clearly demonstrated a dose-dependent angiogenic inhibitory effect of aANGP-MCs with a maximum inhibition at 4 µg/mL, a 1000-fold lower concentration than that required for free from aANGP to display a biological effect. These results demonstrate valency-dependent enhancement in the therapeutic efficacy of a bioactive peptide following conjugation to nanoparticle surfaces and present a possible treatment alternative to anti-VEGF antibody therapy with decreased side effects and more versatile options for controlled delivery.

12.
J Orthop Res ; 38(2): 393-404, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31436344

RESUMO

Corrosion at modular junctions of total hip replacement (THR) remains a major concern today. Multiple types of damage modes have been identified at modular junctions, correlated with different corrosion characteristics that may eventually lead to implant failure. Recently, within the head-taper region of the CoCrMo retrieval implants, cell-like features and trails of etching patterns were observed that could potentially be linked to the involvement of cells of the periprosthetic region. However, there is no experimental evidence to corroborate this phenomenon. Therefore, we aimed to study the potential role of periprosthetic cell types on corrosion of CoCrMo alloy under different culture conditions, including the presence of CoCrMo wear debris. Cells were incubated with and without CoCrMo wear debris (obtained from a hip simulator) with an average particle size of 119 ± 138 nm. Electrochemical impedance spectroscopy (EIS) was used to evaluate the corrosion tendency, corrosion rate, and corrosion kinetics using the media after 24 h of cell culture as the electrolyte. Results of the study showed that there was lower corrosion resistance (p < 0.02) and higher capacitance (p < 0.05) within cell media from macrophages challenged with particles when compared with the other media conditions studied. The potentiodynamic results were also in agreement with the EIS values, showing significantly higher corrosion tendency (low Ecorr ) (p < 0.0001) and high Icorr (p < 0.05) in media from challenged macrophages compared with media with H2 O2 solution. Overall, the study provides in vitro experimental evidence for the possible role of macrophages in altering the chemical environment within the crevice and thereby accelerating corrosion of CoCrMo alloy. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:393-404, 2020.


Assuntos
Prótese de Quadril/efeitos adversos , Macrófagos/fisiologia , Artroplastia de Quadril/efeitos adversos , Linhagem Celular , Corrosão , Técnicas Eletroquímicas , Humanos , Testes de Toxicidade
13.
Acta Biomater ; 101: 586-597, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678260

RESUMO

Evidence that macrophages can play a role in accelerating corrosion in CoCrMo alloy in total hip replacement (THR) interfaces leads to questions regarding the underlying cellular mechanisms and immunological responses. Hence, we evaluated the role of macrophages in corrosion processes using the cell culture supernatant from different conditions and the effect of wear particles on macrophage dynamics. Monocytes were exposed to CoCrMo wear particles and their effect on macrophage differentiation was investigated by comparisons with M1 and M2 macrophage differentiation. Corrosion associated macrophages (MCA macrophages) exhibited upregulation of TNF-α, iNOS, STAT-6, and PPARG and down-regulation of CD86 and ARG, when compared to M1 and M2 macrophages. MCA cells also secreted higher levels of IL-8, IL-1ß, IL-6, IL-10, TNF-α, and IL-12p70 than M1 macrophages and/or M2 macrophages. Our findings revealed variation in macrophage phenotype (MCA) induced by CoCrMo wear particles in generating a chemical environment that induces cell-accelerated corrosion of CoCrMo alloy at THR modular interfaces. STATEMENT OF SIGNIFICANCE: Fretting wear and corrosion within the implant's modular taper junction are prominent causes of implant failure, as they promote the release of corrosion products and subsequent development of adverse local tissue reactions. Being a multifactorial process, several in vitro models have been developed to recreate the in vivo corrosion process, often summarized as mechanically-assisted crevice corrosion. Considering the excellent corrosion properties of CoCrMo alloy, the severity of chemically-generated damage observed at the modular interface has been surprising and poorly understood. The aim of the current study is to provide a better understanding of macrophages and their plasticity at the THR taper interface when they encounter wear debris from CoCrMo alloy. This is a preliminary study along the path towards determining the mechanism(s) of CAC.


Assuntos
Artroplastia de Quadril , Macrófagos/patologia , Falha de Prótese , Ligas/química , Diferenciação Celular , Polaridade Celular , Corrosão , Citocinas/metabolismo , Técnicas Eletroquímicas , Cabeça do Fêmur/patologia , Cabeça do Fêmur/ultraestrutura , Perfilação da Expressão Gênica , Humanos , Cinética , Macrófagos/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células THP-1
14.
Biomed Eng Lett ; 9(2): 169-179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31168422

RESUMO

The goal of this paper is to review the advantages and disadvantages of the various treatment options of temporomandibular joint (TMJ) total joint replacement (TJR). TMJ articles published within the last 20 years were reviewed to collect the information on non-invasive and invasive TMD treatment methods. Recent technological advancements helped the evolution of treatment methods and offered significant value to TMD patients and surgeons. Considering the TMD levels, the therapeutic procedures can involve general health examiniations, physical therapy, medication, oral rehabilation or as an end stage clinical invention, temporomandibular joint replacement. In fact when intra-articular TMD is present, the effective treatment method appears to be TJR. However, concern for infection, material hypersensitivity, device longevity and screws loosening issues still exists. Further combined research utilizing the knowledge and expertise of, surgeons, material scientists, and bioengineers is needed for the development of improved TMD therapeutic treatment.

15.
J Mech Behav Biomed Mater ; 96: 152-164, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31035066

RESUMO

The long-term survivability of the implants is strongly influenced by the osseointegration aspects of the metal-bone interface. In this study, biological materials such as fibrinogen and fibrin are used to functionalize titanium surfaces to enhance the ability of implants to interact with human tissues for accelerated osseointegration. The biofunctionalized samples that were assessed by White Light Microscope, Scanning Electron Microscope and Water Contact Angle for surface properties proved samples etched with HF/HNO3 to be better than HCl/H2SO4 in terms of having optimum roughness and hydrophilicity for our further experiments. To further investigate the in vitro osseointegration of the biofunctionalized samples, Osteoblasts were cultured on the surfaces to assess cell proliferation, adhesion, gene expression as well as the mineralization process. Further bacterial adhesion (Enterococcus faecalis) and electrochemical evaluation of surface coating stability were carried out. Results of the study show that the biofunctionalized surfaces provided high cell proliferation, adherence, gene expression, and mineralization compared to other control surfaces hence proving them to have efficient and enhanced osseointegration. Also, bacterial adhesion studies show that there is no augmented growth of bacteria on the biofunctionalized samples in comparison to control surfaces. Electrochemical studies proved the existence of a stable protein layer on the bio functionalized surfaces. Such a method can reduce the time for osseointegration that can decrease risks in early failures of implants due to its enhanced hydrophilicity and cytocompatibility.


Assuntos
Fenômenos Químicos , Fibrina/química , Fibrinogênio/química , Titânio/química , Titânio/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Implantes Dentários , Eletroquímica , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Osseointegração/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Estabilidade Proteica , Propriedades de Superfície
16.
Oncogene ; 38(28): 5643-5657, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30967636

RESUMO

Platinum-based drugs such as cisplatin (CP) are the first-line chemotherapy for non-small-cell lung carcinoma (NSCLC). Unfortunately, NSCLC has a low response rate to CP and acquired resistance always occurs. Histone methylation regulates chromatin structure and is implicated in DNA repair. We hypothesize histone methylation regulators are involved in CP resistance. We therefore screened gene expression of known histone methyltransferases and demethylases in three NSCLC cell lines with or without acquired resistance to CP. JMJD2s are a family of histone demethylases that remove tri-methyl groups from H3K9 and H3K36. We found expression of several JMJD2 family genes upregulated in CP-resistant cells, with JMJD2B expression being upregulated in all three CP-resistant NSCLC cell lines. Further analysis showed increased JMJD2 protein expression coincided with decreased H3K9me3 and H3K36me3. Chemical inhibitors of JMJD2-family proteins increased H3K9me3 and H3K36me3 levels and sensitized resistant cells to CP. Mechanistic studies showed that JMJD2 inhibition decreased chromatin association of ATR and Chk1 and inhibited the ATR-Chk1 replication checkpoint. Our results reveal that JMJD2 demethylases are potential therapeutic targets to overcome CP resistance in NSCLC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Quinase 1 do Ponto de Checagem/metabolismo , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji , Neoplasias Pulmonares/metabolismo , Metilação
17.
Dent Mater ; 35(6): 900-908, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30975484

RESUMO

OBJECTIVES: Surface conditioning of enamel and dentin is a key step during adhesive restorative procedures and strategies. The aim of this study was to investigate the effectiveness of five α-hydroxy-acids (AHAs) as enamel and dentin surface etchants. METHODS: Enamel and dentin specimens were prepared from human molars to determine the depth of demineralization by optical profilometry (Δz), the resin bond strength to enamel and dentin (µTBS), the micro-permeability of dentin-resin interfaces, and the gelatinolytic activity of dentin matrix induced by AHAs [glycolic (GA), lactic (LA), citric (CA), malic (MI) and tartaric (TA)] and controls [phosphoric (PA) and maleic (MA)]. All acids were prepared at 35% concentration. Adhesion studies employed Adper Single Bond Plus bonding system. Data were individually processed and analyzed by ANOVA, post-hoc tests and Pearson correlations (α = 0.05). RESULTS: AHA exhibited statistically lower depth of demineralization of enamel and dentin (average 4 fold) than controls (p < 0.001). In enamel, MA and PA etching resulted in higher µTBS than AHA groups (p < 0.001). In dentin, GA, TA, CI and LA etching resulted in statistically similar µTBS than PA (p < 0.05). The hybrid-layer (HL) thickness and interfacial micro-permeability intensity were statistically lower for AHA groups (p < 0.05). A significant positive correlation was observed between the intensity of micro-permeability and the thickness of HL (p < 0.05). AHA etchants elicited lower dentin enzymatic activity than controls (p < 0.05). SIGNIFICANCE: AHAs effectively etched enamel and dentin surfaces. In particular, GA and TA resulted in suitable µTBS and sealing ability as well as induced less gelatinolytic activity in dentin than PA and MA.


Assuntos
Colagem Dentária , Esmalte Dentário , Dentina , Adesivos Dentinários , Humanos , Hidroxiácidos , Teste de Materiais , Ácidos Fosfóricos , Cimentos de Resina , Resistência à Tração
18.
J Prosthodont ; 28(2): e510-e518, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29508487

RESUMO

PURPOSE: In the field of prosthodontics, patients often require complex and extensive restorative care. This can involve the use of dental restorations to restore teeth on both the maxillary and mandibular arch. Current literature has evaluated the wear properties of different dental ceramics against enamel, but studies regarding dental ceramics opposing one another are limited. The purpose of this study was to assess the wear potential and wear behavior of CAD/CAM zirconia (ZR) and lithium disilicate (LD) materials against a similar ceramic material, and how the surface finish of these dental ceramics might affect patterns of wear. MATERIALS AND METHODS: Using a sphere-on-plate tribometer system, different surface finishes (glazed-G and glazed then polished-GP) of ZR and LD were evaluated following wear simulation. Artificial saliva of physiologic pH was used as a lubricant during wear simulation at 37°C. The coefficient of friction (COF) was calculated during the wear simulation. After wear simulation was complete, volume loss, surface roughness, and surface characterization of the specimens were analyzed using white-light interferometry and scanning electron microscopy (SEM). Statistical significance between materials and surface finish was established with two-way ANOVA and Bonferroni post hoc test (α = 0.05). RESULTS: Based on the 2-way ANOVA, material (p = 0.002) significantly affected the COF. LD showed a higher COF (p = 0.002) than ZR. Material (p < 0.001) and surface finish (p = 0.004) significantly affected the surface roughness inside the scar. ZR had significantly lower surface roughness compared to LD (p < 0.001). For outside scar, surface finish (p < 0.001) significantly affected the surface roughness. Polished specimens showed significantly higher roughness compared to glazed specimens for both inside (p = 0.004) and outside scar (p < 0.001). For volume loss, material (p < 0.001) and the interaction between material and surface finish (p < 0.001) were statistically significant. LD had higher volume loss than ZR (p < 0.001). For both glazed and polished finished, LD-G and LD-GP had significantly higher volume loss than ZR-G (p = 0.028), and ZR-GP (p < 0.001), respectively. SEM analysis indicated particle build-up and a grooving mechanism of wear for the LD-GP specimens. This suggested a three-body wear phenomenon occurring for LD-GP specimens, which was not visible in SEM imaging for other specimen types. CONCLUSIONS: This study demonstrated the resistance to wear and low abrasiveness of ZR when compared to LD in a simulated masticatory environment. This can be best explained by the increased strength of ZR, and the introduction of three-body wear to LD specimens from the accumulation of embedded wear debris onto its surface. Wear data and comparison of SEM images following wear simulation confirmed this interpretation.


Assuntos
Cerâmica/química , Desenho Assistido por Computador , Falha de Restauração Dentária , Porcelana Dentária , Teste de Materiais , Microscopia Eletrônica de Varredura , Saliva Artificial/química , Propriedades de Superfície , Zircônio
19.
ACS Biomater Sci Eng ; 5(9): 4817-4824, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-33448824

RESUMO

Developing coatings for various applications is an area of research of uttermost importance, to protect surfaces from severe damage by improving the wear and corrosion resistance of the materials. Recently, there has been increasing interest in ceramic coatings for biomedical applications, as the surface may become more inert in nature for the biological reactions and potentially increase the lifespan of the implants and minimize the side effects on the patients. Hence this study is focused on the tribocorrosion behavior of the ceramic coatings for the hip implant application on commonly used implant titanium alloy. The three types of the ceramic coatings are conventional monolithic micron alumina (IDA), micron alumina-40 wt % yttria-stabilized zirconia (YSZ) composite coating (IDAZ), and by-layer nanostructured alumina-13 wt % titania/YSZ (IDZAT) on Ti-6Al-4V alloy. A series of tests, under free potential and potentiostatic mode, were conducted using a hip simulator tribocorrosion setup under simulated joint fluid (bovine calf serum with protein concentration 30g/L). The tribological conditions are pin-on-ball contact with a load of 16N (approximately contact pressure of 50 MPa), the frequency of 1 Hz (walking frequency), and with an amplitude of 30°. The tribocorrosion studies clearly revealed that the coatings have better wear and corrosion resistance and the predominant damage mechanism was mechanical wear rather than corrosion. Among the coatings, the IDZAT shows enhanced tribocorrosion performance by exhibiting more positive OCP, no induced current, and a lower coefficient of friction.

20.
J Oral Maxillofac Surg ; 76(10): 2074-2080, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29772190

RESUMO

PURPOSE: The aim of this pilot study was to assay metal concentrations in the serum of patients who had undergone dental implant placement, orthognathic surgery using rigid metal fixation plates and screws, and total temporomandibular joint replacement (TMJ TJR). MATERIALS AND METHODS: Thirty patients were identified and included in this pilot study. Sixteen patients (9 men and 8 women), with an average age of 44 years (range, 19 to 79 yr), provided informed consent to participate and were divided into 3 study groups with 4 patients in each (group 1, orthognathic surgery; group 2, TMJ TJR; and group 3, dental implant placement). A control group consisted of volunteers without any implanted metallic devices. Blood samples for serum metal analysis were obtained and analyzed in accordance with the standardized collection and testing protocols used at the Trace Metal Analysis Laboratory of the Department of Orthopedic Surgery at the Rush University Medical Center (Chicago, IL). RESULTS: All control participants had levels below the normal reference range for all serum markers assessed. In the orthognathic group, 1 patient had an increased serum cobalt level. In the TMJ TJR group, 1 patient had an increased serum cobalt level and another patient had an increased serum chromium level. In the dental implant group, 1 patient had an increased serum titanium level and another had increased serum levels of titanium and chromium. CONCLUSIONS: This is the first study to report on the release of metal into the bloodstream in patients with different maxillofacial implanted metallic objects. The results raise questions regarding the types and magnitude of metal released from maxillofacial reconstruction devices and their potential long-term local and systemic effects. Future large-scale prospective studies involving serial measurements in homogeneous groups of patients could further elucidate the impact of these findings.


Assuntos
Artroplastia de Substituição/métodos , Cromo/sangue , Cobalto/sangue , Implantes Dentários , Cirurgia Ortognática/métodos , Articulação Temporomandibular/cirurgia , Titânio/sangue , Adulto , Idoso , Feminino , Humanos , Prótese Articular , Masculino , Pessoa de Meia-Idade , Projetos Piloto
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