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Interface engineering and mechanics in haptics and additive manufacturing
No full textDhong, CharlesKorley, LaShanda T.J.The properties and mechanics of interfaces can control a material system’s engineering performance, from the object-finger interface in haptic materials to the interfaces created between tracks in additive manufacturing. These interfaces dictate the tactile perception of an object and the performance of 3D printed parts. By engineering material surfaces to control friction at the object-finger interface, we can change how an object feels. By designing material and process techniques with tailored operating parameters, we can build more advanced material structures. Identifying the mechanics at these interfaces is essential in closing existing gaps to engineer materials with greater performance, reliability, and scope. ☐ The object-finger interface, through friction and adhesion, generates the stimuli behind human touch perception. However, this interface is poorly understood due to its dynamic nature and contact of soft objects. As such, a knowledge gap is presented for practical implementation, such as advancement of tactile aids for people who are visually impaired or blind. Here, surface chemistry modification of everyday objects is achieved by coating two different colored objects with chemically distinct silane precursors. Mechanical friction characterization is performed on each surface, and analysis of these friction signals is presented as a predictor for distinct tactile perception. Congenitally blind human testing participants are able to reliably distinguish the different colored objects by touch alone, in a demonstration of surface chemistry modification as a practical tactile aid. Translating this work into more widely used polymer platforms, a polystyrene solution is selectively spray-coated onto textured surfaces as a method of durable and scalable application of chemical features onto traditional physical surface features. Morphological control of a poly(styrene)-b- poly(ethylene oxide) block copolymer coating is investigated as an additional modality of surface design. Phase-separation of the block copolymer film presents a chemically nanopatterned surface, distinct to that of a disordered film. The methods described here again undergo human testing and provide the necessary insight to design haptic cues based on microstructural control of interfaces with material chemistry. ☐ Finally, several instruments and processing methods are developed to address existing obstacles in material extrusion additive manufacturing. A novel material delivery system is developed which bypasses the current material limiting step of filament feedstock, greatly expanding the variety of materials available to the process. A second novel instrument is developed for in-process coextrusion of materials. It produces a coaxial composite core-shell track morphology, which can be directly varied during manufacturing to tune material properties throughout an object. Thermorheological modeling of a track interface provides insight for material and parametric design in order to approach bulk material properties. Additional material and process techniques are included to highlight other areas of track interface engineering. These tools and techniques create stronger parts out of more materials, and significantly progress the process from its current technological state. ☐ The work presented here shows how interfaces can dictate ultimate performance, whether for the dynamic object-finger interface or fused material interfaces. The results advance the state of interface and material engineering in the fields of haptics and additive manufacturing.University of Delaware, Department of Materials Science and EngineeringPh.D
Lymph node as Cerberus: the study and simulation of HIV drug exclusion
No full textZurakowski, Ryan M.Gleghorn, Jason P.Combination Antiretroviral Therapy (cART) has effectively suppressed HIV replication in most infected individuals over the past two decades. However, cART cannot eradicate the virus, requiring patients to maintain lifelong adherence to the drug regimen to prevent viral rebound. Recent studies have revealed heterogeneous distribution of cART drugs in certain tissues, particularly lymphatic organs such as lymph nodes. Our previous work demonstrates that drug exclusion from these sites can create pharmacological sanctuaries within lymph nodes, potentially hindering HIV treatment efficacy. Understanding the mechanisms of drug exclusion in lymph nodes is crucial for developing more effective therapies for HIV and other diseases, including cancer. This dissertation presents a novel approach to solving pharmacokinetic (PK) reaction-diffusion equations on an anatomically accurate three-dimensional (3D) murine lymph node using the Finite Volume Method (FVM) for several cART drugs. This marks the first instance of PK dynamics being solved on the exact geometry of an anatomically reconstructed lymph node. Our modeling tool enables comprehensive sensitivity analyses to determine the relationship between between drug transport characteristics and lymph node penetration. Ultimately, this research provides a powerful framework for enhancing drug design, potentially leading to more effective treatments for HIV and related conditions.University of Delaware, Center for Bioinformatics and Computational BiologyPh.D
Beyond pleasurable and meaningful: Psychologically rich entertainment experiences
No full textThis article was originally published in PLoS ONE. The version of record is available at: https://doi.org/10.1371/journal.pone.0315596.
© 2025 Wirz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Entertainment experiences have been conceptualized as hedonic (pleasurable) or eudaimonic (meaningful), mirroring the hedonic and eudaimonic components of psychological well-being. However, psychologists have proposed a third component of well-being: psychological richness, which is characterized by variety, novelty, and interest. In this paper we explore the role of psychological richness in film and television entertainment experiences. Two studies, an experience sampling study (n = 28) and a survey (students in the US, n = 247 and general population in Germany, n = 289) show the prevalence of experience of psychological richness during media use and its positive relationship with well-being. A replication with a different scale (n = 291) demonstrates that psychologically rich entertainment experiences may have been previously been conflated by some measures of eudaimonic entertainment. Incorporating psychologically rich entertainment experiences as a third addition to hedonic and eudaimonic experiences can increase the intervention potential of media used to enhance well-being.The author(s) received no specific funding for this work
The role of the transcription elongation factor Ell2 in gene expression control during lens development
No full textLachke, Salil A.The vertebrate eye is a multicomponent organ in which transparent tissues namely, the cornea and the lens, together refract and focus light on the retina to enable high-resolution vision. Formation of the mammalian eye is a complex process involving coordinate development of tissues. Perturbation of this process can cause ocular birth defects including microphthalmia (small eye), anophthalmia (absence of eye), or abnormalities in specific eye tissues, such as congenital cataract (defined as loss of lens transparency). To understand the pathology of ocular developmental defects, it is critical to identify key regulatory genes that play an important role in the developing eye, and to define their relationships with other factors in the form of networks. ☐ The lens comprises two principal cell types, the anteriorly localized epithelial cells, which differentiate posteriorly into fiber cells that make up the bulk of the tissue. Thus far, several genes involved in control of lens development have been identified and their deficiency or mutation has been associated with lens defects or congenital cataract. These include regulatory molecules such as members of signaling pathways (e.g., FGF, BMP etc.), transcription factors (TFs) (e.g., Pax6, Prox1, c-Maf, Sox1 etc.) and post-transcriptional regulatory RNA-binding proteins (e.g., Celf1, Tdrd7, Caprin2, Rbm24, etc.) – all distinct regulatory mechanisms that together determine the proteome–have been characterized. ☐ In the lens, the fiber gene expression is programmed toward building massive upregulation of select fiber cell expressed mRNAs (e.g., crystallins, membrane proteins, fibroblast growth factor receptors, etc.) and their subsequent translation into high amounts of proteins as they migrate towards the lens center and undergo terminal differentiation and lose organelles, which are essential for lens transparency. Therefore, fiber cells have the added challenge of achieving the proper transcript dosage prior to organelle/nuclear degradation. In human lenses, the concentration of crystallins can exceed 450 mg/ml. Presently, optimally high transcription of crystallins and other key lens genes is attributed to clusters of binding sites for specific groups of TFs (e.g., Sox1, c-Maf, Prox1, Pax6) in their promoter and/or enhancer region(s) that facilitates the formation of transcriptional complexes and thereby effectively initiate and regulate high levels of transcription. ☐ However, an unanswered fundamental question in lens research is whether our current understanding of lens transcription factors and the combinatorial control they exert on their target genes is sufficient to explain the extreme abundance of specific transcripts (e.g., crystallins) in fiber cells, or are there are other regulatory “general” transcription regulatory mechanisms that are necessary for achieving the specialized lens transcriptome? For example, are the regulators that control the ubiquitously important “transcription elongation” process specifically recruited for achieving proper dosage/levels of select highly expressed transcripts in development, particularly in the lens? My dissertation has addressed this key knowledge-gap and my new research findings hold a potential to have an broader impact, beyond lens development, on the mechanisms of gene expression control in other cells/tissue. ☐ I applied the bioinformatics tool termed iSyTE (integrated Systems Tool for Eye gene discovery) to identify the transcription elongation factor Ell2 (Elongation factor for RNA Polymerase II 2) (OMIM: 601874), based on its high absolute expression and high enriched expression in the mouse lens. Ell2 encodes a transcription elongation factor containing ELL domain and an occludin homology domain that allow interactions with RNA polymerase II (RNA Pol II) and other proteins of a large macromolecular protein complex called the super elongation complex (SEC). After transcription initiation, RNA Pol II transcribes between 30-80 nucleotides and then “pauses” because of the activity of two proteins, the negative elongation factor (NELF) and the DRB-sensitivity inducing transcriptional factor (DSIF). This “pause” must be relieved by SEC which contains positive transcription elongation factor b (P-TEFb) and an Ell family protein (e.g., at least one of Ell, Ell2, Ell3). Additionally, Ell2 prevents the backtracking of RNA pol II by keeping 3’OH of the nascent RNA aligned with the RNA Pol II catalytic site. Thus, Ell2 is important in control of transcription. ☐ To investigate the role of Ell2 in the lens, I first validated iSyTE’s prediction that Ell2 is expressed on both RNA and protein levels in mouse lens development by in situ hybridization (ISH) and immunofluorescence (IF), respectively. ISH shows that Ell2 mRNA is highly abundant in the lens transition zone (tz) and in fiber cells in early development. In agreement, IF assays show Ell2 protein is robustly present in tz and fiber cells at embryonic and early postnatal stages, and in later postnatal stages is also expressed in lens epithelial cells suggesting that Ell2 has temporal- and cell type-specific roles. Next, to gain insight into the impact of Ell2 deficiency in an autonomous manner in the lens, I generated lens-specific conditional Ell2 knockout mouse (termed Ell2cKO) using the Pax6GFPCre transgenic mouse line where Cre recombinase is expressed at embryonic day (E) 9.5 in lens placode formation. Lens-specific Ell2 KO in the Ell2cKO mice was confirmed on the gene, RNA and protein levels. ☐ I next performed phenotypic characterization of Ell2cKO mouse lenses. Light microscopy and grid imaging shows that Ell2cKO mice exhibit reduced sized lenses early in life starting from stage postnatal day (P) 15, and being fully penetrant with age after stage postnatal day (P) 30. Further, Ell2-deficient lenses exhibit abnormalities in lens shape and refractive properties and histological analysis by H&E shows lens tissue abnormalities. However, staining with a marker for proliferation, Ki-67, showed no appreciable differences between control and Ell2cKO lenses, suggesting that the observed lens defects were not due to changes in proliferation. ☐ To examine global gene expression changes associated with Ell2-deficiency-based lens defects, I performed bulk RNA-seq on Ell2cKO lenses at P30, when the lens defects are fully penetrant. RNA-seq analysis of Ell2cKO lenses at P30 identified 982 differentially expressed genes (DEGs). Of these DEGs, 457 were reduced, and 525 were elevated in Ell2cKO lenses. Cluster analysis of these DEGs using the Database for Annotation, Visualization, and Integrated Discovery (DAVID v6 .8) for functional annotation by gene ontology (GO) categories identifies GO categories that are relevant to vision and lens development. This suggests that deletion of Ell2 causes the misexpression of key genes that are involved in normal lens development. ☐ Interestingly, among the DEGs, several candidates are linked to lens development or cataract in animal models or in humans. Namely, genes exhibiting high expression in normal fiber cells, such as crystallins (e.g., Cryga, Crygf, Cryba1, Crybb1), Aqp0 (Mip), etc., as well as those exhibiting high expression in epithelial cells, (e.g., Aqp1), etc., are reduced in Ell2cKO lenses. These data indicate that Ell2 is necessary for optimal transcript levels of key genes in fiber cells and/or epithelial cells – a role perhaps made necessary as, particularly in the fiber cells, specific transcripts not only need to be made abundantly, but they need to achieve these high levels prior to nuclear and organelle degradation in fiber cell maturation, failure of which causes lens defects. However, some genes highly expressed in fiber cells (e.g., Ezr, Gja3, Gja8, Hspb1, Tdrd7) remain unaffected, suggesting that Ell2 functions in the specific upregulation of a subset of genes in the lens. Also, importantly, the key transcription factors (TFs) Maf (c-Maf), Prox1, and Sox1, which have been previously shown to be involved in fiber gene expression (e.g., crystallins) are unaltered in Ell2cKO lenses suggesting that the misexpression of fiber cell genes is not simply due to changes in the expression of these lens TFs, but likely a direct result of loss of Ell2. RT-qPCR showed a significant reduction of Crybb1, Cryge, Mip, Lgsn, Birc7, and Hmox1 transcripts in Ell2cKO lenses, thus offering independent validation of DEGs identified by RNA-seq in Ell2cKO lenses. ☐ In addition to bulk RNA-seq, I performed single nucleus (sn) multiome analysis (snRNA-seq and snATAC-seq (assay for transposase-accessible chromatin using sequencing)) on P10 and P15 Ell2cKO lenses to gain insight into spatiotemporal gene expression in lens development on the single cell-level (represented by single nucleus), and to examine how it is impacted by loss of Ell2. snRNA-seq identified alterations in gene expression in the epithelial, intermediate and fiber populations in Ell2cKO lenses. The snRNA-seq analysis reveals a significant reduction in the expression of several cohorts of crystallin genes, including Cryaa, Cryba1, Cryba2, Crybb2, Cryga, Crygf, Cryge, Crygd, Crygc, Crygb, Crygs and many other lens expressed genes in Ell2cKO lens cell populations. These data are consistent with bulk RNA-seq data, thus offering independent validation. ☐ Further, to examine if Ell2 loss results in alteration of the lens chromatin and to understand how this correlates with transcriptional changes, I performed snATAC-seq. Overall, the comparison of snRNA-seq and snATAC-seq data showed correlation between chromatin accessibility changes and RNA levels changes in Ell2cKO lens. In detailed analysis focusing on specific genes, snATAC-seq identified specific alterations in chromatin accessibility in distinct cell populations in Ell2cKO lenses. For example, in Ell2cKO lenses, snATAC-seq showed reduced promoter accessibility across loci for Cryge, specifically in the lens cell population termed as “intermediate cluster”, which can be considered as that representative of cells that are in the transition zone or are in early differentiating stages. Interestingly, in cell clusters that represent later stages of differentiating fiber cells, the promoter accessibility for Cryge was similar between control and Ell2cKO lenses. However, on the RNA level, in both cell populations Cryge mRNAs were found to be reduced in Ell2cKO lens. These data suggest that Ell2 is critically necessary – in transition zone cells or in early differentiating fiber cells – for achieving optimal chromatin accessibility and RNA abundance at specific genic loci. Furthermore, these data show that in the absence of Ell2, even if the chromatin accessibility is re-gained, as in later stages of fiber cells, the RNA abundance levels cannot be recovered to normal and remain overall reduced. Together, these data, based on single nucleus multiomics analysis, uncover the requirement of Ell2 in a critical early phase of fiber differentiation, perhaps correlating with a critical spatiotemporal window when there is optimal stochiometric levels of the transcription factors (e.g., Pax6, c-Maf, Prox1, Sox1) for achieving optimal transcriptome. ☐ To determine Ell2’s preferential localization to lens genomic loci, I performed chromatin immunoprecipitation (ChIP) in wild type (WT) lenses using Ell2 antibody followed by genomic DNA PCR which demonstrates that Ell2 protein is enriched in Cryge and Crygf gene loci within 100-150 bp from the transcriptional start (TSS). Together, these data (snRNA-seq, snATAC-seq, ChIP-PCR) help define Ell2’s selective role in regulation of genes important in lens development and cataract. ☐ To gain insights into the regulation of Ell2 itself, I analyzed RNA-seq data generated on lenses deficient for the RNA-binding protein (RBP) encoding genes Celf1 or Elavl1, which are linked to lens defects and cataract. This analysis shows that Ell2 mRNA is mis-expressed in Celf1cKO and Elavl1cKO lenses, suggesting that post-transcriptional regulatory mechanisms have evolved to ensure that Ell2 mRNA levels are optimally controlled in the lens. These data also suggest a potential cross-talk between transcriptional and post-transcriptional networks in the lens. ☐ In sum, I utilized a rigorous multi-disciplinary approach using the tools of genetics, cell biology and state-of-the-art omics to characterize a novel function of the conserved regulatory protein, Ell2, in the lens. My research has made far-reaching impact by showning that proteins that have been historically considered as “general” regulators of transcription can specifically contribute to the regulation of a subset of key genes in tissue development, perturbation of which can result in developmental defects.University of Delaware, Department of Biological SciencesPh.D
Investigating daily associations between negative affect and impulsive urges among individuals with and without a lifetime history of self-directed and other-directed violence
No full textSadeh, NaomiObjectives: Impulsive urges and negative affect are transdiagnostic factors theorized to underlie risk for engagement in self- (SDV) and other-directed violence (ODV). Yet, the dynamic interplay between these factors at the within-person daily level remains poorly understood. Therefore, the present study aims to test within-person bidirectional associations between daily impulsive urges and negative affective states both within and between-days (Aim 1), and further evaluate the extent to which these daily associations are moderated by a history of engagement in SDV and ODV (Aim 2). ☐ Methods: A community sample of 84 adults (ages 18-55; 52.39% female) with and without histories of SDV and ODV participated in a 7-day daily diary survey during which they reported on their momentary impulsive urges and negative affective states in the morning and evenings. Hierarchical linear models were estimated to examine 1) within-person bidirectional associations between impulsive urges and negative affective states and 2) the moderating effect of SDV or ODV lifetime histories on these bidirectional associations. These relationships were examined across two-timescales: 1) within and 2) between days. ☐ Results: Impulsive urges and negative affective states were bidirectionally associated at the within-person level both within- and between- days (with the exception of negative affect on impulsive urges between-days). Further, we found SDV history moderated the within-person association between self-reported urges to act impulsively and next-day negative affectivity (β = 0.28, SE = 0.08, p = <0.001). An individual’s increase in impulsive urges, relative to their average levels, was associated with an increase in their negative affect the next day only for individuals with a history of SDV. In addition, ODV history moderated the within-person association between negative affective states and subsequent impulsive urges within-days (β = 0.26, SE = 0.11, p = 0.01). Specifically, an individual’s increase in negative affective states, relative to their average levels, was associated with increases in their impulsive urges within-days only for individuals with a history of ODV. ☐ Conclusion: Ultimately, findings from the present work reveal that, compared to those without a history of past violence perpetration, individuals with a history of SDV and ODV may experience amplified within-person associations between impulsive urges and negative affective states within- and between-days. These findings provide insight into the daily risk processes that may maintain vulnerability towards engagement in future violence in at-risk groups. A more thorough understanding of daily patterns of risk has the potential to inform violence prevention efforts targeting proximal risk factors, particularly among high-risk individuals. ☐ Keywords: Impulsivity, Negative Mood, Suicide, Aggression, Daily-DiaryUniversity of Delaware, Department of Psychological and Brain SciencesPh.D
The impact of white androgynous faces on binary gender categorization
No full textCloutier, JasminKubota, Jennifer T.Gender categorization is the use of visually derived semantic information to spontaneously sort individuals into socially established gender groups. Lack of gender-prototypicality disrupts the speed of binary gender categorization (Freeman et al., 2008) and gender non-conformity has been shown to lead to increased gender identity denial (Morgenroth et al., 2023). Limited research has used wholly gender-ambiguous stimuli, however, to examine the categorization of androgynous individuals. In this series of preregistered studies, we investigated the impact of androgyny on the binary gender categorization of faces. Participants categorized masculine, feminine, and androgynous white faces as men or women using a mouse-tracking design. Overall white androgynous faces produced significantly longer response times and less direct mouse trajectories compared to gender typical (masculine and feminine) faces. This indicates a higher level of competition between categories during the categorization of androgynous stimuli as a binary gender category compared to the categorization of gender typical stimuli. These results suggest androgyny acts as a disruptive force on spontaneous binary gender categorization. White androgynous faces were also significantly more likely to be categorized as woman than man, suggesting there are stricter expectations of prototypicality for the category of man compared to the category of woman.University of Delaware, Department of Psychological and Brain SciencesM.S
October, sexual politics, and the limits of postmodernism
No full text"At the request of the author or degree granting institution, this graduate work is not available to view or purchase until March 13 2026"-- ProQuest citation/abstract page.Gibson, Ann E.In a 1984 interview, the prominent critic and theorist, Craig Owens, characterized his writing in the October journal of the late 1970s and early 1980s as “a series of footnotes to Rosalind [Krauss’] writing... writing in the margins of her writing, her theoretical positions.” With this statement Owens gives an account of his paradoxical experience in postmodernism, his situation at once at the center and at the margins of that discourse. For as much as these words locate Owens’ position within Krauss’ intellectual circle, they also suggest the cost of his inclusion. In supporting Krauss’ theoretical positions in October, Owens was blind to his own queer encounters with postmodernism. ☐ This dissertation charts the limits of the October journal’s postmodernist discourse of art. It situates that discourse, which in its day became the dominant version of postmodernism, within the social history of the period of the journal’s greatest development, the late 1970s and early 1980s. That this social history (which includes the continued battles for women’s rights and civil rights, gay and lesbian liberation, as well as the simultaneous rise of the AIDS crisis and the new Christian Right) was for so long left out of October’s discussions of postmodernism and contemporary art in general is, I argue, a marker of the journal’s delimitation of the social to a mere generic point of reference. Thus, this dissertation is dedicated to an analysis of how and why October, despite its claims to the contrary, occluded representations of “the plural and multifarious character of contemporary social struggles” (in the words of Ernesto Laclau and Chantal Mouffe). In the face of contemporary art theory still beholden to October’s ostensibly progressive sensibilities, this dissertation argues that the journal’s postmodernism was in fact as resistant to the social politics of art as the modernism it claimed to supplant.University of Delaware, Department of Art HistoryPh.D
Magnon-induced electric polarization and magnon Nernst effects
No full textThis article was originally published in Proceedings of the National Academy of Sciences (PNAS). The version of record is available at: https://doi.org/10.1073/pnas.2507255122
Copyright © 2025 the Author(s). Published by PNAS. This article is distributed under Creative Commons Attribution-Non Commercial-No Derivatives License 4.0(CC BY-NC-ND). https://creativecommons.org/licenses/by-nc-nd/4.0/Magnons offer a promising path toward energy-efficient information transmission and the development of next-generation classical and quantum computing technologies. However, efficiently exciting, manipulating, and detecting magnons remains a critical need. We show that magnons, despite their charge-neutrality, can induce electric polarization through their spin and orbital moments. This effect is governed by system symmetry, magnon band hybridization, and interactions with other quasiparticles. We calculate the electric polarization induced by magnons in two-dimensional collinear honeycomb and noncollinear antiferromagnets (AFMs), showing that the presence of the Dzyaloshinskii-Moriya interaction yields a finite net electric polarization. In NiPSe3, a collinear honeycomb AFM with Zigzag order, the induced net electric polarization is about three orders of magnitude greater than in MnPS3, a collinear honeycomb AFM with Néel phase. In the noncollinear AFM KFe3(OH)6(SO4)2, the net electric polarization can be tuned via magnon hybridization, which can be controlled by external magnetic fields. These findings reveal that electric fields could be used to both detect and manipulate magnons under certain conditions by leveraging their spin and orbital angular moment. They also suggest that the discovery or engineering of materials with substantial magnon orbital moments could enhance practical uses of magnons for future computing and information transmission applications.DMR-2011824/National Science Foundation (NSF
Hydrodynamic lubrication at last: modulation of cartilage superlubricity by articulation speed, lubricant, and tissue properties
No full textPrice, ChristopherArticular cartilage is a phenomenal biological bearing material, easily sustaining friction coefficients (μ) 60mm/s, which promote interfacial hydrodynamics) and iii) in the presence of synovial fluid, have truly in vivo-like μ (<0.004) been demonstrated to be easily sustainable on the benchtop. ☐ Given the transformative advances in our understanding of biofidelic cartilage lubricity that have been enabled by the cSCA configuration, this dissertation aimed to precisely determine the mechanism(s) underlying cartilage superlubricity in the cSCA by establishing the relationship(s) between superlubricity (i.e., μ < 0.01) and sliding speed, lubricant choice and rheological behaviors, and cartilage mechanical properties. Thus, my objectives were: (1) to examine the influence of cartilage explant testing configuration and sliding speed on superlubricity outcomes; determine how SF presence promotes cartilage superlubricity (on the benchtop) via interrogation of the impact of (2) individual SF constituents and (3) non-SF-derived lubricants of shear-thinning behaviors and/or viscosities comparable to SF on cSCA lubrication, and (4) investigate whether, and how, cartilage mechanical properties alter these superlubricity behaviors. ☐ First, I established baseline sliding speed and testing configuration-dependent tribological behaviors with regards to the measured lubricity of articular cartilage explants—ex vivo (Aim 1 – Chapter 2). This work demonstrates that the selection of explant testing configuration and sliding speeds appears to be the strongest determinant of lubricant-dependent coefficients of friction in the tissue and validated that superlubricity on the benchtop is only supported by the rapid sliding of cSCA explants within a synovial fluid bath. Next, I interrogated the role of lubricant choice in mediating cartilage superlubricity outcomes by identifying, in isolation, the SF constituent—at physiological compositions—that replicates these behaviors, showing that hyaluronic acid is the sole constituent of SF necessary and sufficient for promoting/modulating superlubricity in the cSCA (Aim 1 – Chapter 3). Furthermore, I extended this interrogation of lubricant choice by leveraging non-physiological lubricant compositions—having comparable rheological behaviors to SF and hyaluronic acid-based fluids—to determine that lubricant viscosity, rather than presence of a specific macromolecular species, regulates superlubricity within the cSCA (Aim 2 – Chapter 4). Finally, I examined the influence of tissue mechanical properties and the ability of cartilage tissue to generate varying levels of fluid load support (titrated through tonicity) on the capacity of articular cartilage to support superlubricity, revealing that cartilage properties—across the range investigated—had minimal effect on cartilage ability to generate superlubricating behaviors on the benchtop, confirming the robustness of cSCA cartilage’s biofidelic lubrication behaviors (Aim 3 – Chapter 6). ☐ Collectively, these results comprehensively establish key/fundamental relationships among sliding speed, lubricant properties, and tissue mechanical properties that regulate/influence articular cartilage’s ability to approach and exceed the threshold for superlubricating operation on the benchtop, which we infer can be extended to the tissues in situ/in vivo operation. Furthermore, utilizing the expansive dataset collected that I collected for a Stribeck curve-based analysis of μ (Chapter 5), I have shown that articular cartilage lubrication broadly conforms to the well-established behaviors of classical engineered bearings. Such data indicates that despite its complex structure and (biphasic) composition, cartilage does not appear to be an inherently unique bearing material, as it functions nearly identically to that of classically understood engineered bearings when the tissue’s full operational environment is accounted for/explored. These findings will serve to transform the understanding of cartilage’s biofidelic lubricity and, for the first time, present direct evidence of full spectrum lubrication regimes that articular cartilage is capable of supporting/leveraging, including that of the oft debated and dismissed mechanism of hydrodynamic-mediated lubrication. This work, conducted nearly a century after the earliest experiments on cartilage lubrication, brings us full circle to the foundational theories of cartilage lubricity—and moves us significantly closer to finally answering the fundamental question of how cartilage truly works.University of Delaware, Department of Biomedical EngineeringPh.D