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Ecology of Hantaviruses in Rodent Reservoirs and Their Early Innate Immune Responses in Human Model Systems
Get PDFThe spillover of zoonotic RNA viruses is responsible for a great deal of the disease outbreaks in human populations. These spillover events are set to continue due to anthropogenic and environmental changes that impact the distribution of these viruses. The viruses in the family Hantaviridae are classified as one of these emerging zoonotic RNA viruses. The spillover of the viruses in this family are responsible for two severe human diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These viruses are distributed across the globe and are responsible for a large number of human disease cases with potentially high mortality rates each year. Unfortunately, there is a lack of surveillance efforts to identify hantaviruses in most countries making accurate diagnosis or recognition of hantavirus cases complicated. To address the potential public health impact of hantaviruses, we surveyed rodents in a rural region of Ukraine, and identified a high prevalence which underscores the potential for human disease in this country. As it is challenging to address how hantaviruses infect humans, I established approaches to evaluate the early innate immune response in primary lung microvascular endothelial cells (HLMVECs) with pathogenic and nonpathogenic hantaviruses. Surprisingly, my findings challenged some of the current dogma in that there were not dramatic difference between pathogenic and nonpathogenic viruses. This work highlights the critical need for advancement of cell culture models to probe the immune response.
To understand the ecology of hantaviruses in their reservoirs their prevalence was studied in northwestern Ukraine. A field capture study was conducted at two sites which each had distinct habitats and contained nine capture lines. During this survey, we captured 424 small mammals, consisting of species across three orders. The most abundant species were Myodes glareolus, the bank vole (45%); Apodemus flavicollis, the yellow-necked mouse (29%); and Apodemus agrarius, the striped field mouse (14.6%). Out of the collection, it was determined that 79 animals were seropositive by immunofluorescent assay (IFA), from which 15.7% were M. glareolus, 20.5% A. flavicollis, and 33.9% A. agrarius. These finding were of interest as M. glareolus and Apodemus spp. harbor Puumala orthohantavirus and Dobrava-Belgrade orthohantavirus viruses, respectively, which are responsible for causing HFRS in humans. IFA reciprocal titer showed a wide distribution indicating new infections are occurring. No relationship was found between species diversity and the proportion of hantavirus seropositive animals captured at these sites. Population analysis on M. glareolus and Apodemus spp. revealed that neither sex nor age was associated with being seropositive.
To define the early innate immune responses during human infection by hantaviruses, this research studies the responses in HLMVECs, the primary cells of infection in humans, infected by the pathogenic viruses, Andes orthohantavirus (ANDV) and Hantaan orthohantavirus (HTNV), and the nonpathogenic virus, Prospect Hill orthohantavirus (PHV). A curated list of 39 host genes were studied across multiple time points during the first 72 hours of infection of HLMVECs from a male donor by these three viruses. mRNA level analysis revealed the mRNA levels of only CCL5, CXCL10, CXCL11, IDO1, IFNB1, IRF7, and TLR3 we increased during infection of each viruses. The measurement of CCL5, CXCL10, CXCL11, IDO, and IFN-β secreted protein levels in the same HLMVEC donor during infection confirmed gene expression findings. The study of host immune responses to hantavirus infection was expanded to include HLMVECs from an additional male and two female donors. Measurement of secreted protein levels of CCL5, CXCL10, CXCL11, IDO, and IFN-β by each of the four donors revealed that levels of these proteins are upregulated during infection by each of the viruses. Pair wise analysis on these secreted protein levels by each of the donors during hantavirus infection suggests that donor characteristics and virus species together drive different outcomes. However, female donors had higher levels of CXCL10, IDO, and IFN-β and these increased protein levels were species specific. Lastly, the suppression of immune response involved in cell death were examined and it was found that ANDV is capable of inhibiting cell death in HLMVECs.
In summary, the findings presented, show the critical need to understand and define the early innate immune responses to hantaviral infection in human models as well as the necessity of understanding the ecology of hantaviruses in their reservoir hosts
Evolution of a Virtual Book Club: transforming workplace culture through book clubs
Get PDFObjective The objective of this project was to raise awareness of health/social topics by having meaningful conversations through virtual book club discussions. The goal is to address issues surrounding health disparities and diversity, equity, inclusion (DEI)concerns within the community.
Methods CME/Library team partnered with public library to select diverse health topics and books using NNLM Reading Club list. A plan was created to host multiple educational formats of virtual book club. The educational formats developed were (1) traditional virtual book club, (2) CME speaker in conjunction with book club, documentary screening, and panel discussion and (3) book club with physicians to add health education to discussions. In the planning process, the frequency of sessions and length of time was determined. Survey monkey and Zoom was used to collect registrations and evaluations.
Results Survey monkey results were collected for all sessions. All participates reported they had never participated in a book club activity before. A few of the participant comments included making an impact when you are not in a position to change policy, networking with one another in a safe environment, and increasing awareness of racial disparities in health care. Attendees were very impressed with film and panel discussion, commenting on frankness of conversation.
Conclusions Due to global pandemic and a season of social unrest, these educational formats provided were timely and beneficial to participants. Changing from in person to virtual proved to be a positive outcome for the library/CME team. The documentary screening and panel discussion that accompanied the speaker and book discussion added value to bringing awareness of health disparities. These virtual book clubs and speakers paved the way to having uncomfortable conversations in our organization. The library/CME team looks forward to partnering with experts and continuing virtual book clubs
Using Focus Groups to Gather Student Opinions on Medical Library Resources and Space
Get PDFOBJECTIVE
Medical education evolves with advancing technologies, and medical students are utilizing new learning methodologies in their curriculum. Medical educators can use student feedback to assess student study habits for modifications to current resources and spaces provided by the school. We obtained student opinions to identify student utilization issues of existing library space and learning resources at [School]
METHODS
We performed a literature review on focus group studies at other medical schools to guide the formulation of our groups. We invited all current medical students at [School] to participate in focus groups moderated by one author and recorded via Zoom teleconferencing. Performed an anonymous post-transcriptional analysis to collate participant opinions with significant statements into general feedback themes from group discussions.
RESULTS
Twenty-one students participated in one of three separate focus groups of 6 to 9 students each. Feedback obtained was categorized into two major themes. The first included modifying the curriculum learning guide to include referenced page numbers and chapter titles, more efficient checkout of books, more concise resource materials, and acquiring new third-party question bank resources. The second theme of library physical facility issues included adding electrical outlets at study tables, getting better chairs for seating, getting a new printer, and adding study rooms or cubicles for more private studying.
CONCLUSION
Focus groups to gather medical student opinions proved to be an effective strategy to obtain feedback on current resource and space issues. In addition, the group dynamic permitted an open discussion among students with opportunities to interact with one another in creating and refining suggestions. The results from this study have helped [School] faculty to make modifications enhancing student education
The Use of DMAIC to Improve Quality Vaccination Recommendations in Chain Community Pharmacies
Get PDFCommunity pharmacies provide the convenience and ease of administrating vaccinations outside traditional settings. Vaccinations are health initiatives that protect communities and improve health outcomes in all populations. Despite their accessibility and supporting clinical data, various influential factors contribute to the current suboptimal rates of vaccine administration. Given the common barriers to vaccine administration, this research narrows down to address a specific barrier and attempts to implement a method that focuses on improving vaccine rates in community pharmacies. This research is a case study that utilizes the DMAIC model of lean six sigma and aims to use this quality improvement process to identify, measure, analyze, and implement a training program to facilitate pharmacists in high-quality vaccine recommendations to promote higher rates of pneumococcal vaccinations in community settings
Antibiotic Tolerance and Heteroresistance: Associated Fitness Costs and Potential in Evading Antibiotic Killing
Get PDFStreptococcus pneumoniae is a prominent human pathogen that causes both invasive and non-invasive diseases, such as otitis media, pneumonia, meningitis, and bacteremia. Although it is frequently an asymptomatic colonizer of the human nasopharynx, S. pneumoniae is a major cause of morbidity and mortality in the immune compromised population, young children, and the elderly. Up until the 1970s, S. pneumoniae was susceptible to almost all antibiotics. Since then, this pathogen has gained resistance to a variety of antibiotic treatments, including beta-lactams, macrolides, and fluoroquinolones.
In the first chapter, we focused on fluoroquinolone resistance in S. pneumoniae. Fluoroquinolones are one of the most frequently prescribed antibiotics, yet fluoroquinolone resistance in S. pneumoniae is still rare compared to other antibiotics resistance, such as beta-lactams. In this study, we investigated the mechanism(s) underlying this intriguing case by assessing the efficiency and fitness costs of horizontal transfer of fluoroquinolone resistance determinants. We hypothesized that the fitness tradeoffs incurred by resistance determinants would define the likelihood of such resistance to emerge in a clinical setting. Clinically relevant fluoroquinolone resistance requires both on-target mutations in topoisomerase IV parC and DNA gyrase gyrA. The wild-type S. pneumoniae TIGR4 was not readily transformed with single mutations in gyrA or parC; however, it was readily transformed with double on-target mutations in gyrA and parC. Compared to the wild type, the single on-target mutants were attenuated, whereas the double on-target mutant was virulent. This suggests that clinically relevant, high-level fluoroquinolone resistance requires the combination of several on-target mutations, which could be acquired via horizontal transfer. The combination of the extremely low probability of acquiring two or more mutations simultaneously from different target genes and the deleterious fitness tradeoffs imposed by individual on-target mutations in gyrA or parC likely result in the infrequent prevalence of fluoroquinolone resistance in S. pneumoniae. Through in vitro serial passaging, we identified a novel mutation (N291D) in the efflux pump patA that facilitated the acquisition of the on-target mutations in parC and gyrA via horizontal transfer with minimal fitness tradeoffs. We also modeled the evolution of fluoroquinolone resistance in a murine host and identified mutation(s) that arose and fixated during in vivo passaging. Interestingly, the experimentally-evolved isolates from the in vivo passaging study did not encode on-target mutations for fluoroquinolone resistance and instead displayed tolerance, which potentially facilitated the subsequent acquisition of fluoroquinolone resistance.
In the next chapter, we investigated how fitness tradeoffs and horizontal transfer play a role in the emergence and spread of another mainstay of treatment of pneumococcal infection, beta-lactams- specifically, penicillin, which inhibit wall synthesis. We found that recombination with related viridans species via horizontal transfer may be preferable to de novo on-target mutations in penicillin-binding proteins in S. pneumoniae to acquire resistance more rapidly without initially losing in vivo fitness. Initial recombinants retained virulence in vivo and could readily acquire higher resistance via subsequent transformation. The final recombinants displayed tolerance to penicillin, having reduced kill kinetics compared to the wild type. This suggests that S. pneumoniae might have minimized fitness tradeoffs by developing tolerance via horizonal transfer with related viridans group streptococci, which would serve as a stepping stone for subsequent development of resistance.
In the next study, we explored an underlying mechanism of antibiotic tolerance in S. pneumoniae. In our model of the evolution of antibiotic resistance, rny that encodes ribonuclease Y (RNAse Y) was a mutational hotspot across multiple antibiotics. The rny knockout mutant was fully virulent, indicating that deletion of this gene imposed minimal to no fitness tradeoffs. Disruptions in RNA degradation resulted in tolerance to several classes of antibiotics and reduced antibiotic treatment efficacy in vivo.
In the final chapter, we investigated whether other phenomena that allow bacteria to withstand antibiotic killing, such as heteroresistance, can affect antibiotic treatment outcomes clinically. We found that vancomycin heteroresistance is associated with treatment failure and poor outcomes in coagulase-negative staphylococci (CoNS) from pediatric leukemia patients.
Taken together, this dissertation provides insights into strategies of S. pneumoniae for striking a balance between maximizing resistance potential while minimizing fitness tradeoffs, thereby potentially contributing to the development of more-effective antibiotics for treatment of pneumococcal disease. It also provided insights into the association between heteroresistance in CoNS and clinical outcomes
Near-Field Electrospinning and Characterization of Biodegradable Small Diameter Vascular Grafts
Get PDFThe ideal “off the shelf” tissue engineering, small-diameter (\u3c 6 mm inner diameter (ID)) vascular graft hinges on designing a template that facilitates transmural ingrowth of capillaries to regenerate an endothelized neointimal surface. Previous traditionally electrospun (TES) approaches to create bioresorbable vascular grafts lack the pore sizes required to facilitate transmural capillary ingrowth required for successful in situ neovascular regeneration. Therefore, the ability to create scaffolds with program-specific architectures independent of fiber diameter via the relatively recent sub-technique of near-field electrospinning (NFES) represents a promising solution to create tissue engineering vascular grafts. These programmed large pore sizes are anticipated to promote in situ regeneration and improve the outcomes as well as the quality of life of patients with arterial disease.
In this dissertation, we manufactured via NFES as well as characterized biodegradable polydioxanone (PDO) small-diameter vascular grafts. Chapter 1 introduces the need for off-the-shelf, small-diameter vascular grafts to facilitate in situ regeneration, the process and pore size limitations of TES vascular grafts, and the promising use of NFES to develop precisely tailored PDO vascular grafts. Chapter 2 describes the process of NFES and details the current progress in NFES of biomedical polymers as well as the major limitations that exist in the field. Chapters 3, 4, and 5 contain primary research exploring the creation of an NFES vascular graft scaffold and characterizing the mechanical as well as biological response of these scaffolds. Specifically, in Chapter 3 we demonstrate a NFES apparatus designed around a commercial 3D printer to write PDO microfibers. The processing parameters of air gap, polymer concentration, translational velocity, needle gauge, and applied voltage were characterized for their effects on PDO fiber diameter. The processing parameters of polymer concentration and translational fiber deposition velocity were further characterized for their effects on fiber crystallinity and individual fiber uniformity. The precision of fiber stacking via a 3D printer was qualitatively evaluated to inform the creation of 3D scaffolds to guide the alignment of human gingival fibroblasts. It was found that fiber diameters correlate positively with polymer concentration, applied voltage, and needle gauge and inversely correlate with translational velocity and air gap distance. Individual fiber diameter variability decreases, and crystallinity increases with increasing translational fiber deposition velocity. These data resulted in the creation of tailored PDO 3D scaffolds which guided the alignment of primary human fibroblast cells. Together, these results suggest that NFES of PDO can be scaled to create precise geometries with tailored fiber diameters for vascular graft scaffolds.
In Chapter 4, we demonstrated a NFES device to semi-stably write PDO microfibers. The polymer spinneret was programmed to translate in a stacking grid pattern, which resulted in a scaffold with highly aligned grid fibers that were intercalated with low density, random fibers. As a consequence of this random switching process, increasing the grid dimensions resulted in both a lower density of fibers in the center of each grid in the scaffold as well as a lower density of “rebar-like” stacked fibers per unit area. These hybrid architecture scaffolds resulted in tailorable as well as greater surface pore sizes as given by scanning electron micrographs and effective object permeability as indicated by fluorescent microsphere filtration compared to TES scaffolds of the same fiber diameter. Furthermore, these programmable scaffolds resulted in tailorability in the characterized mechanical properties ultimate tensile strength, percent elongation, yield stress, yield elongation, and Young’s modulus independent of fiber diameter compared to the static TES scaffold characterization. Lastly, the innate immune response of neutrophil extracellular traps (NETs) was further attenuated on NFES scaffolds compared to TES scaffolds. These results suggest that this novel NFES scaffold architecture of PDO can be highly tailored as a function of programming for small diameter vascular graft scaffolds.
In Chapter 5, we created two types of NFES PDO architectures, as small-diameter vascular graft scaffolds. The first architecture type consisted of a 200 x 200 µm and 500 x 500 µm grid geometry with random fiber infill produced from one set of processing parameters, while the second architecture consisted of aligned fibers written in a 45°/45° and 20°/70° offset from the long axis, both on a 4 mm diameter cylindrical mandrel. These vascular graft scaffolds were characterized for their effective object transit pore size, mechanical properties, and platelet-material interactions compared to TES scaffolds and Gore-Tex® vascular grafts. It was found that effective pore size, given by 9.9 and 97 µm microsphere filtration through the scaffold wall for NFES grafts, was significantly more permeable compared to TES grafts and Gore-Tex® vascular grafts. Furthermore, the characterized mechanical properties of ultimate tensile strength, percent elongation, suture retention, burst pressure, and Young’s modulus were all tailorable for NFES grafts, independent of fiber diameter, compared to TES graft characterization. Lastly, platelet adhesion was attenuated on large pore size NFES grafts compared to the TES grafts which approximated the low level of platelet adhesion measured on Gore-Tex® grafts, with all grafts showing minimal platelet activation given by P-selectin surface expression. Together, these results suggest a highly tailorable process for the creation of the next generation of small-diameter vascular grafts.
Lastly, Chapter 6 expounds future considerations for continuing research in NFES technology, NFES for general tissue engineering, and NFES for vascular tissue engineering as well as gives final conclusions. Together, the finding of this dissertation indicated that NFES vascular grafts result in seamless, small diameter tubular scaffolds with programmable pore sizes on the magnitude anticipated to facilitate transmural endothelialization as well as programmable mechanical properties that approximate native values. Thus, this work represents the next step in developing bioinstructive designed scaffolds to facilitate in situ vascular regeneration to improve the outcomes as well as the quality of life of patients with arterial vascular disease
Analyzing point of care tools through faculty, resident, and stakeholder buy-in: a cautionary tale
Get PDFPurpose: Costs for Preston Medical Library’s primary point-of-care (POC) clinical tool have increased to half of the acquisitions budget, while user affiliation data have not been provided to facilitate cost sharing. In response, user preferences for POC tools were analyzed to determine a viable, less expensive alternative to the current subscription.
Setting/Participants/Resources: Faculty and residents at the University of Tennessee Graduate School of Medicine (GSM), and other clinical staff at the University of Tennessee Medical Center (UTMC), a 685-bed teaching hospital.
Methodology: At the direction of school leadership, a working group of library staff, resident physicians, and medical faculty members was appointed, and data were gathered through individual user surveys of clinical support tools. Three POC tool options were considered. Select clinicians evaluated the tools using a series of questions individually chosen as typical to their disciplines. Additionally, feedback was sought from other AAHSL institutions regarding subscriptions to the tool in question and funding schemes. At the same time, the Dean communicated to the medical campus community that cost increases for the product had become prohibitive, requiring consideration of alternatives.
Results/Outcomes: Survey responses revealed a strong preference for the incumbent tool, rating PubMed as the second preferred source, but not substitutable. Working group members preferred the current product at POC, judging one of the candidate tools as “adequate” but less user friendly and more time consuming to access. Hospital leadership also received responses from clinical staff. As a result, a cost sharing agreement with the school was forged.
Discussion/Conclusion: A deliberative approach to assessing POC clinical tools was used, resulting in continued access to the preferred product. Enhanced data gathering on a go-forward basis will help to ascertain use patterns by academic and hospital users. The library and the other stakeholders will monitor development of alternative POC tools and costs for future decision making
Feasibility and Acceptability of Using Mobile Health Apps in Underserved Patients with Diabetes
Get PDFIntroduction. Diabetes mellitus is a condition with a growing morbidity and mortality burden. An estimated 30 million adults currently live with diabetes, with each individual spending over $9500 annually on medical care. The successful management of diabetes is a lifelong endeavor. This involves balancing a variety of factors including diet, medications, and glucose monitoring. It has been well established that successful control of diabetes depends largely upon patients’ daily lifestyle habits and activities. Not all patients, however, have the resources necessary for effective diabetes management. Health disparities lead to a higher rate of diabetes development in minority and poor populations. Since underserved patients have limited access to traditional healthcare avenues, providers should explore other means, like mobile health (mHealth), to help such patients. The rapid adoption of smartphones within the last decade has allowed an opportunity for patients to use mHealth and smartphone applications (apps) as a low-cost way to get health information and services. mHealth has the potential to address such disparities in access to health care. Little is known about the effectiveness of using apps to help underserved patients with their diabetes management. Assessing these patients’ current self-management practices and their interest in using smartphone apps for their diabetes management is the first step in determining how mHealth may benefit this patient population.
Purpose. The purpose of this study was to assess how underserved patients with limited access to primary care physicians handled their diabetes on their own at home, to determine what challenges they faced with their self-management, and to examine their willingness to use diabetes mHealth apps on their smartphones to assist with their diabetes management.
Methods. This study employed purposive sampling to select patients for individual interviews. Participant selection occurred at a Memphis hospital located in an area of town with predominately low-income and minority residents, as well as a high prevalence of diabetes. Semi-structured interviews were conducted on-site at the hospital based on McNamara’s interview staging. In all, 15 interviews were recorded, transcribed, and coded according to the interpretative phenomenological analysis framework.
Results. The data produced 5 topic clusters related to at-home diabetes management, which supported 2 overarching themes, and 7 clusters related to mHealth smartphone app use, which supported 3 overarching themes. The themes related to self-management are as follows: 1. Patients are aware that successful diabetes control requires active engagement on their part but voiced struggles related to balancing limited income and a healthy diet, how to manage fluctuating glucose readings throughout the day, and affording medications; and 2. Lacking a traditional relationship with a primary care doctor, these underserved patients turn to friends and family, written materials, and the internet as health care resources. The themes related to smartphone mHealth are as follows: 1. Despite limited knowledge about health apps and varying phone use patterns, patients were all willing to try at least one diabetes-related app; 2. App functions should be individualized to meet each patient’s needs for maximum benefit; and 3. Barriers to app use were varied but commonly included knowledge and technological challenges and security issues.
Conclusion. Interviews from this vulnerable population demonstrated that individuals understood the importance of their own active involvement in controlling their diabetes. Yet, because of limited economic and health care resources, these patients struggle with the implementation of effective lifestyle choices in their daily routine. Furthermore, interviewees expressed interest in trying mobile health apps for diabetes management, despite minimal knowledge about the technology. Responses showed that selecting apps tailored to each individual’s needs, instead of offering one blanket multifunctional app, would provide patients with the greatest benefit. Smartphone apps may be a low-cost health resource that patients without regular access to physicians can use for their at-home diabetes management
Transversus Abdominis Plane Block: A Scoping Review
Get PDFThe purpose of this project is to provide an overview of the literature on the analgesic effects of transverse abdominal plane (TAP) block and its effectiveness in reducing opioid consumption
Iatrogenic Electrocautery Damage and Cellular-Based Corrosion of Total Joint Arthroplasty Biomaterials
Get PDFIntroduction. The number of patients undergoing a Primary Total Knee Arthroplasty (PTKA) has been increasing steadily each year. Of those PTKA patients, 20% report long-term pain and/or some functional deficit. Cobalt-Chromium-Molybdenum (CoCrMo) alloy is one of the most used materials in Total Joint Arthroplasty (TJA) implants due the material’s high strength, high corrosion resistance, and biocompatibility. The release of metal ions and potential occurrence of metallosis in TJA has been shown to be detrimental to the longevity of the implant. The mechanisms leading to this increase in metal ion concentrations have been up for debate, with some believing it is caused by Electrocautery (EC) damage at the time of surgery and others believing it is caused by inflammatory cells attacking the implant surface. The purpose of this thesis is to identify to what degree Electrocautery damage can alter the implant surface and if inflammatory cells are able to alter the implant surface and ingest metal particles.
Methodology. To better understand how EC damage can alter implant surfaces, three different types of femoral component bearing surfaces were selected and intentionally damaged in the operating room using the plasma arc from both monopolar (MP) (Bovie) and Bipolar (BP) (Aquamantys) sources. MP and BP EC damage was done at varying power levels using a 3-second hover method 3 mm from the implant surface. Scanning electron microscopy (SEM) (Zeiss, Oberkochen, Germany) was used to obtain a detailed microscopic analysis of the damaged areas. Energy-dispersive X-ray spectrometry (EDS) (Oxford, High Wycombe, UK) was utilized to assess the elements present in pits found in the corroded areas. Surface Topography was analyzed using a profilometer (DektakXT; Bruker, Tucson, AZ) in the central portion of the damaged area for each MP and BP energy setting. Each damaged area was evaluated with the aid of TalyMap (Mountains software; Digital Surf, Besançon, France) using ISO 4287 measurements for Arithmetic Average height (Ra), Kurtosis (Rk), Heighest Peak to Lowest Valley (Rz), and Skewness (Rsk). SEM, EDS, and Surface Topography were also used to look at undamaged areas of the implants.
In a separate experiment, IC-21 ATCC murine peritoneal macrophages were cultured with RPMI 1640 growth medium of supplemented with 10% fetal bovine serum (FBS), L-glutamine, and gentamicin. Select groups of cells were then activated using Interferon Gamma (IFNγ) and Lipopolysaccharide (LPS). CoCrMo alloy disks were cut, polished, passivated, and placed into 96 well plates and a select number intentionally damaged in the operating room with a MP EC device. After the cells were allowed to attach to the surface for 24 hours, culture medium was replaced every 12 hours and supernatant fluid was collected every 4 days starting on the second day of the experiment. After 30 days, cells were removed from the surface, counted and digested. The metal concentrations found in the supernatant and digested cell mixture were assessed using inductively coupled plasma spectrometry (ICP-MS), conducted at Brooks Applied Labs (Bothwell, WA). Statistical analysis was conducted using SigmaPlot (Systat Software, Chicago, IL) and Microsoft Excel (Microsoft, Redmond, WA).
Results. Surface Profilometry quantified the topographical changes due to the damage form the MP and BP EC devices. The median Ra and Rz measurements were larger for the BP damaged areas compared to the MP for all bearing surfaces. The Oxinium surface displayed the greatest increase in roughness parameters compared to the undamaged regions. The CoCr surface displayed the greatest Rsk for the BP damaged areas. The ZrN had the smallest differences in Rz and Ra for both MP and BP damage areas compared to undamaged areas. SEM imaging displayed pitting in the regions intentionally damage with a MP or BP EC device. Backscatter EDS analysis found significant changes in the elemental profile for the BP damage compared to the MP damage.
Cellular corrosion of the CoCr disks was quantified by measuring the concentration of Co, Cr, and Mo in the supernatant fluid collected off of the culture over the course of the 30-day experiment. The Co supernatant concentration was higher in the Undamaged Disks with Activated Cells versus its control which contained medium with no cells. The Cr concentration was higher in the supernatant fluid of the EC Damaged Disks with Standard Cells versus its control which contained medium with no cells. Between experimental groups, higher concentrations of Co and Mo was found in the supernatant of the Undamaged Disks with Standard Cells versus the EC Damaged Disks with Standard Cells. There was also a higher Co supernatant metal concentration when comparing the Undamaged Disks with Activated Cells versus the EC Damaged Disks with Activated Cells. A higher Cr supernatant metal concentration was found in the EC Damaged Disks with Activated Cells versus the EC Damaged Disks with Standard Cells. Following the end of the 30-day experiment, cells were digested to determine their inner metal ion concentration. There was a significantly higher intracellular Co and Mo concentration in the Undamaged Disks with Activated Cells versus the Undamaged Disks with Standard Cells. As well as a higher intracellular Co concentration in the EC Damaged Disks with Activated Cells versus the EC Damaged Disks with Standard Cells. SEM imaging displayed microscopic pitting on the surface exposed to macrophages and EC damage. Backscatter EDS analysis found significant differences in the elemental concentration of Carbon, Oxygen, Iron and Nickel between the experimental groups. From the EDS Backscatter analysis, the disks with EC damage displayed a higher Fe/C ratio compared to the undamaged disks. Showing evidence that EC damage alters the chemical profile of the CoCr disk surface