IU Indianapolis ScholarWorks :: Browsing by Author "Karnik, Sonali"

Browsing by Author "Karnik, Sonali"

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Anisotropic Properties of Articular Cartilage in an Accelerated In Vitro Wear Test
(Elsevier, 2020-09) Hossain, M. Jayed; Noori-Dokht, Hessam; Karnik, Sonali; Alyafei, Naomi; Joukar, Amin; Trippel, Stephen B.; Wagner, Diane R.; Mechanical and Energy Engineering, School of Engineering and Technology
Many material properties of articular cartilage are anisotropic, particularly in the superficial zone where collagen fibers have a preferential direction. However, the anisotropy of cartilage wear had not been previously investigated. The objective of this study was to evaluate the anisotropy of cartilage material behavior in an in vitro wear test. The wear and coefficient of friction of bovine condylar cartilage were measured with loading in directions parallel (longitudinal) and orthogonal (transverse) to the collagen fiber orientation at the articular surface. An accelerated cartilage wear test was performed against a T316 stainless-steel plate in a solution of phosphate buffered saline with protease inhibitors. A constant load of 160 N was maintained for 14000 cycles of reciprocal sliding motion at 4 mm/s velocity and a travel distance of 18 mm in each direction. The contact pressure during the wear test was approximately 2 MPa, which is in the range of that reported in the human knee and hip joint. Wear was measured by biochemically quantifying the glycosaminoglycans (GAGs) and collagen that was released from the tissue during the wear test. Collagen damage was evaluated with collagen hybridizing peptide (CHP), while visualization of the tissue composition after the wear test was provided with histologic analysis. Results demonstrated that wear in the transverse direction released about twice as many GAGs than in the longitudinal direction, but that no significant differences were seen in the amount of collagen released from the specimens. Specimens worn in the transverse direction had a higher intensity of CHP stain than those worn in the longitudinal direction, suggesting more collagen damage from wear in the transverse direction. No anisotropy in friction was detected at any point in the wear test. Histologic and CHP images demonstrate that the GAG loss and collagen damage extended through much of the depth of the cartilage tissue, particularly for wear in the transverse direction. These results highlight distinct differences between cartilage wear and the wear of traditional engineering materials, and suggest that further study on cartilage wear is warranted. A potential clinical implication of these results is that orienting osteochondral grafts such that the direction of wear is aligned with the primary fiber direction at the articular surface may optimize the life of the graft.
Correlation analysis of cartilage wear with biochemical composition, viscoelastic properties and friction
(Elsevier, 2023) Joukar, Amin; Creecy, Amy; Karnik, Sonali; Noori-Dokht, Hessam; Trippel, Stephen B.; Wallace, Joseph M.; Wagner, Diane R.; Orthopaedic Surgery, School of Medicine
Healthy articular cartilage exhibits remarkable resistance to wear, sustaining mechanical loads and relative motion for decades. However, tissues that replace or repair cartilage defects are much less long lasting. Better information on the compositional and material characteristics that contribute to the wear resistance of healthy cartilage could help guide strategies to replace and repair degenerated tissue. The main objective of this study was to assess the relationship between wear of healthy articular cartilage, its biochemical composition, and its viscoelastic material properties. The correlation of these factors with the coefficient of friction during the wear test was also evaluated. Viscoelastic properties of healthy bovine cartilage were determined via stress relaxation indentation. The same specimens underwent an accelerated, in vitro wear test, and the amount of glycosaminoglycans (GAGs) and collagen released during the wear test were considered measures of wear. The frictional response during the wear test was also recorded. The GAG, collagen and water content and the concentration of the enzymatic collagen crosslink pyridinoline were quantified in tissue that was adjacent to each wear test specimen. Finally, correlation analysis was performed to identify potential relationships between wear characteristics of healthy articular cartilage with its composition, viscoelastic material properties and friction. The findings suggest that stiffer cartilage with higher GAG, collagen and water content has a higher wear resistance. Enzymatic collagen crosslinks also enhance the wear resistance of the collagen network. The parameters of wear, composition, and mechanical stiffness of cartilage were all correlated with one another, suggesting that they are interrelated. However, friction was largely independent of these in this study. The results identify characteristics of healthy articular cartilage that contribute to its remarkable wear resistance. These data may be useful for guiding techniques to restore, regenerate, and stabilize cartilage tissue.
Creating Structured Hydrogel Microenvironments for Regulating Stem Cell Differentiation
(MDPI, 2020-12) Mills, David K.; Luo, Yangyang; Elumalai, Anusha; Esteve, Savannah; Karnik, Sonali; Yao, Shaomian; Mechanical and Energy Engineering, School of Engineering and Technology
The development of distinct biomimetic microenvironments for regulating stem cell behavior and bioengineering human tissues and disease models requires a solid understanding of cell–substrate interactions, adhesion, and its role in directing cell behavior, and other physico-chemical cues that drive cell behavior. In the past decade, innovative developments in chemistry, materials science, microfabrication, and associated technologies have given us the ability to manipulate the stem cell microenvironment with greater precision and, further, to monitor effector impacts on stem cells, both spatially and temporally. The influence of biomaterials and the 3D microenvironment’s physical and biochemical properties on mesenchymal stem cell proliferation, differentiation, and matrix production are the focus of this review chapter. Mechanisms and materials, principally hydrogel and hydrogel composites for bone and cartilage repair that create “cell-supportive” and “instructive” biomaterials, are emphasized. We begin by providing an overview of stem cells, their unique properties, and their challenges in regenerative medicine. An overview of current fabrication strategies for creating instructive substrates is then reviewed with a focused discussion of selected fabrication methods with an emphasis on bioprinting as a critical tool in creating novel stem cell-based biomaterials. We conclude with a critical assessment of the current state of the field and offer our view on the promises and potential pitfalls of the approaches discussed.
Decreased SIRT1 Activity Is Involved in the Acute Injury Response of Chondrocytes to Ex Vivo Injurious Mechanical Overload
(MDPI, 2023-03-30) Karnik, Sonali; Noori-Dokht, Hessam; Williams, Taylor; Joukar, Amin; Trippel, Stephen B.; Sankar, Uma; Wagner, Diane R; Mechanical and Energy Engineering, School of Engineering and Technology
A better understanding of molecular events following cartilage injury is required to develop treatments that prevent or delay the onset of trauma-induced osteoarthritis. In this study, alterations to SIRT1 activity in bovine articular cartilage explants were evaluated in the 24 h following a mechanical overload, and the effect of pharmacological SIRT1 activator SRT1720 on acute chondrocyte injury was assessed. SIRT1 enzymatic activity decreased as early as 5 min following the mechanical overload, and remained suppressed for at least 24 h. The chondrocyte injury response, including apoptosis, oxidative stress, secretion of inflammatory mediators, and alterations in cartilage matrix expression, was prevented with pharmacological activation of SIRT1 in a dose-dependent manner. Overall, the results implicate SIRT1 deactivation as a key molecular event in chondrocyte injury following a mechanical impact overload. As decreased SIRT1 signaling is associated with advanced age, these findings suggest that downregulated SIRT1 activity may be common to both age-related and injury-induced osteoarthritis.
Dysfunctional stem and progenitor cells impair fracture healing with age
(Baishideng Publishing Group, 2019-06-26) Wagner, Diane R.; Karnik, Sonali; Gunderson, Zachary J.; Nielsen, Jeffery J.; Fennimore, Alanna; Promer, Hunter J.; Lowery, Jonathan W.; Loghmani, M. Terry; Low, Philip S.; McKinley, Todd O.; Kacena, Melissa A.; Clauss, Matthias; Li, Jiliang; Orthopaedic Surgery, IU School of Medicine
Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.
Osteomacs promote maintenance of murine hematopoiesis through megakaryocyte-induced upregulation of Embigin and CD166
(Elsevier, 2024) Mohamad, Safa F.; El Koussa, Roy; Ghosh, Joydeep; Blosser, Rachel; Gunawan, Andrea; Layer, Justin; Zhang, Chi; Karnik, Sonali; Davé, Utpal; Kacena, Melissa A.; Srour, Edward F.; Microbiology and Immunology, School of Medicine
Maintenance of hematopoietic stem cell (HSC) function in the niche is an orchestrated event. Osteomacs (OM) are key cellular components of the niche. Previously, we documented that osteoblasts, OM, and megakaryocytes interact to promote hematopoiesis. Here, we further characterize OM and identify megakaryocyte-induced mediators that augment the role of OM in the niche. Single-cell mRNA-seq, mass spectrometry, and CyTOF examination of megakaryocyte-stimulated OM suggested that upregulation of CD166 and Embigin on OM augment their hematopoiesis maintenance function. CD166 knockout OM or shRNA-Embigin knockdown OM confirmed that the loss of these molecules significantly reduced the ability of OM to augment the osteoblast-mediated hematopoietic-enhancing activity. Recombinant CD166 and Embigin partially substituted for OM function, characterizing both proteins as critical mediators of OM hematopoietic function. Our data identify Embigin and CD166 as OM-regulated critical components of HSC function in the niche and potential participants in various in vitro manipulations of stem cells.
A Photochemical Crosslinking Approach to Enhance Resistance to Mechanical Wear and Biochemical Degradation of Articular Cartilage
(Sage, 2022) Noori-Dokht, Hessam; Joukar, Amin; Karnik, Sonali; Williams, Taylor; Trippel, Stephen B.; Wagner, Diane R.; Mechanical and Energy Engineering, School of Engineering and Technology
Objective: The objective of this study was to evaluate photochemical crosslinking using Al(III) phthalocyanine chloride tetrasulfonic acid (CASPc) and light with a wavelength of 670 nm as a potential therapy to strengthen articular cartilage and prevent tissue degradation. Design: Changes in viscoelastic properties with indentation were used to identify 2 crosslinking protocols for further testing. Crosslinked cartilage was subjected to an in vitro, accelerated wear test. The ability of the crosslinked tissue to resist biochemical degradation via collagenase was also measured. To better understand how photochemical crosslinking with CASPc varies through the depth of the tissue, the distribution of photo-initiator and penetration of light through the tissue depth was characterized. Finally, the effect of CASPc on chondrocyte viability and of co-treatment with an antioxidant was evaluated. Results: The equilibrium modulus was the most sensitive viscoelastic measure of crosslinking. Crosslinking decreased both mechanical wear and collagenase digestion compared with control cartilage. These beneficial effects were realized despite the fact that crosslinking appeared to be localized to a region near the articular surface. In addition, chondrocyte viability was maintained in crosslinked tissue treated with antioxidants. Conclusion: These results suggest that photochemical crosslinking with CASPc and 670 nm light holds promise as a potential therapy to prevent cartilage degeneration by protecting cartilage from mechanical wear and biochemical degradation. Limitations were also evident, however, as an antioxidant treatment was necessary to maintain chondrocyte viability in crosslinked tissue.
Repeated Mild Traumatic Brain Injury in Mice Elicits Long Term Innate Immune Cell Alterations in Blood, Spleen, and Brain
(Elsevier, 2023) Smith, Jared A.; Nguyen, Tyler; Karnik, Sonali; Davis, Brittany C.; Al-Juboori, Mohammed H.; Kacena, Melissa A.; Obukhov, Alexander G.; White, Fletcher A.; Anesthesia, School of Medicine
Mild traumatic brain injury is an insidious event whereby the initial injury leads to ongoing secondary neuro- and systemic inflammation through various cellular pathways lasting days to months after injury. Here, we investigated the impact of repeated mild traumatic brain injury (rmTBI) and the resultant systemic immune response in male C57B6 mice using flow cytometric methodology on white blood cells (WBCs) derived from the blood and spleen. Isolated mRNA derived from spleens and brains of rmTBI mice was assayed for changes in gene expression at one day, one week, and one month following the injury paradigm. We observed increases in Ly6C+, Ly6C-, and total monocyte percentages in both blood and spleen at one month after rmTBI. Differential gene expression analysis for the brain and spleen tissues uncovered significant changes in many genes, including csf1r, itgam, cd99, jak1,cd3ε, tnfaip6, and nfil3. Additional analysis revealed alterations in several immune signaling pathways over the course of one month in the brain and spleen of rmTBI mice. Together, these results indicate that rmTBI produces pronounced gene expression changes in the brain and spleen. Furthermore, our data suggest that monocyte populations may reprogram towards the proinflammatory phenotype over extended periods of time after rmTBI.
Therapeutic Applications of Halloysite
(MDPI, 2022) Mobaraki, Mohammadmahdi; Karnik, Sonali; Li, Yue; Mills, David K.; Orthopaedic Surgery, School of Medicine
In recent years, nanomaterials have attracted significant research interest for applications in biomedicine. Many kinds of engineered nanomaterials, such as lipid nanoparticles, polymeric nanoparticles, porous nanomaterials, silica, and clay nanoparticles, have been investigated for use in drug delivery systems, regenerative medicine, and scaffolds for tissue engineering. Some of the most attractive nanoparticles for biomedical applications are nanoclays. According to their mineralogical composition, approximately 30 different nanoclays exist, and the more commonly used clays are bentonite, halloysite, kaolinite, laponite, and montmorillonite. For millennia, clay minerals have been extensively investigated for use in antidiarrhea solutions, anti-inflammatory agents, blood purification, reducing infections, and healing of stomach ulcers. This widespread use is due to their high porosity, surface properties, large surface area, excellent biocompatibility, the potential for sustained drug release, thermal and chemical stability. We begin this review by discussing the major nanoclay types and their application in biomedicine, focusing on current research areas for halloysite in biomedicine. Finally, recent trends and future directions in HNT research for biomedical application are explored.

Browsing by Author "Karnik, Sonali"

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