Fretting and Fretting Corrosion Behavior of Additively Manufactured Ti-6Al-4V and Ti-Nb-Zr Alloys in Air and Physiological Solutions.

Additive manufacturing (AM) of orthopedic implants has increased in recent years, providing benefits to surgeons, patients, and implant companies. Both traditional and new titanium alloys are under consideration for AM-manufactured implants. However, concerns remain about their wear and corrosion (tribocorrosion) performance. In this study, the effects of fretting corrosion were investigated on AM Ti-29Nb-21Zr (pre-alloyed and admixed) and AM Ti-6Al-4V with 1% nano yttria-stabilized zirconia (nYSZ). Low cycle (100 cycles, 3 Hz, 100 mN) fretting and fretting corrosion (potentiostatic, 0 V vs. Ag/AgCl) methods were used to compare these AM alloys to traditionally manufactured AM Ti-6Al-4V. Alloy and admixture surfaces were subjected to (1) fretting in the air (i.e., small-scale reciprocal sliding) and (2) fretting corrosion in phosphate-buffered saline (PBS) using a single diamond asperity (17 µm radius). Wear track depth measurements, fretting currents and scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS) analysis of oxide debris revealed that pre-alloyed AM Ti-29Nb-21Zr generally had greater wear depths after 100 cycles (4.67 +/- 0.55 µm dry and 5.78 +/- 0.83 µm in solution) and higher fretting currents (0.58 +/- 0.07 µA). A correlation (R2 = 0.67) was found between wear depth and the average fretting currents with different alloys located in different regions of the relationship. No statistically significant differences were observed in wear depth between in-air and in-PBS tests. However, significantly higher amounts of oxygen (measured by oxygen weight % by EDS analysis of the debris) were embedded within the wear track for tests performed in PBS compared to air for all samples except the ad-mixed Ti-29Nb-21Zr (p = 0.21). For traditional and AM Ti-6Al-4V, the wear track depths (dry fretting: 2.90 +/- 0.32 µm vs. 2.51 +/- 0.51 µm, respectively; fretting corrosion: 2.09 +/- 0.59 µm vs. 1.16 +/- 0.79 µm, respectively) and fretting current measurements (0.37 +/- 0.05 µA vs. 0.34 +/- 0.05 µA, respectively) showed no significant differences. The dominant wear deformation process was plastic deformation followed by cyclic extrusion of plate-like wear debris at the end of the stroke, resulting in ribbon-like extruded material for all alloys. While previous work documented improved corrosion resistance of Ti-29Nb-21Zr in simulated inflammatory solutions over Ti-6Al-4V, this work does not show similar improvements in the relative fretting corrosion resistance of these alloys compared to Ti-6Al-4V.

Understanding the impacts of chronic pain on autistic adolescents and effective pain management: a reflexive thematic analysis adolescent-maternal dyadic study.

OBJECTIVE: Sensory elements are core features in chronic pain and autism, yet knowledge of the pain experience in autistic adolescents is limited. Little is known regarding how autistic adolescents experience chronic pain, manage their pain and perceive psychological treatment for their chronic pain. METHODS: Ten autistic adolescents (6 female, 3 male, and 1 self-identified as agender) with chronic pain and their mothers (n = 10) participated in semistructured interviews concerning their perceptions of living with chronic pain. Participants were recruited from U.K. pain management services. According to preference, interviews were conducted individually (n = 10) or dyadically (n = 10 participants across 5 dyads). Data were analyzed using inductive reflexive thematic analysis. RESULTS: Two themes were generated. Theme 1, "overstimulated and striving for control" described how adolescents' experience of heightened sensitivity enhanced adolescents' levels of anxiety and subsequent pain, illustrating a reciprocal relationship between anxiety, pain, and sensory elements. Theme 2, "not everyone fits the mold" captured how autistic adolescents positioned themselves as distinct from others due to the unique nature of being autistic and living with pain. This sense of difference negatively impacted adolescents' ability to engage with and benefit from the standard treatment for chronic pain. CONCLUSIONS: Findings suggest that autistic adolescents living with pain experience pain and face barriers to effective pain treatment. Our results identify the need for educational resources to facilitate clinicians to better understand the experience of autistic adolescents living with pain. In turn, such understanding may improve treatment and outcomes in this population.

Increasing temperature accelerates Ti-6Al-4V oxide degradation and selective dissolution: An Arrhenius-based analysis.

Ti-6Al-4V selective dissolution occurs in vivo on orthopedic implants as the leading edge of a pitting corrosion attack. A gap persists in our fundamental understanding of selective dissolution and pre-clinical tests fail to reproduce this damage. While CoCrMo clinical use decreases, Ti-6Al-4V and the crevice geometries where corrosion can occur remain ubiquitous in implant design. Additionally, most additively manufactured devices cleared by the FDA use Ti-6Al-4V. Accelerated preclinical testing, therefore, would aid in the evaluation of new titanium devices and biomaterials. In this study, using temperature, we (1) developed an accelerated pre-clinical methodology to rapidly induce dissolution and (2) investigated the structure-property relationship between the dissolving surface and the oxide layer. We hypothesized that solution temperature and H2O2 concentration would accelerate oxide degradation, increase corrosion kinetics and decrease experimental times. To assess this effect, we selected temperatures above (45 °C), below (24 °C), and at (37 °C) physiological levels. Then, we acquired electrochemical impedance spectra during active ß dissolution, showing significant decreases in oxide polarization resistance (Rp) both over time (p = 0.000) and as temperature increased (p = 0.000). Next, using the impedance response as a guide, we quantified the extent of selective dissolution in scanning electron micrographs. As the temperature increased, the corrosion rate increased in an Arrhenius-dependent manner. Last, we identified three surface classes as the oxide properties changed: undissolved, transition and dissolved. These results indicate a concentration and temperature dependent structure-property relationship between the solution, the protective oxide film, and the substrate alloy. Additionally, we show how supraphysiological temperatures induce structurally similar dissolution to tests run at 37 °C in less experimental time. STATEMENT OF SIGNIFICANCE: Within modular taper junctions of total hip replacement systems, retrieval studies document severe corrosion including Ti-6AL-4V selective dissolution. Current pre-clinical tests and ASTM standards fail to reproduce this damage, preventing accurate screening of titanium-based biomaterials and implant designs. In this study, we induce selective dissolution using accelerated temperatures. Building off previous work, we use electrochemical impedance spectroscopy to rapidly monitor the oxide film during dissolution. We elucidate components of the dissolution mechanism, where oxide degradation precedes pit nucleation within the ß phase. Using an Arrhenius approach, we relate these accelerated testing conditions to more physiologically relevant solution concentrations. In total, this study shows the importance of including adverse electrochemical events like cathodic activation and inflammatory species in pre-clinical testing.

Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high-dose GLP-1 receptor agonists and GLP-1 receptor-based co-agonists.

Type 2 diabetes (T2D), obesity, and nonalcoholic fatty liver disease/nonalacoholic steatohepatitis (NAFLD/NASH) share mutual causalities. Medications that may offer clinical benefits to all three conditions are being developed. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP-1RAs and developing novel GLP-1RA-based co-agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD/NASH complications in clinically meaningful ways. High-dose GLP-1RAs and multi-hormonal strategies including GLP-1R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high-dose GLP-1RAs, unimolecular, and multimolecular GLP-1R-based co-agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP-1R-based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide-spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.

Oxide degradation precedes additively manufactured Ti-6Al-4V selective dissolution: An unsupervised machine learning correlation of impedance and dissolution compared to Ti-29Nb-21Zr.

Additively manufactured (AM) Ti-6Al-4V devices are implanted with increasing frequency. While registry data report short-term success, a gap persists in our understanding of long-term AM Ti-6Al-4V corrosion behavior. Retrieval studies document ß phase selective dissolution on conventionally manufactured Ti-6Al-4V devices. Researchers reproduce this damage in vitro by combining negative potentials (cathodic activation) and inflammatory simulating solutions (H2 O2 -phosphate buffered saline). In this study, we investigate the effects of these adverse electrochemical conditions on AM Ti-6Al-4V impedance and selective dissolution. We hypothesize that cathodic activation and H2 O2 solution will degrade the oxide, promoting corrosion. First, we characterized AM Ti-6Al-4V samples before and after a 48 h -0.4 V hold in 0.1 M H2 O2 /phosphate buffered saline. Next, we acquired nearfield electrochemical impedance spectroscopy (EIS) data. Finally, we captured micrographs and EIS during dissolution. Throughout, we used AM Ti-29Nb-21Zr as a comparison. After 48 h, AM Ti-6Al-4V selectively dissolved. Ti-29Nb-21Zr visually corroded less. Structural changes at the AM Ti-6Al-4V oxide interface manifested as property changes to the impedance. After dissolution, the log-adjusted constant phase element (CPE) parameter, Q, significantly increased from -4.75 to -3.84 (Scm-2 (s)α ) (p = .000). The CPE exponent, α, significantly decreased from .90 to .84 (p = .000). Next, we documented a systematic decrease in oxide polarization resistance before pit nucleation and growth. Last, using k-means clustering, we established a structure-property relationship between impedance and the surface's dissolution state. These results suggest that AM Ti-6Al-4V may be susceptible to in vivo crevice corrosion within modular taper junctions.

Genome-Wide Association Study and Genomic Prediction of Fusarium Wilt Resistance in Common Bean Core Collection.

The common bean (Phaseolus vulgaris L.) is a globally cultivated leguminous crop. Fusarium wilt (FW), caused by Fusarium oxysporum f. sp. phaseoli (Fop), is a significant disease leading to substantial yield loss in common beans. Disease-resistant cultivars are recommended to counteract this. The objective of this investigation was to identify single nucleotide polymorphism (SNP) markers associated with FW resistance and to pinpoint potential resistant common bean accessions within a core collection, utilizing a panel of 157 accessions through the Genome-wide association study (GWAS) approach with TASSEL 5 and GAPIT 3. Phenotypes for Fop race 1 and race 4 were matched with genotypic data from 4740 SNPs of BARCBean6K_3 Infinium Bea Chips. After ranking the 157-accession panel and revealing 21 Fusarium wilt-resistant accessions, the GWAS pinpointed 16 SNPs on chromosomes Pv04, Pv05, Pv07, Pv8, and Pv09 linked to Fop race 1 resistance, 23 SNPs on chromosomes Pv03, Pv04, Pv05, Pv07, Pv09, Pv10, and Pv11 associated with Fop race 4 resistance, and 7 SNPs on chromosomes Pv04 and Pv09 correlated with both Fop race 1 and race 4 resistances. Furthermore, within a 30 kb flanking region of these associated SNPs, a total of 17 candidate genes were identified. Some of these genes were annotated as classical disease resistance protein/enzymes, including NB-ARC domain proteins, Leucine-rich repeat protein kinase family proteins, zinc finger family proteins, P-loopcontaining nucleoside triphosphate hydrolase superfamily, etc. Genomic prediction (GP) accuracy for Fop race resistances ranged from 0.26 to 0.55. This study advanced common bean genetic enhancement through marker-assisted selection (MAS) and genomic selection (GS) strategies, paving the way for improved Fop resistance.

Additively manufactured Ti-29Nb-21Zr shows improved oxide polarization resistance versus Ti-6Al-4V in inflammatory simulating solution.

Retrieval studies in the past two decades show severe corrosion of titanium and its alloys in orthopedic implants. This damage is promoted by mechanically assisted crevice corrosion (MACC), particularly within modular titanium-titanium junctions. During MACC, titanium interfaces may be subject to negative potentials and reactive oxygen species (ROS), generated from cathodic activation and/or inflammation. Additive manufacturing (AM) may be able to produce new, corrosion-resistant titanium alloys and admixtures that are less susceptible to these adverse electrochemical events. In this study, we characterize the impedance and corrosion properties of three new AM titanium materials, including Ti-6Al-4V with added 1% nano-yttria stabilized ZrO2 , admixed Ti-29Nb-21Zr, and pre-alloyed Ti-29Nb-21Zr. We aim to elucidate how these materials perform when subjected to high ROS solutions. We include conventionally and additively manufactured Ti-6Al-4V in our study as comparison groups. A 0.1 M H2 O2 phosphate-buffered saline (PBS) solution, simulating inflammatory conditions, significantly increased biomaterial OCP (-0.14 V vs. Ag/AgCl) compared to PBS only (-0.38 V, p = .000). During anodic polarization, Ti-6Al-4V passive current density more than doubled from 1.28 × 10-7 to 3.81 × 10-7 A/cm2 when exposed to 0.1 M H2 O2 . In contrast, Ti-29Nb-21Zr passive current density remained relatively unchanged, slightly increasing from 7.49 × 10-8 in PBS to 9.31 × 10-8 in 0.1 M H2 O2 . Ti-29Nb-21Zr oxide polarization resistance (Rp ) was not affected by 0.1 M H2 O2 , maintaining a high value (1.09 × 106 vs. 1.89 × 106 Ω cm2 ), while Ti-6Al-4V in 0.1 M H2 O2 solution had significantly diminished Rp (4.38 × 106 in PBS vs. 7.24 × 104 Ω cm2 in H2 O2 ). These results indicate that Ti-29Nb-21Zr has improved corrosion resistance in ROS containing solutions when compared with Ti-6Al-4V based biomaterials.

Cytochrome P450-soluble epoxide hydrolase derived linoleic acid oxylipins and cognitive performance in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) increases the risk of cognitive decline and dementia. Disruptions in the cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) pathway have been reported in T2DM, obesity and cognitive impairment. We examine linoleic acid (LA)-derived CYP450-sEH oxylipins and cognition in T2DM and explore potential differences between obese and nonobese individuals. The study included 51 obese and 57 nonobese participants (mean age 63.0 ± 9.9, 49% women) with T2DM. Executive function was assessed using the Stroop Color-Word Interference Test, FAS-Verbal Fluency Test, Digit Symbol Substitution Test, and Trails Making Test-Part B. Verbal memory was assessed using the California Verbal Learning Test, second Edition. Four LA-derived oxylipins were analyzed by ultra-high-pressure-LC/MS, and the 12,13-dihydroxyoctadecamonoenoic acid (12,13-DiHOME) considered the main species of interest. Models controlled for age, sex, BMI, glycosylated hemoglobin A1c, diabetes duration, depression, hypertension, and education. The sEH-derived 12,13-DiHOME was associated with poorer executive function scores (F1,98 = 7.513, P = 0.007). The CYP450-derived 12(13)-epoxyoctadecamonoenoic acid (12(13)-EpOME) was associated with poorer executive function and verbal memory scores (F1,98 = 7.222, P = 0.008 and F1,98 = 4.621, P = 0.034, respectively). There were interactions between obesity and the 12,13-DiHOME/12(13)-EpOME ratio (F1,97 = 5.498, P = 0.021) and between obesity and 9(10)-epoxyoctadecamonoenoic acid (9(10)-EpOME) concentrations (F1,97 = 4.126, P = 0.045), predicting executive function such that relationships were stronger in obese individuals. These findings suggest that the CYP450-sEH pathway as a potential therapeutic target for cognitive decline in T2DM. For some markers, relationships may be obesity dependent.

Low cycle fretting and fretting corrosion properties of low carbon CoCrMo and additively manufactured CoCrMoW alloys for dental and orthopedic applications.

Additive manufacturing (AM) of CoCrMo metallic implants is growing in the orthopedic and dental fields. This is due to the traditional alloy's excellent corrosion resistance and mechanical properties. AM processes like selective laser melting (SLM) require less time, materials, and waste than casting or subtractive manufacturing complex-geometry structures (bridges, partial dentures, etc.). The objective of this work was to investigate the low cycle tribological and tribocorrosion characteristics of AM CoCrMoW alloys compared to wrought LC CoCrMo (ASTM F-1537) to assess this AM alloy's performance. Fretting and tribocorrosion testing was performed in air (wear only), PBS (wear + corrosion), and PBS with 10 mM H2 O2 (wear + corrosion + inflammation) by a single diamond asperity. No variation between alloys in volume of material removed (p = .12), volume of plastic deformation (p = .13), and scratch depth (p = .84) showed that AM was substantially similar in wear resistance to LC in air and PBS. AM exhibited significantly higher fretting currents (p < .01) at loads up to 100 mN ( I AM PBS = 57 nA and I AM H 2 O 2 = 49 nA) than LC CoCrMo ( I LC PBS = 30 nA) and ( I LC H 2 O 2 = 29 nA). In PBS, wear track depth linearly correlates to fretting current, averaged over 100 cycles. Additionally, fretting currents of both alloys were significantly lower in simulated inflammatory conditions compared to PBS alone. AM alloy has generally similar wear and tribocorrosion resistance to wrought LC CoCrMo and would be ideal for patient specific dentistry or orthopedics where precise, complex geometries are required.

The Year 2022 in biomaterials research: A perspective from the editors of six leading journals.

The field of biomaterials science is highly active, with a steadily increasing number of publications and new journals being founded. This article brings together contributions from the editors of six leading journals in the area of biomaterials science and engineering. Each contributor highlights specific advances, topics, and trends that have emerged through the publications in their respective journal in the calendar year 2022. It presents a global perspective on a wide range of material types, functionalities, and applications. The highlighted topics include a diversity of biomaterials; from proteins, polysaccharides, and lipids to ceramics, metals, advanced composites, and a variety of new forms of these materials. Important advances in dynamically functional materials are presented, including a range of fabrication techniques such as bioassembly, 3D bioprinting and microgel formation. Similarly, several applications are highlighted in drug and gene delivery, biological sensing, cell guidance, immunoengineering, electroconductivity, wound healing, infection resistance, tissue engineering, and treatment of cancer. The goal of this paper is to provide the reader with both a broad view of recent biomaterials research, as well as expert commentary on some of the key advances that will shape the future of biomaterials science and engineering.

Retrieval analysis of the Essure® micro insert female sterilization implant: Methods for metal ion and microscopic analysis.

The Essure® Device is a female sterilization implant comprised of four alloys (Ni-Ti, 316L SS, Pt-Ir and Sn-Ag) and Dacron fibers. As part of the mandated 522 post-market surveillance study, implant retrieval and metal-ion analysis methods were developed separate from patient clinical data, to quantify trace metal ions found in tissue and to assess implant degradation present. Three segments of tissue (proximal implant, distal implant, and tissue distal from the implant) stored in neutral buffered formalin, were retrieved. Tissue was prepared for metal ion analysis using inductively coupled mass spectrometry (ICP-MS). Implant sections from four patients, were analyzed using digital optical microscopy (DOM), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). Image analysis showed Sn-Ag solder corroded and elevated Sn ion levels in tissue proximal to the solder compared to tissues more remote in all cases observed. The 316L SS exhibited signs of degradation with high surface concentrations of molybdenum and chromium and low iron compared to the parent alloy. Evidence of elevated iron, chromium and nickel within the tissues and storage solutions combined with precipitation of an iron-calcium-phosphorous material on some implants indicate evidence of SS corrosion. Ni-Ti, Pt-Ir and Dacron appear to have no major damage. This study includes preliminary results as part of the ongoing 522 study and therefore no final conclusions regarding the device or patient data can be drawn from this present study until the entire 522 study is complete. STATEMENT OF SIGNIFICANCE: The Essure Device is a female sterilization implant that was implanted into approximately 750,000 women. The device is composed of polyethylene terephthalate fibers and 4 metal alloys, 316L stainless steel, Nickel-Titanium, Tin-Silver and Platinum-Iridium. Following an increase in patient reported adverse events, the FDA required a 522-post market surveillance study. As part of this study, implants are retrieved from patients via salpingectomy or hysterectomy. This study focuses on the development of the implant retrieval methods following surgery, with focus on measuring local tissue metal ions, their distribution and assessing the degradation of the implant without correlation to patient clinical condition.

Pediatrician Explanations of Pediatric Pain in Clinical Settings: A Delicate Craft.

Explaining chronic pain to children and families can be challenging, particularly in the absence of an obvious physiologically identifiable cause for the child's pain. In addition to medical intervention, children and families may expect clinicians to provide clarity around the cause of pain. Such explanations are often provided by clinicians who have not received formal pain training. This qualitative study sought to explore the following question: What do pediatricians consider to be important when providing pain explanations to children and their parents? Using semistructured interview methods, 16 UK pediatricians were interviewed regarding their perceptions of explaining chronic pain to children and families in clinical settings. Data were analyzed using inductive reflexive thematic analysis. Analyses generated 3 themes: 1) timing of the explanation, 2) casting a wider net, and 3) tailoring of the narrative. Study findings demonstrated the need for pediatricians to skilfully interpret where children and families are in their pain journey and deliver an appropriate and adaptable explanation relating to individual needs. Analyses identified the importance of providing a pain explanation that could be repeated and understood by others outside the consultation room, to enable children and families to accept the explanation. PERSPECTIVE: Study findings identify the importance of language in addition to familial and broader factors that may influence the provision and adoption of chronic pain explanations provided by pediatricians to children and families. Improving pain explanation provision may influence treatment engagement for children and their parents, subsequently impacting pain related outcomes.

Predicting Corrosion Damage in the Human Body Using Artificial Intelligence: In Vitro Progress and Future Applications.

Artificial intelligence (AI) is used in the clinic to improve patient care. While the successes illustrate AI's impact, few studies have led to improved clinical outcomes. In this review, we focus on how AI models implemented in nonorthopedic fields of corrosion science may apply to the study of orthopedic alloys. We first define and introduce fundamental AI concepts and models, as well as physiologically relevant corrosion damage modes. We then systematically review the corrosion/AI literature. Finally, we identify several AI models that may be implemented to study fretting, crevice, and pitting corrosion of titanium and cobalt chrome alloys.