Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibe... more Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibers with microfibrillar or network-like aggregates and penetrating extrafibrillar proteogly-can matrix. The biomechanical function of the proteoglycan matrix and the collagen fibers are to absorb compressive and tensional loads, respectively. Here, we are focusing on the suprastructural organization of collagen fibrils and the degradation process of their hierarchical organized fiber architecture studied at high resolution at the authentic location within cartilage. We present electron micrographs of the collagenous cores of such fibers obtained by an improved protocol for scanning electron microscopy (SEM). Articular cartilages are permeated by small prototypic fibrils with a homogeneous diameter of 18 ± 5 nm that can align in their D-periodic pattern and merge into larger fibers by lateral association. Interestingly, these fibers have tissue-specific organizations in cartilage. They are twisted ropes in superficial regions of knee joints or assemble into parallel aligned cable-like structures in deeper regions of knee joint-or throughout hip joints articular cartilage. These novel observations contribute to an improved understanding of collagen fiber biogenesis, function, and homeostasis in hyaline cartilage.
Next generation bioreactors are being developed to generate multiple human cell-based tissue anal... more Next generation bioreactors are being developed to generate multiple human cell-based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology [1, 2]. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilagi-nous in nature, while the other is osseous. We next develop a general computational approach to model the microfluidics of a multi-chamber, interconnected system that may be applied to human-on-chip devices. This objective requires overcoming several challenges at the level of computational modeling. The main one consists of addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media. Fluid dynamics is also coupled with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living tissues and C constructs. Ultimately, we aim at providing a predictive approach useful for the general organ-on-chip community. To this end, we have developed a lumped parameter approach that allows us to analyze the behavior of multi-unit bioreactor systems with modest computational effort, provided that the behavior of a single unit can be fully characterized. Data Availability Statement: The manuscript is based on computational models and numerical simulations that are fully reproducible to anyone who has access to the commercial computational platform used for the calculations and named in full details in the manuscript. The authors confirm that there isn't any additional data that is not already provided within the paper.
Purpose: Treatment of meniscus tears is a persistent challenge in orthopaedics. Although cell the... more Purpose: Treatment of meniscus tears is a persistent challenge in orthopaedics. Although cell therapies have shown promise in promoting fibrocartilage formation in in vitro and preclinical studies, clinical application has been limited by the paucity of autologous tissue and the need for ex vivo cell expansion. Rapid dissociation of the free edges of the anterior and posterior meniscus with subsequent implantation in a meniscus lesion may overcome these limitations. The purpose of this study was to explore the effect of rapidly dissociated meniscus tissue in enhancing neotissue formation in a radial meniscus tear, as simulated in an in vitro explant model. Materials and Methods: All experiments in this study, performed at minimum with biological triplicates, utilized meniscal tissues from hind limbs of young cows. The effect of varying collagenase concentration (0.1%, 0.2% and 0.5% w/v) and treatment duration (overnight and 30 minutes) on meniscus cell viability, organization of the extracellular matrix (ECM), and gene expression, was assessed through a cell metabolism assay, microscopic examination, and quantitative real-time reverse transcription polymerase chain reaction analysis, respectively. Thereafter, an explant model of a radial meniscus tear was used to evaluate the effect of a fibrin gel seeded with one of the following – (1) fibrin alone, (2) isolated and passaged (P2) meniscus cells, (3) overnight digested tissue, and (4) rapidly dissociated tissue. The quality of in vitro healing was determined through histological analysis and derivation of an adhesion index. Results: Rapid dissociation in 0.2% collagenase yielded cells with higher levels of metabolism than either 0.1% or 0.5% collagenase. When seeded in a 3-dimensional fibrin hydrogel, both overnight digested and rapidly dissociated cells expressed greater levels of collagens type I and II than P2 meniscal cells at 1 week. At 4 and 8 weeks, collagen type II expression remained elevated only in the rapid dissociation group. Histological examination revealed enhanced healing in all cell-seeded treatment groups over cell-free fibrin controls at weeks 1, 4, and 8, but there were no significant differences across the treatment groups.
Conclusions: Rapid dissociation of meniscus tissue may provide a single-step approach to augment regenerative healing of meniscus repairs.
Single-walled carbon nanotubes (SWNTs) can be labelled with functional moieties that endow them w... more Single-walled carbon nanotubes (SWNTs) can be labelled with functional moieties that endow them with a number of unique characteristics, which can be applicable to biomedical applications such as imaging. Herein we describe a facile, one-step esterification process to functionalize SWNT with fluorescein.
Journal of Biomechanics, Volume 41, Issue null, Pages S169, July 2008, Authors:Riccardo Gottardi;... more Journal of Biomechanics, Volume 41, Issue null, Pages S169, July 2008, Authors:Riccardo Gottardi; Robert Raiteri; Martin Stolz; Robert Kilger; Christian Candrian; Marko Loparic; Sylvie Miot; Marcel Düggelin; Daniel Mathys; Markus Dürrenberger; Laure Aeschimann; Raphael Imer; Urs Staufer; Ivan Martin; Niklaus Friederich; Ueli Aebi.
Bone and cartilage injuries and disorders are observed in a wide range of individuals, from bony ... more Bone and cartilage injuries and disorders are observed in a wide range of individuals, from bony fractures and focal cartilage defects in adolescents, to osteoporosis and osteoarthritis in the elderly. Physical therapists are involved in the treatment of these injuries across the lifespan. While minor injuries to the bone or cartilage can be successfully treated with current surgical or conservative intervention, more extensive injuries, especially those affecting the cartilage, present a challenge to treat. Cartilage injuries often lead to disability and need for invasive surgery later in life. In addition, resection of large amounts of bone or cartilage due to tumors or traumatic injuries will fail to regenerate and require new, innovative strategies to restore tissue loss. Recent advances in the field of tissue regeneration may provide promising treatments for a range of bone and cartilage injuries, and have the potential to positively impact patient function and quality of life....
Amongst their many unique properties, single-walled carbon nanotubes (SWNT) have specific limitat... more Amongst their many unique properties, single-walled carbon nanotubes (SWNT) have specific limitations, including non-uniformity in length, frequent defect sites, and low dispersibility in solution. To overcome these limitations, researchers at the Little Lab developed “zero dimensional” single-walled carbon nanotubes (0dSWNT), less than 10 nm in length and much more dispersible in solution. The aim of this research was to create a more usable form of 0dSWNT by creating thin films using the concept of interfacial film climbing in an oil/water emulsion. Using a heptane/water emulsion, the film-climbing property of the SWNT and 0dSWNT was video-recorded for verification. A pendant drop experiment with nanotubes dispersed in water was used to determine whether a reduction of interfacial tension contributes to film-climbing. Next, thin films of SWNT and 0dSWNT were made on glass slides and coverslips by this technique. As a potential application, SWNT and 0dSWNT thin films on coverslips ...
In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindent... more In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindentation (AFM-DN) tests on the superficial layers of bovine articular cartilage (AC) is provided. The relevant constitutive parameters of the tissue are estimated by fitting experimental results with a finite element model in the frequency domain. Such model comprises a poroelastic stress-strain relationship for a fibril reinforced tissue constitution, assuming a continuous distribution of the collagen network orientations. The identification procedure was first validated using a simplified transversely isotropic constitutive relationship; then, the experimental data were manually fitted by using the continuous distribution fibril model. Tissue permeability is derived from the maximum value of the phase shift between the input harmonic loading and the harmonic tissue response. Tissue parameters related to the stiffness are obtained from the frequency response of the experimental storage modulus and phase shift. With this procedure, an axial to transverse stiffness ratio (anisotropy ratio) of about 0.15 is estimated.
Single-walled carbon nanotubes (SWNTs) can be labeled with functional moieties that endow them wi... more Single-walled carbon nanotubes (SWNTs) can be labeled with functional moieties that endow them with a number of unique characteristics, which can be applicable to biomedical applications such as imaging. Herein we describe a facile, one-step esterification process to functionalize SWNT with fluorescein.
Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibe... more Cartilage matrix is a composite of discrete, but interacting suprastructures, i.e. cartilage fibers with microfibrillar or network-like aggregates and penetrating extrafibrillar proteogly-can matrix. The biomechanical function of the proteoglycan matrix and the collagen fibers are to absorb compressive and tensional loads, respectively. Here, we are focusing on the suprastructural organization of collagen fibrils and the degradation process of their hierarchical organized fiber architecture studied at high resolution at the authentic location within cartilage. We present electron micrographs of the collagenous cores of such fibers obtained by an improved protocol for scanning electron microscopy (SEM). Articular cartilages are permeated by small prototypic fibrils with a homogeneous diameter of 18 ± 5 nm that can align in their D-periodic pattern and merge into larger fibers by lateral association. Interestingly, these fibers have tissue-specific organizations in cartilage. They are twisted ropes in superficial regions of knee joints or assemble into parallel aligned cable-like structures in deeper regions of knee joint-or throughout hip joints articular cartilage. These novel observations contribute to an improved understanding of collagen fiber biogenesis, function, and homeostasis in hyaline cartilage.
Next generation bioreactors are being developed to generate multiple human cell-based tissue anal... more Next generation bioreactors are being developed to generate multiple human cell-based tissue analogs within the same fluidic system, to better recapitulate the complexity and interconnection of human physiology [1, 2]. The effective development of these devices requires a solid understanding of their interconnected fluidics, to predict the transport of nutrients and waste through the constructs and improve the design accordingly. In this work, we focus on a specific model of bioreactor, with multiple input/outputs, aimed at generating osteochondral constructs, i.e., a biphasic construct in which one side is cartilagi-nous in nature, while the other is osseous. We next develop a general computational approach to model the microfluidics of a multi-chamber, interconnected system that may be applied to human-on-chip devices. This objective requires overcoming several challenges at the level of computational modeling. The main one consists of addressing the multi-physics nature of the problem that combines free flow in channels with hindered flow in porous media. Fluid dynamics is also coupled with advection-diffusion-reaction equations that model the transport of biomolecules throughout the system and their interaction with living tissues and C constructs. Ultimately, we aim at providing a predictive approach useful for the general organ-on-chip community. To this end, we have developed a lumped parameter approach that allows us to analyze the behavior of multi-unit bioreactor systems with modest computational effort, provided that the behavior of a single unit can be fully characterized. Data Availability Statement: The manuscript is based on computational models and numerical simulations that are fully reproducible to anyone who has access to the commercial computational platform used for the calculations and named in full details in the manuscript. The authors confirm that there isn't any additional data that is not already provided within the paper.
Purpose: Treatment of meniscus tears is a persistent challenge in orthopaedics. Although cell the... more Purpose: Treatment of meniscus tears is a persistent challenge in orthopaedics. Although cell therapies have shown promise in promoting fibrocartilage formation in in vitro and preclinical studies, clinical application has been limited by the paucity of autologous tissue and the need for ex vivo cell expansion. Rapid dissociation of the free edges of the anterior and posterior meniscus with subsequent implantation in a meniscus lesion may overcome these limitations. The purpose of this study was to explore the effect of rapidly dissociated meniscus tissue in enhancing neotissue formation in a radial meniscus tear, as simulated in an in vitro explant model. Materials and Methods: All experiments in this study, performed at minimum with biological triplicates, utilized meniscal tissues from hind limbs of young cows. The effect of varying collagenase concentration (0.1%, 0.2% and 0.5% w/v) and treatment duration (overnight and 30 minutes) on meniscus cell viability, organization of the extracellular matrix (ECM), and gene expression, was assessed through a cell metabolism assay, microscopic examination, and quantitative real-time reverse transcription polymerase chain reaction analysis, respectively. Thereafter, an explant model of a radial meniscus tear was used to evaluate the effect of a fibrin gel seeded with one of the following – (1) fibrin alone, (2) isolated and passaged (P2) meniscus cells, (3) overnight digested tissue, and (4) rapidly dissociated tissue. The quality of in vitro healing was determined through histological analysis and derivation of an adhesion index. Results: Rapid dissociation in 0.2% collagenase yielded cells with higher levels of metabolism than either 0.1% or 0.5% collagenase. When seeded in a 3-dimensional fibrin hydrogel, both overnight digested and rapidly dissociated cells expressed greater levels of collagens type I and II than P2 meniscal cells at 1 week. At 4 and 8 weeks, collagen type II expression remained elevated only in the rapid dissociation group. Histological examination revealed enhanced healing in all cell-seeded treatment groups over cell-free fibrin controls at weeks 1, 4, and 8, but there were no significant differences across the treatment groups.
Conclusions: Rapid dissociation of meniscus tissue may provide a single-step approach to augment regenerative healing of meniscus repairs.
Single-walled carbon nanotubes (SWNTs) can be labelled with functional moieties that endow them w... more Single-walled carbon nanotubes (SWNTs) can be labelled with functional moieties that endow them with a number of unique characteristics, which can be applicable to biomedical applications such as imaging. Herein we describe a facile, one-step esterification process to functionalize SWNT with fluorescein.
Journal of Biomechanics, Volume 41, Issue null, Pages S169, July 2008, Authors:Riccardo Gottardi;... more Journal of Biomechanics, Volume 41, Issue null, Pages S169, July 2008, Authors:Riccardo Gottardi; Robert Raiteri; Martin Stolz; Robert Kilger; Christian Candrian; Marko Loparic; Sylvie Miot; Marcel Düggelin; Daniel Mathys; Markus Dürrenberger; Laure Aeschimann; Raphael Imer; Urs Staufer; Ivan Martin; Niklaus Friederich; Ueli Aebi.
Bone and cartilage injuries and disorders are observed in a wide range of individuals, from bony ... more Bone and cartilage injuries and disorders are observed in a wide range of individuals, from bony fractures and focal cartilage defects in adolescents, to osteoporosis and osteoarthritis in the elderly. Physical therapists are involved in the treatment of these injuries across the lifespan. While minor injuries to the bone or cartilage can be successfully treated with current surgical or conservative intervention, more extensive injuries, especially those affecting the cartilage, present a challenge to treat. Cartilage injuries often lead to disability and need for invasive surgery later in life. In addition, resection of large amounts of bone or cartilage due to tumors or traumatic injuries will fail to regenerate and require new, innovative strategies to restore tissue loss. Recent advances in the field of tissue regeneration may provide promising treatments for a range of bone and cartilage injuries, and have the potential to positively impact patient function and quality of life....
Amongst their many unique properties, single-walled carbon nanotubes (SWNT) have specific limitat... more Amongst their many unique properties, single-walled carbon nanotubes (SWNT) have specific limitations, including non-uniformity in length, frequent defect sites, and low dispersibility in solution. To overcome these limitations, researchers at the Little Lab developed “zero dimensional” single-walled carbon nanotubes (0dSWNT), less than 10 nm in length and much more dispersible in solution. The aim of this research was to create a more usable form of 0dSWNT by creating thin films using the concept of interfacial film climbing in an oil/water emulsion. Using a heptane/water emulsion, the film-climbing property of the SWNT and 0dSWNT was video-recorded for verification. A pendant drop experiment with nanotubes dispersed in water was used to determine whether a reduction of interfacial tension contributes to film-climbing. Next, thin films of SWNT and 0dSWNT were made on glass slides and coverslips by this technique. As a potential application, SWNT and 0dSWNT thin films on coverslips ...
In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindent... more In this paper, a quantitative interpretation for atomic force microscopy-based dynamic nanoindentation (AFM-DN) tests on the superficial layers of bovine articular cartilage (AC) is provided. The relevant constitutive parameters of the tissue are estimated by fitting experimental results with a finite element model in the frequency domain. Such model comprises a poroelastic stress-strain relationship for a fibril reinforced tissue constitution, assuming a continuous distribution of the collagen network orientations. The identification procedure was first validated using a simplified transversely isotropic constitutive relationship; then, the experimental data were manually fitted by using the continuous distribution fibril model. Tissue permeability is derived from the maximum value of the phase shift between the input harmonic loading and the harmonic tissue response. Tissue parameters related to the stiffness are obtained from the frequency response of the experimental storage modulus and phase shift. With this procedure, an axial to transverse stiffness ratio (anisotropy ratio) of about 0.15 is estimated.
Single-walled carbon nanotubes (SWNTs) can be labeled with functional moieties that endow them wi... more Single-walled carbon nanotubes (SWNTs) can be labeled with functional moieties that endow them with a number of unique characteristics, which can be applicable to biomedical applications such as imaging. Herein we describe a facile, one-step esterification process to functionalize SWNT with fluorescein.
Uploads
Papers by Riccardo Gottardi
Conclusions: Rapid dissociation of meniscus tissue may provide a single-step approach to augment regenerative healing of meniscus repairs.
Keywords: Meniscus, cell therapy, single-step procedure,
Conclusions: Rapid dissociation of meniscus tissue may provide a single-step approach to augment regenerative healing of meniscus repairs.
Keywords: Meniscus, cell therapy, single-step procedure,