Browsing by Author "Matyas, John Robert"
Now showing 1 - 14 of 14
Results Per Page
Sort Options
- ItemOpen AccessThe Contribution of Endogenous and Exogenous Stem Cells in Fracture Repair(2019-12-17) Ferrie, Leah Elizabeth; Duncan, Neil A.; Krawetz, Roman J.; Matyas, John Robert; Rancourt, Derrick E.Throughout the lifespan, bone remodels in response to damage, such as fracture. However, diseases such as osteoporosis can cause impaired bone healing, increasing the risk of progression to non-repairing defects called fracture non-unions. Promoting the healing of fracture non-unions is a promising target for bone tissue engineering due to the limited success of current clinical treatment methods. There has been significant research on the use of stem cells with and without biomaterial scaffolds to treat bone fractures due to their promising regenerative capabilities. However, the relative roles of transplanted stem cells (exogenous stem cells) and stem cells found naturally in the body (endogenous stem cells) and their overall contribution to in vivo fracture repair is not well understood, thereby delaying the translation of new tissue engineering therapies to the clinic. The purpose of this research was to determine the interaction between exogenous and endogenous stem cells and biomaterials during bone fracture healing. This study was conducted using a burr-hole fracture model in a mesenchymal stem cell lineaging-tracing mouse. Burr-hole fractures were treated with collagen-I biomaterial loaded with and without green fluorescent protein tagged induced pluripotent stem cells. Using lineage-tracing, the roles of exogenous and endogenous stem cells during bone fracture repair could be elucidated. It was determined that in both a normal and impaired model of fracture healing treatment with exogenous stem cells did not result in improved bone formation and did not promote the recruitment of endogenous stem cells. However, treatment with exogenous stem cells in an impaired model of healing may offer healing advantages compared to in a normal model of healing. The outcomes of this study provide fundamental knowledge required for developing more effective stem cell and biomaterial therapies to treat bone fractures.
- ItemOpen AccessHigh-field MRI of articular cartilage: implications for the early diagnosis of osteoarthritis(2014-07-17) Mountain, Kelsey; Matyas, John RobertIn osteoarthritis (OA), a disabling and painful disease, articular cartilage is unable to perform its function of resisting loads and providing joint lubrication. The cause of OA remains unknown, as is the exact progression from early biochemical changes to the complete loss of cartilage. The extracellular matrix of articular cartilage is made up of a complex arrangement of water-imbibing glycosaminoglycans (GAG) that are held together by a tensioned network of collagen fibres. Some research evidence suggests that osteoarthritic changes commence at the articular surface, and are followed by a larger scale disruption of the extracellular matrix. An in vivo test of cartilage surface integrity could be an early and sensitive test for diagnosis and for monitoring the pathogenesis of OA. The objective of this thesis was to investigate the three-dimensional architecture of articular cartilage using novel imaging techniques and apply these techniques to a model of early osteoarthritis. Several key findings are presented. To better understand the collagen component in OA, tendon was studied on MRI, as it is relatively homogeneous. While studying the large scale influences of collagen orientation on the MRI parameter T2, it was revealed that MRI has sufficient resolving power to detect microscopic changes in collagen orientation (collagen crimp). Healthy articular cartilage was then used to develop specific imaging and microscopy techniques to assess and monitor the structure of the articular surface. Finally, T2 mapping and polarized light microscopy were applied to an animal model of early osteoarthritis, where they revealed notable changes in collagen organization at the articular surface in diseased samples. These studies contribute to the current understanding of articular cartilage structure in health and disease, and support the hypothesis that disruption of the articular surface is one of the initiating factors in osteoarthritis.
- ItemOpen AccessIdentifying indices of vulnerability in the aneurysmal abdominal aorta: The interplay between mechanics and morphology(2019-09-05) Ismaguilova, Alina; Di Martino, Elena S.; Matyas, John Robert; Tyberg, John V. T.; Edwards, William Brent; Natale, GiovanniantonioAn abdominal aortic aneurysm is the pathological dilatation of the abdominal aorta that can grow silently and rupture without warning. Over time, the vessel wall becomes weaker as inflammatory processes take over and the microarchitecture is compromised. Understanding the behaviour of the aneurysm wall at the macro and microscopic level can help elucidate the rupture potential of the vessel. This study proposes a novel method in assessing regions-specific differences by which we section the aorta into patches that can be traced back to specific areas on the aneurysm. The present study is thus an exploratory approach at assessing the aneurysms of multiple patients to establish differences between aneurysms, within aneurysms, and compare against healthy tissue. We established these differences, among others, using a variety of methods that assess the tissue microstructure, inflammation, composition, and mechanical response to loading. We also demonstrated the mechanical and structural heterogeneity in case studies exploring region-specific differences within the same patient. Coupling exploration into the pathophysiology of the aneurysm with its mechanical behaviour allowed us to paint a better picture of the disease, with mechanics often explaining biology and vice versa. We conclude that the pathological abdominal aorta exhibits a disruption in its extracellular matrix, profound inflammation, stiffer behaviour, and increased energy loss when compared with non-aneurysmal tissue. Ultimately, rupture risk assessment strategies need to utilize patient-specific parameters, and region-specific considerations need to be made.
- ItemOpen AccessIntercellular Gap Junction Communication in the Bovine Annulus Fibrosus(2019-02-21) McWhae, Russell; Duncan, Neil A.; Matyas, John Robert; Sen, Arindom; Li, Leping; Salo, Paul T.The intervertebral disc has a complex, anisotropic structure. The annulus fibrosus, the fibrous outer layer of the intervertebral disc, consists of fifteen to twenty-five concentric layers of collagen fibers at alternating orientations. Cells inside and between these lamellae are known to communicate with each other through gap junctions, protein channels that directly couple the membranes of adjacent cells and form interconnected networks that may be used to coordinate a response to mechanical stimuli. These fibroblastic cells fall into three distinct morphologies: spindle-shaped lamellar cells, round lamellar cells, and interlamellar cells. With confocal microscopy methods, gap-junctional intercellular signal propagation between groups of interconnected cells was examined. While the anisotropic microenvironment of the outer annulus was hypothesized to manifest in non-homogenous signal-propagation patterns, it was demonstrated that no clear directional biases or non-homogenous behavior existed among different cell morphologies and orientations; instead, intercellular signal propagation appears to be primarily proximity based.
- ItemOpen AccessMeasuring antler lengths using low-cost ToF cameras(2024-05-13) Cheng, Shu; Lichti, Derek; Matyas, John Robert; O'Keefe, Kyle; Bayat, Sayeh; Olsen, Michael J.Antlers have been widely used in pharmaceuticals, understanding regenerative mechanism, monitoring environmental pollutants as bio-indicators, and studying mechanical properties of bony tissues. Antler measurements play a significant role in these domains, indicating the antler growth stages, which are intricately linked to the medical properties, regenerative processes, and variations in pollutant levels within the antler. Traditionally, antler measurements are performed with contact methods like the measuring tape. The complex antler geometry entails multiple measurements and selection of reference points at various locations, making the process prone to human errors. The measuring process also requires manual capture or the use of drugs to keep the animal stationary, raising ethical and security concerns. To address these challenges and accurately monitor antler growth without causing any harm to the animals, an optical imaging method is proposed using a multi-camera system to obtain 3D antler data. The designed imaging system incorporates multiple Time-of-flight (ToF) cameras, an RGB camera, and an external trigger. The RGB camera detects animal motion, together with the external trigger, facilitates sequential data capture by the ToF cameras when animals are not moving substantially, thereby avoiding motion blur and camera interference. This mechanism ensures the collection of complete and usable antler data. In order to generate high quality antler data suitable for extracting measurements, a highly automated data processing workflow has been designed including antler quality control, segmentation, two-step registration and antler denoising. Animal motion and the low reflectivity of antlers are major factors degrading ToF camera data quality. To mitigate motion blur, animals are scanned during stationary periods and frames collected in each static period are merged as a weighted average for improved quality. The antler point cloud is automatically extracted by searching k-nearest neighbors from the environment data. The two-step registration involves registering multiple ToF cameras and aligning antler data from various static periods, which densify the antler data for manipulation. Ultimately, a polar coordinate-based denoising process filters out blunders and noise from the antler data for subsequent modelling process. An adaptive modelling approach has been developed to mathematically represent the antler data and facilitate measurement extraction. This method breaks down the 3D point cloud into slices and reconstructs the contour of each slice. The slice-based method strategically positions feature points where curvature changes occur, allowing for efficient storage and accurate reconstruction. Remarkably, this approach extends beyond antlers and can be applied to diverse shapes without prior knowledge. In summary, this research presents a comprehensive solution for monitoring antler growth, emphasizing precision, automation, and adaptability in the modeling processes and measurement extraction. This innovative approach not only advances antler related research but also lays the foundation for similar studies involving complex biological structures.
- ItemOpen AccessMicroglial Panx1 is a Spinal Determinant of Arthritis Joint Pain(2018-09-27) Mousseau, Michael James; Trang, Tuan; Matyas, John Robert; Altier, Christophe; Salo, Paul T.Pain is a debilitating feature of arthritis. Despite recent advances in treating joint inflammation and the widespread use of pain medications by arthritis patients, adequate pain control is an ongoing medical problem. A major challenge is that joint pain is poorly understood: some individuals with severe joint damage report little pain, whereas paradoxically others with seemingly minor joint damage complain of debilitating pain. This thesis examines how microglia in the spinal cord signal through pannexin-1 (Panx1) channels to mediate joint pain. My overarching hypothesis is that microglial Panx1 channels critically modulate arthritis joint pain and that silencing peripheral afferents suppresses microglial reactivity following joint injury. In rats, joint pain caused by intra-articular injection of monosodium iodoacetate (MIA) was associated with spinal adenosine triphosphate (ATP) release and an increase in spinal microglial reactivity. Here, I provide evidence that both C- and A-afferents modulate the development of mechanical allodynia in a model of MIA-induced joint pain. I also demonstrate that specific ablation of either peptidergic or non-peptidergic afferents can attenuate mechanical allodynia, decrease spinal microglial reactivity and suppress extracellular ATP concentration in the CSF of animals with MIA-induced joint damage. Following joint injury, I show a microglial-specific upregulation of P2X7-receptors (P2X7R). P2X7Rs drive pannexin-1 (Panx1) channel activation and, in rats with mechanical allodynia, Panx1 function is increased in spinal microglia. Specifically, I demonstrate that microglial Panx1-mediated release of the pro-inflammatory cytokine interleukin-1 (IL-1) induces mechanical allodynia in the MIA-injected hindlimb. Furthermore, I provide evidence that mice with a microglial-specific genetic deletion of Panx1 are protected from developing mechanical allodynia. Finally, I show that the clinically utilized broad-spectrum Panx1 blocker, probenecid, attenuates MIA-induced mechanical allodynia in two experimental models of arthritis and normalizes responses in the dynamic weight-bearing test, without impacting acute nociception. In conclusion, this thesis identifies that spinal microglial Panx1 channels are critically involved in the development of arthralgia and that Panx1-targeted therapy is a new mechanistic approach for alleviating joint pain.
- ItemOpen AccessMicroscale Mechanics and Structure of the Articular Cartilage Surface in Early Experimental Osteoarthritis(2013-01-25) Desrochers, Jane; Matyas, John RobertThe study of osteoarthritis (OA) – a painful and disabling disease characterized by disruption and loss of articular cartilage – is challenged by the fact that in most cases clinically recognizable signs and symptoms appear late in the osteoarthritic process, at which point structural and mechanical changes are already quite advanced. Consequently, the critical early events that occur when the disease process is potentially reversible are still not well defined. Although many of the exact details of the early natural history of OA are still unknown, clinical and experimental evidence suggest a degenerative progression beginning with disruption of the extracellular network at the articular surface. Since the articular surface cartilage has an important role in governing the mechanical behavior of the tissue, a better understanding of the early structural and mechanical changes of the cartilage surface that precede overt fibrillation and cartilage thinning would help to characterize the initiating pathogenic events in OA. The studies in this thesis support the presence of a discrete surface lamina and reveal distinct biochemical, structural and mechanical changes in this region in the early phases of experimental osteoarthritis. Micromechanical analyses reveal dramatic reductions in material properties of the articular surface in injured cartilage compared to contralateral controls including reductions in indentation moduli of up to six-fold; a decrease in the ratio of elastic vs. viscous material behavior; and an increase in surface friction coefficients under nanonewton-level applied normal forces. Changes in mechanical properties were associated with disintegration of the articular surface indicated by cracking and roughening of the cartilage surface and reduced fibrillar organization and thinning of the superficial zone. These analyses contribute to a better understanding of the depth- and scale-dependent properties of cartilage in health and disease. The mechanical data define a range of microscale structural and mechanical properties that can potentially be used as targets and inputs for: (1) repair tissues and tissue-engineered constructs for OA treatment; (2) clinical functional diagnostic tests of cartilage integrity; and (3) microscale and hierarchical computational models of cartilage force-deformation behavior.
- ItemOpen AccessThe Natural History of Bone Marrow Lesions and Cysts in the Dunkin-Hartley Guinea Pig Knee Osteoarthritis Model(2020-10-14) Francis, Destiny; Manske, Sarah Lynn; Matyas, John Robert; Dunn, Jeff F.Idiopathic knee osteoarthritis (OA) is a disease with unknown etiology, where age is described as a major risk factor. There is a need to document OA's natural history to gain insight into its etiology. Therefore, an animal model like the Dunkin-Hartley (DH) guinea pig that spontaneously develops a knee OA phenotype similar to idiopathic OA observed in humans can be used to study the disease-related bony degeneration. This phenotype includes osteophyte formation, sclerosis, bone marrow lesions (BMLs), and cysts within a relatively short period. This thesis employs advanced magnetic resonance imaging (MRI), micro-computed tomography (μCT), and histological techniques to assess knee joint degeneration in DH guinea pigs at ages 2, 4, 6, 12, and 24 months. The results from this project show evidence of cartilage degradation and bone cyst formation in the 6-month age group, which becomes more apparent in the 12 and 24-month age groups. When present, cysts were primarily located in the central compartment of the bone and often accompanied by osteophytes and sclerosis. Joint degeneration was most severe in the 24-month age group with the largest cysts as well as the greatest osteophyte size and number. Bone microarchitecture was also significantly affected in this age group. Overall femoral and tibial trabecular number (Tb.N) was lowest in the 24-month age group, and it had the highest medial femoral subchondral bone plate thickness (Sbp.Th), femoral and tibial subchondral bone plate porosity (Sbp.Po), femoral trabecular separation (Tb.Sp), and medial tibial trabecular thickness (Tb.Th). The medial compartment also revealed greater joint degeneration, as demonstrated by greater femoral and tibial Sbp.Th and femoral Sbp.Po in the 12 and 24-month age groups compared with the lateral compartment. This project demonstrates that age-related joint degeneration occurs in the DH guinea pig spontaneous knee OA model with evidence of osteophytes, cysts, and bone microarchitecture alterations in older age groups. Although histology revealed abnormalities in the bone that have been associated with MRI-defined BMLs, I am unable to conclude whether or not BMLs occur in this model as a further investigation with MRI is still required.
- ItemOpen AccessThe progression of bone microarchitecture changes following an acute knee injury in young adults(2019-03-18) Kroker, Andres Mauricio; Boyd, Steven Kyle; Walker, Richard E. A.; Matyas, John Robert; Manske, Sarah Lynn; Van-Rietbergen, Bert; Doyle-Baker, Patricia K.Anterior cruciate ligament (ACL) tears are activity-related knee injuries associated with an elevated risk of developing post-traumatic osteoarthritis 10-20 years post-injury. Immediately after the injury bone mass is lost. This is followed by a recovery period, though full recovery is not achieved even years later. Due to a lack of appropriate imaging modalities, no information is available on how the underlying bone microarchitecture is affected. In addition, the effects of concurrent soft-tissue injuries, such as meniscus tears or traumatic bone marrow lesions, on the underlying bone microarchitecture in human knees are not known. In this thesis, a new method for in vivo assessment of bone microarchitecture of the human knee is introduced. Next, in two cross-sectional studies this technique is applied to populations that experienced unilateral ACL tears six to nine years earlier. Both studies revealed that bone is primarily affected in the femur of the injured knee. Trabecular bone mass is lower in the medial femur (-4.8% to -10.4%) while the subchondral bone plate is thicker in the lateral femur (9% to 29.6%) as compared to the contralateral knee. Further, the thicker subchondral bone plate is associated with surgical meniscus treatment (meniscectomy or repair) at the time of ligament reconstruction. In a year-long longitudinal study, the new imaging technique is applied to a cohort with acute unilateral ACL tears to investigate how early injury-induced bone changes affect microstructure. Immediately following the injury, trabecular bone is lost throughout the injured knee (-4.9% to -15.8%), driven by a loss of trabecular elements and increased trabecular separation. Concurrently, the subchondral bone plate of the lateral femur thins (-9%). The trabecular bone changes are further accelerated in traumatic bone marrow lesions (-18.2% to -20.6%). These findings show that while initial bone mass loss following the injury may recover six to nine years later (primarily in the tibia), the femur is affected long-term. The underlying structural changes are believed to be permanent, and while it is not known which individuals will develop osteoarthritis, limiting early injury-induced bone changes may reduce long-term risk of joint degradation.
- ItemOpen AccessProteoglycan-4 in Equine Joint Disease, Exercise, and in vitro Cartilage Repair(2020-05-25) Matheson, Austyn Reid; Schmidt, Tannin A.; Scott, W. Michael; Herzog, Walter; Matyas, John RobertProteoglycan-4 (PRG4) and hyaluronan (HA) are biological macromolecules with varied and diverse functions distributed throughout the body. In synovial fluid (SF), PRG4 and HA provide independent and synergistic contributions to tissue health and cartilage boundary lubrication. The biological consequences of joint injury or disease such as osteoarthritis (OA) may include altered concentration, structure, and function of PRG4 and HA, leading to degraded SF quality and function, changes which are not fully understood. Furthermore, the effects of joint disease on circulating (serum) PRG4 and HA, both of unknown origin and function in blood, requires clarification. Monitoring changes to PRG4 and HA to elucidate the effects on SF and serum may facilitate the development of therapeutics, biomarkers, or novel biomaterials to restore joint health and function. The objectives of this thesis were to 1) investigate clinically relevant changes to PRG4 and HA composition in SF and serum, and SF biomechanical function from equine cases of joint disease and injury, 2) to investigate the effect of exercise on equine serum PRG4, and 3) to characterize the effect of recombinant human PRG4 (rhPRG4) integration on the biomechanical, architectural, and biological aspects of a collagen-based scaffold for cartilage repair. A combination of novel and previously characterized biochemical and biomechanical techniques were used to evaluate SF and serum composition, the lubricating ability of SF and tissue-engineered collagen-scaffolds, and the in vitro bioactivity of rhPRG4-integrated collagen-scaffolds. The composition of equine SF changed in acute joint injury compared to SF from normal horses. Both PRG4 concentration and HA molecular weight were altered, with decreased SF viscosity, yet no associated detectable effects on serum PRG4. The concentration of serum PRG4 in a group of racehorses decreased significantly five minutes post-exercise, perhaps clearing from the circulation. Hence, serum PRG4 and HA concentrations alone may not be useful biomarkers for equine joint disease. rhPRG4-integrated scaffolds had enhanced lubricating properties, a highly porous architecture, and supported cell infiltration and growth across most concentrations tested. Collectively these results indicate that PRG4 is an essential lubricant, an indicator for injury, and a promising therapeutic for integration within cartilage repair biomaterials.
- ItemOpen AccessStudies of Structural and Mechanical Properties of Skin and Treated Split Thickness Skin Autografts(2018-09-06) Tarraf, Samar Andrea; Di Martino, Elena S.; Biernaskie, Jeff A.; Duncan, Neil A.; Matyas, John RobertSplit-thickness skin autografts (STSGs) are the gold standard treatment for full thickness burn wounds. Healthy skin from the patient is harvested and transplanted onto the wound. The graft, comprised of epidermis and superficial dermis, is missing cellular components adversely affecting functionality. One major contributor to reduced functionality is decreased elasticity. Understanding the biomechanical properties of grafts can help assess the efficacy of treatments. We hypothesize that combining STSGs with dermal stem cells could stimulate tissue remodeling, generation of neodermis and improve functionality. Coupling mechanics with microscopy assays gives a more encompassing understanding of the changes in mechanical properties. This study provides an initial comparison between skin tissue types and between graft treatments. We established differences between healthy and grafted skin and showed shortcomings of the xenograft model used. We also demonstrated the effects of graft treatment on mechanical response. Treatment cannot fully recover healthy skin behavior, but improves graft functionality.
- ItemOpen AccessThe Structure and function of the insertions of the rabbit medial collateral ligament : an experim(1990) Matyas, John Robert; Frank, Cyril B.
- ItemOpen Access
- ItemOpen AccessTranslamellar Cross-Bridge Structures of the Intervertebral Disc(2020-01-21) Urbinsky, Chris; Duncan, Neil A.; Dunn, Jeff F.; Matyas, John RobertThe annulus fibrosus of the intervertebral disc is comprised of layers of circumferential lamellae. Previous studies have also identified radial structures dubbed translamellar cross-bridges, but the full extent, concentration, interconnection and their mechanical contribution, are poorly understood. The objectives of this study were to use a combination of magnetic resonance imaging (MRI) and optical coherence tomography (OCT) to document the cross-bridges in 3D and to measure the strength and stiffness of the cross-bridges using a peel test between lamellae. The images produced show an interconnected network of bridge structures throughout the annulus. The mechanical contribution proved difficult to separate from the remaining interlamellar matrix contribution, but comparing load curves between sample thicknesses, and with OCT images of the samples, did suggest discrete, radial structures influence the peel strength. This study will contribute to future tissue engineering efforts by increasing the current understanding of the native disc structure.