scholarly journals Altered swelling and ion fluxes in articular cartilage as a biomarker in osteoarthritis and joint immobilization: a computational analysis

2015 ◽  
Vol 12 (102) ◽  
pp. 20141090 ◽  
Author(s):  
Sara Manzano ◽  
Raquel Manzano ◽  
Manuel Doblaré ◽  
Mohamed Hamdy Doweidar
Keyword(s):  
Articular Cartilage ◽  
Computational Model ◽  
Three Dimensional ◽  
Ion Distribution ◽  
Tissue Degeneration ◽  
Structural Deterioration ◽  
Healthy Cartilage ◽  
Tissue Degradation

In healthy cartilage, mechano-electrochemical phenomena act together to maintain tissue homeostasis. Osteoarthritis (OA) and degenerative diseases disrupt this biological equilibrium by causing structural deterioration and subsequent dysfunction of the tissue. Swelling and ion flux alteration as well as abnormal ion distribution are proposed as primary indicators of tissue degradation. In this paper, we present an extension of a previous three-dimensional computational model of the cartilage behaviour developed by the authors to simulate the contribution of the main tissue components in its behaviour. The model considers the mechano-electrochemical events as concurrent phenomena in a three-dimensional environment. This model has been extended here to include the effect of repulsion of negative charges attached to proteoglycans. Moreover, we have studied the fluctuation of these charges owning to proteoglycan variations in healthy and pathological articular cartilage. In this sense, standard patterns of healthy and degraded tissue behaviour can be obtained which could be a helpful diagnostic tool. By introducing measured properties of unhealthy cartilage into the computational model, the severity of tissue degeneration can be predicted avoiding complex tissue extraction and subsequent in vitro analysis. In this work, the model has been applied to monitor and analyse cartilage behaviour at different stages of OA and in both short (four, six and eight weeks) and long-term (11 weeks) fully immobilized joints. Simulation results showed marked differences in the corresponding swelling phenomena, in outgoing cation fluxes and in cation distributions. Furthermore, long-term immobilized patients display similar swelling as well as fluxes and distribution of cations to patients in the early stages of OA, thus, preventive treatments are highly recommended to avoid tissue deterioration.

scholarly journals Modelling human skull growth: a validated computational model

2017 ◽  
Vol 14 (130) ◽  
pp. 20170202 ◽  
Author(s):  
Joseph Libby ◽  
Arsalan Marghoub ◽  
David Johnson ◽  
Roman H. Khonsari ◽  
Michael J. Fagan ◽  
...  
Keyword(s):  
Computational Model ◽  
Three Dimensional ◽  
Basic Knowledge ◽  
Fe Model ◽  
Adult Size ◽  
Fe Method ◽  
Percentage Difference ◽  
Skull Growth

During the first year of life, the brain grows rapidly and the neurocranium increases to about 65% of its adult size. Our understanding of the relationship between the biomechanical forces, especially from the growing brain, the craniofacial soft tissue structures and the individual bone plates of the skull vault is still limited. This basic knowledge could help in the future planning of craniofacial surgical operations. The aim of this study was to develop a validated computational model of skull growth, based on the finite-element (FE) method, to help understand the biomechanics of skull growth. To do this, a two-step validation study was carried out. First, an in vitro physical three-dimensional printed model and an in silico FE model were created from the same micro-CT scan of an infant skull and loaded with forces from the growing brain from zero to two months of age. The results from the in vitro model validated the FE model before it was further developed to expand from 0 to 12 months of age. This second FE model was compared directly with in vivo clinical CT scans of infants without craniofacial conditions ( n = 56). The various models were compared in terms of predicted skull width, length and circumference, while the overall shape was quantified using three-dimensional distance plots. Statistical analysis yielded no significant differences between the male skull models. All size measurements from the FE model versus the in vitro physical model were within 5%, with one exception showing a 7.6% difference. The FE model and in vivo data also correlated well, with the largest percentage difference in size being 8.3%. Overall, the FE model results matched well with both the in vitro and in vivo data. With further development and model refinement, this modelling method could be used to assist in preoperative planning of craniofacial surgery procedures and could help to reduce reoperation rates.

Long-term in vitro human pancreatic islet culture using three-dimensional microfabricated scaffolds

Biomaterials ◽  
2011 ◽  
Vol 32 (6) ◽  
pp. 1536-1542 ◽  
Author(s):  
Jamal T. Daoud ◽  
Maria S. Petropavlovskaia ◽  
Jason M. Patapas ◽  
Christian E. Degrandpré ◽  
Robert W. DiRaddo ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Three Dimensional ◽  
Human Pancreatic Islet ◽  
Islet Culture

Hydroxyapatite (HA) stimulates murine periosteal clonal cells to develop osteoblastic–clastic phenotype favoring its own reabsorption after long-term three-dimensional in vitro culture

Bone ◽  
2011 ◽  
Vol 48 ◽  
pp. S130
Author(s):  
F. Ferro ◽  
R. Spelat ◽  
F. D'Aurizio ◽  
G. Falini ◽  
I. De Pol ◽  
...  
Keyword(s):  
In Vitro Culture ◽  
Three Dimensional

scholarly journals A Computational Model of Bidirectional Axonal Growth in Micro-Tissue Engineered Neuronal Networks (micro-TENNs)

2018 ◽  
Author(s):  
Toma Marinov ◽  
Liang Yuchi ◽  
Dayo O. Adewole ◽  
D. Kacy Cullen ◽  
Reuben H. Kraft
Keyword(s):  
White Matter ◽  
Computational Model ◽  
Large Scale ◽  
Three Dimensional ◽  
Growth Conditions ◽  
Growth Time ◽  
Directional Growth ◽  
System Reconstruction ◽  
Realistic Neuron

AbstractMicro-Tissue Engineered Neural Networks (Micro-TENNs) are living three-dimensional constructs designed to replicate the neuroanatomy of white matter pathways in the brain, and are being developed as implantable microtissue for axon tract reconstruction or as anatomically-relevant in vitro experimental platforms. Micro-TENNs are composed of discrete neuronal aggregates connected by bundles of long-projecting axonal tracts within miniature tubular hydrogels. In order to help design and optimize micro-TENN performance, we have created a new computational model including geometric and functional properties. The model is built upon the three-dimensional diffusion equation and incorporates large-scale uni- and bi-directional growth that simulates realistic neuron morphologies. The model captures unique features of 3D axonal tract development that are not apparent in planar outgrowth, and may be insightful for how white matter pathways form during brain development. The processes of axonal outgrowth, branching, turning and aggregation/bundling from each neuron are described through functions built on concentration equations and growth time distributed across the growth segments. Once developed we conducted multiple parametric studies to explore the applicability of the method and conducted preliminary validation via comparisons to experimentally grown micro-TENNs for a range of growth conditions. Using this framework, this model can be applied to study micro-TENN growth processes and functional characteristics using spiking network or compartmental network modeling. This model may be applied to improve our understanding of axonal tract development and functionality, as well as to optimize the fabrication of implantable tissue engineered brain pathways for nervous system reconstruction and/or modulation.

scholarly journals Cryopreserved, Thin, Laser-Etched Osteochondral Allograft Maintains the Functional Components of Articular Cartilage After Two Years of Storage

2020 ◽  
Author(s):  
Carolyn B Rorick ◽  
Jordyn A Mitchell ◽  
Ruth H Bledsoe ◽  
Michael L Floren ◽  
Ross M Wilkins
Keyword(s):  
Flow Cytometry ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Treatment Options ◽  
Osteochondral Allograft ◽  
Protein Signaling ◽  
Chondral Defects ◽  
Healthy Cartilage ◽  
Functional Components

Abstract Background : Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair. Methods: Viability testing was performed by digestion of the graft, cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro . Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage. Results: Average viability of the T-LE Allograft post-thaw was found to be 94.97 ±3.38%, compared to 98.83 ±0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers. Conclusions: Using our novel, proprietary cryopreservation method, the T-LE Allograft retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after two years of storage at -80 o C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.

scholarly journals Cryopreserved, Thin, Laser-Etched Osteochondral Allograft Maintains the Functional Components of Articular Cartilage After Two Years of Storage

2020 ◽  
Author(s):  
Carolyn B Rorick ◽  
Jordyn A Mitchell ◽  
Ruth H Bledsoe ◽  
Michael L Floren ◽  
Ross M Wilkins
Keyword(s):  
Flow Cytometry ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Treatment Options ◽  
Osteochondral Allograft ◽  
Protein Signaling ◽  
Chondral Defects ◽  
Healthy Cartilage ◽  
Functional Components

Abstract Background : Despite improvements in treatment options and techniques, articular cartilage repair continues to be a challenge for orthopedic surgeons. This study provides data to support that the 2-year Cryopreserved, Thin, Laser-Etched Osteochondral Allograft (T-LE Allograft) embodies the necessary viable cells, protein signaling, and extracellular matrix (ECM) scaffold found in fresh cartilage in order to facilitate a positive clinical outcome for cartilage defect replacement and repair. Methods: Viability testing was performed by digestion of the graft, cells were counted using a trypan blue assay. Growth factor and ECM protein content was quantified using biochemical assays. A fixation model was introduced to assess tissue outgrowth capability and cellular metabolic activity in vitro . Histological and immunofluorescence staining were employed to confirm tissue architecture, cellular outgrowth, and presence of ECM. The effects of the T-LE Allograft to signal bone marrow-derived mesenchymal stem cell (BM-MSC) migration and chondrogenic differentiation were evaluated using in vitro co-culture assays. Immunogenicity testing was completed using flow cytometry analysis of cells obtained from digested T-LE Allografts and fresh articular cartilage. Results: Average viability of the T-LE Allograft post-thaw was found to be 94.97 ±3.38%, compared to 98.83 ±0.43% for fresh articular cartilage. Explant studies from the in vitro fixation model confirmed the long-term viability and proliferative capacity of these chondrocytes. Growth factor and ECM proteins were quantified for the T-LE Allograft revealing similar profiles to fresh articular cartilage. Cellular signaling of the T-LE Allograft and fresh articular cartilage both exhibited similar outcomes in co-culture for migration and differentiation of BM-MSCs. Flow cytometry testing confirmed the T-LE Allograft is immune-privileged as it is negative for immunogenic markers and positive for chondrogenic markers. Conclusions: Using our novel, proprietary cryopreservation method, the T-LE Allograft retains excellent cellular viability, with native-like growth factor and ECM composition of healthy cartilage after two years of storage at -80 o C. The successful cryopreservation of the T-LE Allograft alleviates the limited availably of conventionally used fresh osteochondral allograft (OCA), by providing a readily available and simple to use allograft solution. The results presented in this paper supports clinical data that the T-LE Allograft can be a successful option for repairing chondral defects.

Long Term Effect of P188 on Meniscus Preservation Following Blunt Trauma

2012 ◽  
Author(s):  
Adam C. Abraham ◽  
Megan L. Killian ◽  
Roger C. Haut ◽  
Tammy L. Haut Donahue
Keyword(s):  
Cell Death ◽  
Articular Cartilage ◽  
Early Stage ◽  
Subsequent Treatment ◽  
Joint Injury ◽  
Secondary Osteoarthritis ◽  
Tissue Degeneration ◽  
Long Term Effect ◽  
Tissue Matrix

Acute knee joint injury has been associated with the development and progression of secondary osteoarthritis (OA). Previous work implicates that acute damage to tissue matrix and cells of the meniscus and articular cartilage may play important roles in early-stage OA [1]. Additionally, it has been shown that articular cartilage matrix repair hinges on chondrocyte preservation [2]. Therefore, inhibition of cell death may halt tissue degeneration. Recently, the FDA-approved surfactant Poloxamer 188 (P-188) has been shown to decrease acute cell death by repair of its plasma membrane, as well as mediate p38 signaling and subsequent inflammatory and apoptotic signaling leading to a reduction in degeneration of impacted cartilage [3, 4]. Therefore, it was hypothesized that matrix glycosaminoglycans of the meniscus will be preserved in the long-term following traumatic impaction and subsequent treatment with P-188.

A Device for Long Term, In Vitro Loading of Three-Dimensional Natural and Engineered Tissues

2003 ◽  
Vol 31 (11) ◽  
pp. 1347-1356 ◽  
Author(s):  
Daniel A. Shimko ◽  
Kyle K. White ◽  
Eric A. Nauman ◽  
Kay C Dee
Keyword(s):  
Three Dimensional ◽  
Engineered Tissues

scholarly journals The Bordetella Bps Polysaccharide Is Critical for Biofilm Development in the Mouse Respiratory Tract

2007 ◽  
Vol 189 (22) ◽  
pp. 8270-8276 ◽  
Author(s):  
Gina Parise Sloan ◽  
Cheraton F. Love ◽  
Neelima Sukumar ◽  
Meenu Mishra ◽  
Rajendar Deora
Keyword(s):  
Whooping Cough ◽  
Three Dimensional ◽  
Respiratory Pathogens ◽  
Adolescents And Adults ◽  
The Stability ◽  
Inert Surfaces ◽  
Biofilm Development

ABSTRACT Bordetellae are respiratory pathogens that infect both humans and animals. Bordetella bronchiseptica establishes asymptomatic and long-term to life-long infections of animal nasopharynges. While the human pathogen Bordetella pertussis is the etiological agent of the acute disease whooping cough in infants and young children, it is now being increasingly isolated from the nasopharynges of vaccinated adolescents and adults who sometimes show milder symptoms, such as prolonged cough illness. Although it has been shown that Bordetella can form biofilms in vitro, nothing is known about its biofilm mode of existence in mammalian hosts. Using indirect immunofluorescence and scanning electron microscopy, we examined nasal tissues from mice infected with B. bronchiseptica. Our results demonstrate that a wild-type strain formed robust biofilms that were adherent to the nasal epithelium and displayed architectural attributes characteristic of a number of bacterial biofilms formed on inert surfaces. We have previously shown that the Bordetella Bps polysaccharide encoded by the bpsABCD locus is critical for the stability and maintenance of three-dimensional structures of biofilms. We show here that Bps is essential for the formation of efficient nasal biofilms and is required for the colonization of the nose. Our results document a biofilm lifestyle for Bordetella in mammalian respiratory tracts and highlight the essential role of the Bps polysaccharide in this process and in persistence of the nares.

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