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Kyriacos A. Athanasiou - One of the best experts on this subject based on the ideXlab platform.

  • Considerations for translation of tissue engineered fibrocartilage from bench to bedside.
    Journal of Biomechanical Engineering, 2019
    Co-Authors: Ryan P. Donahue, Erik A. Gonzalez-leon, Kyriacos A. Athanasiou
    Abstract:

    Fibrocartilage is found in the Knee Meniscus, the temporomandibular joint (TMJ) disc, the pubic symphysis, the annulus fibrosus of intervertebral disc, tendons, and ligaments. These tissues are notoriously difficult to repair due to their avascularity, and limited clinical repair and replacement options exist. Tissue engineering has been proposed as a route to repair and replace fibrocartilages. Using the Knee Meniscus and TMJ disc as examples, this review describes how fibrocartilages can be engineered toward translation to clinical use. Presented are fibrocartilage anatomy, function, epidemiology, pathology, and current clinical treatments because they inform design criteria for tissue engineered fibrocartilages. Methods for how native tissues are characterized histomorphologically, biochemically, and mechanically to set gold standards are described. Then, provided is a review of fibrocartilage-specific tissue engineering strategies, including the selection of cell sources, scaffold or scaffold-free methods, and biochemical and mechanical stimuli. In closing, the Food and Drug Administration paradigm is discussed to inform researchers of both the guidance that exists and the questions that remain to be answered with regard to bringing a tissue engineered fibrocartilage product to the clinic.

  • Tendon and ligament as novel cell sources for engineering the Knee Meniscus.
    Osteoarthritis and cartilage, 2016
    Co-Authors: Pasha Hadidi, Nikolaos K. Paschos, Brian J. Huang, Ashkan Aryaei, Kyriacos A. Athanasiou
    Abstract:

    Summary Objective The application of cell-based therapies in regenerative medicine is hindered by the difficulty of acquiring adequate numbers of competent cells. For the Knee Meniscus in particular, this may be solved by harvesting tissue from neighboring tendons and ligaments. In this study, we have investigated the potential of cells from tendon and ligament, as compared to Meniscus cells, to engineer scaffold-free self-assembling fibrocartilage. Method Self-assembling Meniscus-shaped constructs engineered from a co-culture of articular chondrocytes and either Meniscus, tendon, or ligament cells were cultured for 4 weeks with TGF-β1 in serum-free media. After culture, constructs were assessed for their mechanical properties, histological staining, gross appearance, and biochemical composition including cross-link content. Correlations were performed to evaluate relationships between biochemical content and mechanical properties. Results In terms of mechanical properties as well as biochemical content, constructs engineered using tenocytes and ligament fibrocytes were found to be equivalent or superior to constructs engineered using Meniscus cells. Furthermore, cross-link content was found to be correlated with engineered tissue tensile properties. Conclusion Tenocytes and ligament fibrocytes represent viable cell sources for engineering Meniscus fibrocartilage using the self-assembling process. Due to greater cross-link content, fibrocartilage engineered with tenocytes and ligament fibrocytes may maintain greater tensile properties than fibrocartilage engineered with Meniscus cells.

  • Building an Anisotropic Meniscus with Zonal Variations
    Tissue engineering. Part A, 2013
    Co-Authors: Michael M. Higashioka, Justin A. Chen, Kyriacos A. Athanasiou
    Abstract:

    Toward addressing the difficult problems of Knee Meniscus regeneration, a self-assembling process has been used to re-create the native morphology and matrix properties. A significant problem in such attempts is the recapitulation of the distinct zones of the Meniscus, the inner, more cartilaginous and the outer, more fibrocartilaginous zones. In this study, an anisotropic and zonally variant Meniscus was produced by self-assembly of the inner Meniscus (100% chondrocytes) followed by cell seeding the outer Meniscus (coculture of chondrocytes and Meniscus cells). After 4 weeks in culture, the engineered, inner Meniscus exhibited a 42% increase in both instantaneous and relaxation moduli and a 62% increase in GAG/DW, as compared to the outer Meniscus. In contrast, the circumferential tensile modulus and collagen/DW of the outer zone was 101% and 129% higher, respectively, than the values measured for the inner zone. Furthermore, there was no difference in the radial tensile modulus between the control and zonal engineered menisci, suggesting that the inner and outer zones of the engineered zonal menisci successfully integrated. These data demonstrate that not only can biomechanical and biochemical properties be engineered to differ by the zone, but they can also recapitulate the anisotropic behavior of the Knee Meniscus.

  • Biomechanics of Meniscus Cells: Regional Variation and Comparison to Articular Chondrocytes and Ligament Cells
    Biomechanics and modeling in mechanobiology, 2012
    Co-Authors: Johannah Sanchez-adams, Kyriacos A. Athanasiou
    Abstract:

    Central to understanding mechanotransduction in the Knee Meniscus is the characterization of Meniscus cell mechanics. In addition to biochemical and geometric differences, the inner and outer regions of the Meniscus contain cells that are distinct in morphology and phenotype. This study investigated the regional variation in Meniscus cell mechanics in comparison with articular chondrocytes and ligament cells. It was found that the Meniscus contains two biomechanically distinct cell populations, with outer Meniscus cells being stiffer (1.59 ± 0.19 kPa) than inner Meniscus cells (1.07 ± 0.14 kPa). Additionally, it was found that both outer and inner Meniscus cell stiffnesses were similar to ligament cells (1.32 ± 0.20 kPa), and articular chondrocytes showed the highest stiffness overall (2.51 ± 0.20 kPa). Comparison of compressibility characteristics of the cells showed similarities between articular chondrocytes and inner Meniscus cells, as well as between outer Meniscus cells and ligament cells. These results show that cellular biomechanics vary regionally in the Knee Meniscus and that Meniscus cells are biomechanically similar to ligament cells. The mechanical properties of musculoskeletal cells determined in this study may be useful for the development of mathematical models or the design of experiments studying mechanotransduction in a variety of soft tissues.

  • Regional effects of enzymatic digestion on Knee Meniscus cell yield and phenotype for tissue engineering.
    Tissue engineering. Part C Methods, 2011
    Co-Authors: Johannah Sanchez-adams, Kyriacos A. Athanasiou
    Abstract:

    An abundant cell source is the cornerstone of most tissue engineering strategies, but extracting cells from the Knee Meniscus is hindered by its dense fibrocartilaginous matrix. Identifying a method to efficiently isolate Meniscus cells is important, as it can reduce the cost and effort required to perform Meniscus engineering research. In this study, six enzymatic digestion regimens used for cartilaginous cell isolation were used to isolate cells from the outer, middle, and inner regions of the bovine Knee Meniscus. Each regimen in each region was assessed in terms of cell yield, impact on cell phenotype, and cytotoxicity. All digestion regimens caused an overall upregulation of cartilage-specific genes Sox9, collagen type I (Col 1), collagen type II (Col 2), cartilage oligomeric matrix protein, and aggrecan (AGC) in cells from all Meniscus regions, but was highest for cells isolated using 1075 U/mL of collagenase for 3 h (high collagenase). In response to isolation, outer Meniscus cells showed highest u...

Dawn M. Elliott - One of the best experts on this subject based on the ideXlab platform.

  • Short cracks in Knee Meniscus tissue cause strain concentrations, but do not reduce ultimate stress, in single-cycle uniaxial tension.
    Royal Society open science, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local...

  • short cracks in Knee Meniscus tissue cause strain concentrations but do not reduce ultimate stress in single cycle uniaxial tension
    Royal Society Open Science, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local rupture and reduce effective strength. It is currently unknown if cracks in Meniscus have these consequences; if they do, this would have repercussions for management of Meniscus pathology. The objective of this study was to determine if a short crack in Meniscus tissue, which mimics a preclinical Meniscus tear, (a) causes crack growth and reduces effective strength, (b) creates a near-tip strain concentration and (c) creates unloaded regions on either side of the crack. Specimens with and without cracks were tested in uniaxial tension and compared in terms of macroscopic stress-strain curves and digital image correlation strain fields. The strain fields were used as an indicator of stress concentrations and unloaded regions. Effective strength was found to be insensitive to the presence of a crack (potential effect < 0.86 s.d.; β = 0.2), but significant strain concentrations, which have the potential to lead to long-term accumulation of tissue or cell damage, were observed near the crack tip.

  • short cracks in Knee Meniscus tissue cause strain concentrations but do not reduce ultimate stress in single cycle uniaxial tension
    bioRxiv, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local rupture and reduce effective strength. It is currently unknown if cracks in Meniscus have these consequences; if they do, this would have repercussions for management of Meniscus pathology. The objective of this study was to determine if a short crack in Meniscus tissue, which mimics a preclinical Meniscus tear, (a) causes crack growth and reduces effective strength, (b) creates a near-tip strain concentration, and (c) creates unloaded regions on either side of the crack. Specimens with and without cracks were tested in uniaxial tension and compared in terms of macroscopic stress-strain curves and digital image correlation strain fields. The strain fields were used as an indicator of stress concentrations and unloaded regions. Effective strength was found to be insensitive to the presence of a crack (potential effect

  • Short cracks in Knee Meniscus tissue cause strain concentrations, but not weakness, in single-cycle uniaxial tension
    2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology. From a mechanical perspective, Meniscus tears are a type of crack-like defect. In many materials, cracks create stress concentrations that cause failure by fracture and thereby reduce the material9s effective strength. It is currently unknown whether the Meniscus is vulnerable to fracture. If Meniscus tears cause fracture, this would have significant repercussions for management of Meniscus pathology. The objective of this study was to determine if short crack-like defects in the Meniscus, representing short Meniscus tears, cause fracture and, by unloading the cut region, stress concentrations. Failure stress was compared between cracked and control specimens to determine if fracture occurred. Strain concentrations near the crack tip were quantified using digital image correlation (DIC) and used as an indicator of stress concentrations. The presence of cracks did not affect the Meniscus9 failure stress (effect

  • MULTI-LAMELLAR AND MULTI-AXIAL MATURATION OF CELL-SEEDED FIBER- REINFORCED TISSUE ENGINEERED CONSTRUCTS
    ASME 2007 Summer Bioengineering Conference, 2007
    Co-Authors: Brendon M. Baker, Dawn M. Elliott, Grace D. O'connell, Sounok Sen, Ashwin S. Nathan, Robert L. Mauck
    Abstract:

    The architecture of load-bearing fibrous tissues is optimized to enable a specific set of mechanical functions. This organization arises from a complex process of cell patterning, matrix deposition, and functional maturation [1]. In their mature state, these tissues span multiple length scales, encompassing nanoscale interactions of cells with extracellular matrix to the centimeter length scales of the anatomic tissue volume and shape. Two structures that typify dense fibrous tissues are the Meniscus of the Knee and the annulus fibrosus (AF) of the intervertebral disc (IVD). The mechanical function of the wedge-shaped Knee Meniscus is based on its stiff prevailing circumferential collagen architecture that resists tensile deformation [2,3]. Adding to its complexity, radial tie fibers and sheets are interwoven amongst these fibers, increasing stiffness in the transverse direction and binding the tissue together [4]. In the annulus fibrosus, multiple anisotropic lamellae are stacked in concentric rings with their prevailing fiber directions alternating above and below the horizontal axis in adjacent layers [5]. The high circumferential tensile properties of this laminate structure allow it to resist bulging of the nucleus pulposus with compressive loading of the spine. Given their structural properties, unique form, and demanding mechanical environments, the Knee Meniscus and the AF region of the IVD represent two of the most challenging tissues to consider for functional tissue engineering.Copyright © 2007 by ASME

James E. Kennedy - One of the best experts on this subject based on the ideXlab platform.

  • An evaluation of the biocompatibility properties of a salt-modified polyvinyl alcohol hydrogel for a Knee Meniscus application.
    Materials science & engineering. C Materials for biological applications, 2015
    Co-Authors: Jennifer C. Hayes, James E. Kennedy
    Abstract:

    The treatment of irreparable Knee Meniscus tears remains a major challenge for the orthopaedic community. The main purpose of this research was to analyse the biocompatibility properties of a salt-modified polyvinyl alcohol hydrogel, in order to assess its potential for use as an artificial meniscal implant. Aqueous polyvinyl alcohol was treated with a sodium sulphate solution to precipitate out the polyvinyl alcohol resulting in a pliable hydrogel. Cytotoxicological analysis indicates that PVA/sodium sulphate hydrogels display a non-toxic disposition and were found to be compatible with the L929 fibroblast cell line.

  • An evaluation of the thermal and mechanical properties of a salt-modified polyvinyl alcohol hydrogel for a Knee Meniscus application
    Journal of the mechanical behavior of biomedical materials, 2014
    Co-Authors: Colin Curley, Jennifer C. Hayes, Neil J. Rowan, James E. Kennedy
    Abstract:

    The treatment of irreparable Knee Meniscus tears remains a major challenge for the orthopaedic community. The main purpose of this research was to analyse the mechanical properties and thermal behaviour of a salt-modified polyvinyl alcohol hydrogel, in order to assess its potential for use as an artificial meniscal implant. Aqueous poly vinyl alcohol was treated with a sodium sulphate solution to precipitate out the polyvinyl alcohol resulting in a pliable hydrogel. The freeze-thaw process, a strictly physical method of crosslinking, was employed to crosslink the hydrogel. Physical crosslinks in the form of crystalline regions were induced within the hydrogel structure which resulted in a large increase in mechanical resistance. Results showed that the optimal sodium sulphate addition of 6.6% (w/v) Na2SO4 in 8.33% (w/v) PVA causes the PVA to precipitate out of its solution. The effect of multiple freeze thaw cycles was also investigated. Investigation comprised of a variety of well-established characterisation techniques such as differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), mechanical analysis, rheometry and swelling studies. DSC analysis showed that samples cross-linked using the freeze thaw process display a thermal shift due to increased crosslink density. FTIR analysis confirmed crystallisation is present at 1142cm(-1) and also showed that no chemical alteration occurs when PVA is treated with sodium sulphate. Swelling studies indicated that that PVA/sodium sulphate hydrogels absorb less water than untreated hydrogels due to increased amounts of PVA present. Compressive strength analysis of PVA/sodium sulphate hydrogels prepared at -80°C displayed average maximum loads of 2472N, 2482.4N and 2476N of over 1, 3 and 5 freeze thaw cycles respectively. Mechanical analysis of the hydrogel indicated that the material is thermally stable and resistant to breakdown by compressive force. These properties are crucial for potential use as a Meniscus or cartilage replacement. As such, the results of this study indicate that polyvinyl alcohol modified with sodium sulphate may be a suitable material for the construction of an artificial Knee Meniscus.

John M. Peloquin - One of the best experts on this subject based on the ideXlab platform.

  • Short cracks in Knee Meniscus tissue cause strain concentrations, but do not reduce ultimate stress, in single-cycle uniaxial tension.
    Royal Society open science, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local...

  • short cracks in Knee Meniscus tissue cause strain concentrations but do not reduce ultimate stress in single cycle uniaxial tension
    Royal Society Open Science, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local rupture and reduce effective strength. It is currently unknown if cracks in Meniscus have these consequences; if they do, this would have repercussions for management of Meniscus pathology. The objective of this study was to determine if a short crack in Meniscus tissue, which mimics a preclinical Meniscus tear, (a) causes crack growth and reduces effective strength, (b) creates a near-tip strain concentration and (c) creates unloaded regions on either side of the crack. Specimens with and without cracks were tested in uniaxial tension and compared in terms of macroscopic stress-strain curves and digital image correlation strain fields. The strain fields were used as an indicator of stress concentrations and unloaded regions. Effective strength was found to be insensitive to the presence of a crack (potential effect < 0.86 s.d.; β = 0.2), but significant strain concentrations, which have the potential to lead to long-term accumulation of tissue or cell damage, were observed near the crack tip.

  • short cracks in Knee Meniscus tissue cause strain concentrations but do not reduce ultimate stress in single cycle uniaxial tension
    bioRxiv, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local rupture and reduce effective strength. It is currently unknown if cracks in Meniscus have these consequences; if they do, this would have repercussions for management of Meniscus pathology. The objective of this study was to determine if a short crack in Meniscus tissue, which mimics a preclinical Meniscus tear, (a) causes crack growth and reduces effective strength, (b) creates a near-tip strain concentration, and (c) creates unloaded regions on either side of the crack. Specimens with and without cracks were tested in uniaxial tension and compared in terms of macroscopic stress-strain curves and digital image correlation strain fields. The strain fields were used as an indicator of stress concentrations and unloaded regions. Effective strength was found to be insensitive to the presence of a crack (potential effect

  • Short cracks in Knee Meniscus tissue cause strain concentrations, but not weakness, in single-cycle uniaxial tension
    2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology. From a mechanical perspective, Meniscus tears are a type of crack-like defect. In many materials, cracks create stress concentrations that cause failure by fracture and thereby reduce the material9s effective strength. It is currently unknown whether the Meniscus is vulnerable to fracture. If Meniscus tears cause fracture, this would have significant repercussions for management of Meniscus pathology. The objective of this study was to determine if short crack-like defects in the Meniscus, representing short Meniscus tears, cause fracture and, by unloading the cut region, stress concentrations. Failure stress was compared between cracked and control specimens to determine if fracture occurred. Strain concentrations near the crack tip were quantified using digital image correlation (DIC) and used as an indicator of stress concentrations. The presence of cracks did not affect the Meniscus9 failure stress (effect

Michael H. Santare - One of the best experts on this subject based on the ideXlab platform.

  • Short cracks in Knee Meniscus tissue cause strain concentrations, but do not reduce ultimate stress, in single-cycle uniaxial tension.
    Royal Society open science, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local...

  • short cracks in Knee Meniscus tissue cause strain concentrations but do not reduce ultimate stress in single cycle uniaxial tension
    Royal Society Open Science, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local rupture and reduce effective strength. It is currently unknown if cracks in Meniscus have these consequences; if they do, this would have repercussions for management of Meniscus pathology. The objective of this study was to determine if a short crack in Meniscus tissue, which mimics a preclinical Meniscus tear, (a) causes crack growth and reduces effective strength, (b) creates a near-tip strain concentration and (c) creates unloaded regions on either side of the crack. Specimens with and without cracks were tested in uniaxial tension and compared in terms of macroscopic stress-strain curves and digital image correlation strain fields. The strain fields were used as an indicator of stress concentrations and unloaded regions. Effective strength was found to be insensitive to the presence of a crack (potential effect < 0.86 s.d.; β = 0.2), but significant strain concentrations, which have the potential to lead to long-term accumulation of tissue or cell damage, were observed near the crack tip.

  • short cracks in Knee Meniscus tissue cause strain concentrations but do not reduce ultimate stress in single cycle uniaxial tension
    bioRxiv, 2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology and, from a mechanical perspective, are crack-like defects (cracks). In many materials, cracks create stress concentrations that cause progressive local rupture and reduce effective strength. It is currently unknown if cracks in Meniscus have these consequences; if they do, this would have repercussions for management of Meniscus pathology. The objective of this study was to determine if a short crack in Meniscus tissue, which mimics a preclinical Meniscus tear, (a) causes crack growth and reduces effective strength, (b) creates a near-tip strain concentration, and (c) creates unloaded regions on either side of the crack. Specimens with and without cracks were tested in uniaxial tension and compared in terms of macroscopic stress-strain curves and digital image correlation strain fields. The strain fields were used as an indicator of stress concentrations and unloaded regions. Effective strength was found to be insensitive to the presence of a crack (potential effect

  • Short cracks in Knee Meniscus tissue cause strain concentrations, but not weakness, in single-cycle uniaxial tension
    2018
    Co-Authors: John M. Peloquin, Michael H. Santare, Dawn M. Elliott
    Abstract:

    Tears are central to Knee Meniscus pathology. From a mechanical perspective, Meniscus tears are a type of crack-like defect. In many materials, cracks create stress concentrations that cause failure by fracture and thereby reduce the material9s effective strength. It is currently unknown whether the Meniscus is vulnerable to fracture. If Meniscus tears cause fracture, this would have significant repercussions for management of Meniscus pathology. The objective of this study was to determine if short crack-like defects in the Meniscus, representing short Meniscus tears, cause fracture and, by unloading the cut region, stress concentrations. Failure stress was compared between cracked and control specimens to determine if fracture occurred. Strain concentrations near the crack tip were quantified using digital image correlation (DIC) and used as an indicator of stress concentrations. The presence of cracks did not affect the Meniscus9 failure stress (effect