Browsing by Author "Ravosa, Matthew J."

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    The fracture toughness of small animal cortical bone measured using arc-shaped tension specimens: Effects of bisphosphonate and deproteinization treatments
    (Elsevier, 2017-12) Hunckler, Michael D.; Chu, Ethan D.; Baumann, Andrew P.; Curtis, Tyler E.; Ravosa, Matthew J.; Allen, Matthew R.; Roeder, Ryan K.; Department of Anatomy and Cell Biology, School of Medicine
    Small animal models, and especially transgenic models, have become widespread in the study of bone mechanobiology and metabolic bone disease, but test methods for measuring fracture toughness on multiple replicates or at multiple locations within a single small animal bone are lacking. Therefore, the objective of this study was to develop a method to measure cortical bone fracture toughness in multiple specimens and locations along the diaphysis of small animal bones. Arc-shaped tension specimens were prepared from the mid-diaphysis of rabbit ulnae and loaded to failure to measure the radial fracture toughness in multiple replicates per bone. The test specimen dimensions, crack length, and maximum load met requirements for measuring the plane strain fracture toughness. Experimental groups included a control group, bisphosphonate treatment group, and an ex vivo deproteinization treatment following bisphosphonate treatment (5 rabbits/group and 15 specimens/group). The fracture toughness of ulnar cortical bone from rabbits treated with zoledronic acid for six months exhibited no difference compared with the control group. Partially deproteinized specimens exhibited significantly lower fracture toughness compared with both the control and bisphosphonate treatment groups. The deproteinization treatment increased tissue mineral density (TMD) and resulted in a negative linear correlation between the measured fracture toughness and TMD. Fracture toughness measurements were repeatable with a coefficient of variation of 12–16% within experimental groups. Retrospective power analysis of the control and deproteinization treatment groups indicated a minimum detectable difference of 0.1 MPa·m1/2. Therefore, the overall results of this study suggest that arc-shaped tension specimens offer an advantageous new method for measuring the fracture toughness in small animal bones.
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    Limitations of a morphological criterion of adaptive inference in the fossil record
    (Wiley, 2015) Ravosa, Matthew J.; Menegaz, Rachel A.; Scott, Jeremiah E.; Daegling, David J.; McAbee, Kevin R.; Department of Biomedical and Applied Sciences, IU School of Dentistry
    Experimental analyses directly inform how an anatomical feature or complex functions during an organism's lifetime, which serves to increase the efficacy of comparative studies of living and fossil taxa. In the mammalian skull, food material properties and feeding behaviour have a pronounced influence on the development of the masticatory apparatus. Diet-related variation in loading magnitude and frequency induce a cascade of changes at the gross, tissue, cellular, protein and genetic levels, with such modelling and remodelling maintaining the integrity of oral structures vis-à-vis routine masticatory stresses. Ongoing integrative research using rabbit and rat models of long-term masticatory plasticity offers unique insight into the limitations of functional interpretations of fossilised remains. Given the general restriction of the palaeontological record to bony elements, we argue that failure to account for the disparity in the hierarchical network of responses of hard versus soft tissues may overestimate the magnitude of the adaptive divergence that is inferred from phenotypic differences. Second, we note that the developmental onset and duration of a loading stimulus associated with a given feeding behaviour can impart large effects on patterns of intraspecific variation that can mirror differences observed among taxa. Indeed, plasticity data are relevant to understanding evolutionary transformations because rabbits raised on different diets exhibit levels of morphological disparity comparable to those found between closely related primate species that vary in diet. Lastly, pronounced variation in joint form, and even joint function, can also characterise adult conspecifics that differ solely in age. In sum, our analyses emphasise the importance of a multi-site and hierarchical approach to understanding determinants of morphological variation, one which incorporates critical data on performance.
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    Modeling the effect of ascites-induced compression on ovarian cancer multicellular aggregates
    (The Company of Biologists, 2018-09-25) Klymenko, Yuliya; Wates, Rebecca B.; Weiss-Bilka, Holly; Lombard, Rachel; Liu, Yueying; Campbell, Leigh; Kim, Oleg; Wagner, Diane; Ravosa, Matthew J.; Stack, M. Sharon; Mechanical and Energy Engineering, School of Engineering and Technology
    Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. EOC dissemination is predominantly via direct extension of cells and multicellular aggregates (MCAs) into the peritoneal cavity, which adhere to and induce retraction of peritoneal mesothelium and proliferate in the submesothelial matrix to generate metastatic lesions. Metastasis is facilitated by the accumulation of malignant ascites (500 ml to >2 l), resulting in physical discomfort and abdominal distension, and leading to poor prognosis. Although intraperitoneal fluid pressure is normally subatmospheric, an average intraperitoneal pressure of 30 cmH2O (22.1 mmHg) has been reported in women with EOC. In this study, to enable experimental evaluation of the impact of high intraperitoneal pressure on EOC progression, two new in vitro model systems were developed. Initial experiments evaluated EOC MCAs in pressure vessels connected to an Instron to apply short-term compressive force. A Flexcell Compression Plus system was then used to enable longer-term compression of MCAs in custom-designed hydrogel carriers. Results show changes in the expression of genes related to epithelial-mesenchymal transition as well as altered dispersal of compressed MCAs on collagen gels. These new model systems have utility for future analyses of compression-induced mechanotransduction and the resulting impact on cellular responses related to intraperitoneal metastatic dissemination.This article has an associated First Person interview with the first authors of the paper.
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    Ontogenetic and functional modularity in the rodent mandible
    (Elsevier, 2017) Menegaz, Rachel A.; Ravosa, Matthew J.; Department of Biomedical and Applied Sciences, IU School of Dentistry
    The material properties of diets consumed by juvenile individuals are known to affect adult morphological outcomes. However, much of the current experimental knowledge regarding dietary effects on masticatory form is derived from studies in which individuals are fed a non-variable diet for the duration of their postweaning growth period. Thus, it remains unclear how intra-individual variation in diet, due to ontogenetic variation in feeding behaviors or seasonal resource fluctuations, affects the resulting adult morphology. Furthermore, the mandible is composed of multiple developmental and functional subunits, and the extent to which growth and plasticity among these modules is correlated may be misestimated by studies that examine non-variable masticatory function in adults only. To address these gaps in our current knowledge, this study raised Sprague Dawley rats (n = 42) in four dietary cohorts from weaning to skeletal maturity. Two cohorts were fed a stable (“annual”) diet of either solid or powdered pellets. The other two cohorts were fed a variable (“seasonal”) diet consisting of solid/powdered pellets for the first half of the study, followed by a shift to the opposite diet. Results of longitudinal morphometric analyses indicate that variation in the mandibular corpus is more prominent at immature ontogenetic stages, likely due to processes of dental eruption and the growth of tooth roots. Furthermore, adult morphology is influenced by both masticatory function and the ontogenetic timing of this function, e.g., the consumption of a mechanically resistant diet. The morphology of the coronoid process was found to separate cohorts on the basis of their early weanling diet, suggesting that the coronoid process/temporalis muscle module may have an early plasticity window related to high growth rates during this life stage. Conversely, the morphology of the angular process was found to be influenced by the consumption of a mechanically resistant diet at any point during the growth period, but with a tendency to reflect the most recent diet. The prolonged plasticity window of the angular process/pterygomasseteric muscle module may be related to delayed ossification and muscular maturation within this module. The research presented here highlights the importance of more naturalistic models of mammalian feeding, and underscores the need for a better understanding of the processes of both morphological and behavioral maturation that follow weaning.