Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 75
Filter
1.
Int J Numer Method Biomed Eng ; 40(6): e3821, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38637289

ABSTRACT

Both cell migration and osteogenic differentiation are critical for successful bone regeneration. Therefore, understanding the mechanobiological aspects that govern these two processes is essential in designing effective scaffolds that promote faster bone regeneration. Studying these two factors at different locations is necessary to manage bone regeneration in various sections of a scaffold. Hence, a multiscale computational model was used to observe the mechanical responses of osteoblasts placed in different positions of the trabecular bone and gyroid scaffold. Fluid shear stresses in scaffolds at cell seeded locations (representing osteogenic differentiation) and strain energy densities in cells at cell substrate interface (representing cell migration) were observed as mechanical response parameters in this study. Comparison of these responses, as two critical factors for bone regeneration, between the trabecular bone and gyroid scaffold at different locations, is the overall goal of the study. This study reveals that the gyroid scaffold exhibits higher osteogenic differentiation and cell migration potential compared to the trabecular bone. However, the responses in the gyroid only mimic the trabecular bone in two out of nine positions. These findings can guide us in predicting the ideal cell seeded sites within a scaffold for better bone regeneration and in replicating a replaced bone condition by altering the physical parameters of a scaffold.


Subject(s)
Bone Regeneration , Cancellous Bone , Cell Differentiation , Cell Movement , Osteoblasts , Osteogenesis , Tissue Scaffolds , Bone Regeneration/physiology , Osteoblasts/physiology , Osteoblasts/cytology , Cell Differentiation/physiology , Tissue Scaffolds/chemistry , Cell Movement/physiology , Cancellous Bone/physiology , Osteogenesis/physiology , Humans , Porosity , Models, Biological , Stress, Mechanical
2.
IEEE Trans Pattern Anal Mach Intell ; 46(7): 4944-4956, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38306260

ABSTRACT

Supervised person re-identification (Re-ID) approaches are sensitive to label corrupted data, which is inevitable and generally ignored in the field of person Re-ID. In this paper, we propose a two-stage noise-tolerant paradigm (TSNT) for labeling corrupted person Re-ID. Specifically, at stage one, we present a self-refining strategy to separately train each network in TSNT by concentrating more on pure samples. These pure samples are progressively refurbished via mining the consistency between annotations and predictions. To enhance the tolerance of TSNT to noisy labels, at stage two, we employ a co-training strategy to collaboratively supervise the learning of the two networks. Concretely, a rectified cross-entropy loss is proposed to learn the mutual information from the peer network by assigning large weights to the refurbished reliable samples. Moreover, a noise-robust triplet loss is formulated for further improving the robustness of TSNT by increasing inter-class distances and reducing intra-class distances in the label-corrupted dataset, where a constraint condition for reliability discrimination is carefully designed to select reliable triplets. Extensive experiments demonstrate the superiority of TSNT, for instance, on the Market1501 dataset, our paradigm achieves 90.3% rank-1 accuracy (6.2% improvement over the state-of-the-art method) under noise ratio 20%.

3.
Stem Cell Rev Rep ; 20(3): 755-768, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37971671

ABSTRACT

Mesenchymal to epithelial transition (MET) is instrumental in embryogenesis, tissue repair, and wound healing while the epithelial to mesenchymal transition (EMT) plays role in carcinogenesis. Alteration in microenvironment can modulate cellular signaling and induce EMT and MET. However, modulation of microenvironment to induce MET has been relatively less explored. In this work, effect of matrix stiffness in mediating MET in umbilical cord-derived mesenchymal stem cells (UCMSC) is investigated. Differential segregation of cell fate determinant proteins is one of the key factors in mediating altered stem cell fates through MET even though the genesis of apicobasal polarity remains ambiguous. Herein, it is also attempted to decipher if microenvironment-induced asymmetric cell division has a role to play in driving the cells toward MET. UCMSC cultured on stiffer PDMS matrices resulted in significantly (p < 0.05) higher expression of mechanotransduction proteins. It was also observed that stiffer matrices mediated significant (p < 0.05) upregulation of the polarity proteins and cell fate determinant protein, and epithelial marker proteins over lesser stiff substrates. On the contrary, expression of inflammatory and mesenchymal markers was reduced significantly (p < 0.05) on the stiffer matrices. Cell cycle analysis showed a significant increase in the G1 phase among the cells seeded on stiffer matrices. Transcriptomic studies validated higher expression of epithelial markers genes and lower expression of EMT markers. The transition from mesenchymal to epithelial phenotype depending on the gradation in matrix stiffness is successfully demonstrated. A computational machine learning model was developed to validate stiffness-MET correlation with 94% accuracy. The cross-boundary trans-lineage differentiation capability of MSC on bioengineered substrates can be used as a potential tool in tissue regeneration, organogenesis, and wound healing applications. In our present study, we deciphered the correlation between YAP/TAZ mechanotransduction pathway, EMT signaling pathway, and asymmetric cell division in mediating MET in MSC in a substrate stiffness-dependent manner. It is inferred that the stiffer PDMS matrices facilitate the transition from mesenchymal to epithelial state of MSC. Further, our study also proposed a scoring system to sort MSC from an intermediate hybrid E/M population while undergoing graded MET on matrices of different stiffnesses using a machine learning technique. This proposed scoring system can provide information regarding the E/M state of MSC on different bioengineered constructs based on their biophysical properties which may help in the proper choice of biomaterials in complex tissue-engineering applications.


Subject(s)
Epithelial-Mesenchymal Transition , Mesenchymal Stem Cells , Epithelial-Mesenchymal Transition/genetics , Mechanotransduction, Cellular , Cell Differentiation/genetics , Cell Movement
4.
J Food Sci ; 89(1): 390-403, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38010746

ABSTRACT

An economical and effective storage solution has been designed in this work for the storage of postharvest fruits and vegetables. Musa acuminata or banana has a shelf life of 5-6 days in open uncontrolled environment. This article reports a storage solution of M. acuminata in a controlled enclosure containing titanium oxide (TiO2 )-coated inner walls and irradiated with ultraviolet ray of band "C," an air filtration unit, 5% by volume potassium permanganate (KMnO4 ) solution in a clay pot, grow lights, and activated charcoal granules. The same fruit was kept in an uncontrolled environment too. The percentages of dark spots on banana (M. acuminata) upon storage in controlled and uncontrolled environments have been estimated using an image-processing algorithm. The prediction of dark spots was conducted using multi-linear and multivariate polynomial regression. Experimentation with optimum process parameters obtained with genetic algorithm resulted in a shelf life extension of 6 days as compared to its storage in an uncontrolled environment. The setup can be used in vegetable and fruit markets for the extension of shelf life of postharvest perishable items in a compact and cost-effective manner. The setup does not use any refrigeration process thereby decreasing energy requirement.


Subject(s)
Musa , Environment, Controlled , Fruit/genetics
5.
Proc Inst Mech Eng H ; 237(11): 1297-1305, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37924244

ABSTRACT

Clinical fixation screws are common in clinical practices to fix mandibular condyle fractures. Evidence suggests significance of 'working length' that is, distance between proximal and distal fixation screws in proximity to the fracture in orthopaedic implant design. In pursuit of stable implant-bone construct, this study aims to investigate the biomechanical performance of each configuration considered in the study and provide an optimal working length between the screws for clinical reference. Finite element models of virtually designed broken condyle as type 'B' were simulated and analysed in ANSYS Workbench. Screws are implanted according to previous literature at five varied distances 'd' maintaining five different ratios with the fracture length 'D'. Based on a literature review, boundary conditions, muscle traction forces and non-linear contacts were assigned to obtain precise results. Each case is considered an individual configuration and von Mises distribution, microstrain in bone, screw-bone interface micromotion and fracture dislocation were evaluated for all these configurations. Stress-shielding phenomenon is observed for maximum von Mises stresses in bone. Microstrain concentration was significant in cancellous bone in the vicinity of the screw around the fracture line. Configurations were compared based on the stress-strain along with micromotion to support the required amount of osseointegration between implant and bone. Presented data from all five conditions supported the assumption that under physiological loading conditions, the D3 configuration provided stability for fracture healing. Further research on screw shapes, diameters and material properties, or investigating the direction of forces within the screws could provide further insight into this topic.


Subject(s)
Bone Screws , Fracture Fixation, Internal , Finite Element Analysis , Biomechanical Phenomena , Bone Plates , Cancellous Bone
6.
Front Bioeng Biotechnol ; 11: 1213932, 2023.
Article in English | MEDLINE | ID: mdl-37701494

ABSTRACT

Targeted delivery of site-specific therapeutic agents is an effective strategy for osteoarthritis treatment. The lack of blood vessels in cartilage makes it difficult to deliver therapeutic agents like peptides to the defect area. Therefore, nucleus-targeting zwitterionic carbon nano-dots (CDs) have immense potential as a delivery vehicle for effective peptide delivery to the cytoplasm as well as nucleus. In the present study, nucleus-targeting zwitterionic CDs have been synthesized as delivery vehicle for peptides while also working as nano-agents towards optical monitoring of cartilage healing. The functional groups of zwitterion CDs were introduced by a single-step microwave assisted oxidation procedure followed by COL II peptide conjugation derived from Capra auricular cartilage through NHS/EDC coupling. The peptide-conjugated CDs (PCDs) allows cytoplasmic uptake within a short period of time (∼30 m) followed by translocation to nucleus after ∼24 h. Moreover, multicolor fluorescence of PCDs improves (blue, green, and read channel) its sensitivity as an optical code providing a compelling solution towards enhanced non-invasive tracking system with multifunctional properties. The PCDs-based delivery system developed in this study has exhibited superior ability to induce ex-vivo chondrogenic differentiation of ADMSCs as compared to bare CDs. For assessment of cartilage regeneration potential, pluronic F-127 based PCDs hydrogel was injected to rabbit auricular cartilage defects and potential healing was observed after 60 days. Therefore, the results confirm that PCDs could be an ideal alternate for multimodal therapeutic agents.

7.
IEEE Trans Pattern Anal Mach Intell ; 45(12): 15394-15405, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37773900

ABSTRACT

In many applications, we are constrained to learn classifiers from very limited data (few-shot classification). The task becomes even more challenging if it is also required to identify samples from unknown categories (open-set classification). Learning a good abstraction for a class with very few samples is extremely difficult, especially under open-set settings. As a result, open-set recognition has received limited attention in the few-shot setting. However, it is a critical task in many applications like environmental monitoring, where the number of labeled examples for each class is limited. Existing few-shot open-set recognition (FSOSR) methods rely on thresholding schemes, with some considering uniform probability for open-class samples. However, this approach is often inaccurate, especially for fine-grained categorization, and makes them highly sensitive to the choice of a threshold. To address these concerns, we propose Reconstructing Exemplar-based Few-shot Open-set ClaSsifier (ReFOCS). By using a novel exemplar reconstruction-based meta-learning strategy ReFOCS streamlines FSOSR eliminating the need for a carefully tuned threshold by learning to be self-aware of the openness of a sample. The exemplars, act as class representatives and can be either provided in the training dataset or estimated in the feature domain. By testing on a wide variety of datasets, we show ReFOCS to outperform multiple state-of-the-art methods.

8.
J Biomed Mater Res B Appl Biomater ; 111(12): 2089-2097, 2023 12.
Article in English | MEDLINE | ID: mdl-37624362

ABSTRACT

Total temporomandibular joint (TMJ) replacement is widely recognized as an effective treatment for TMJ disorders. The long-term stability of TMJ implants depends on two important factors which are design concepts for fixation to anatomical locations in the mandible and bone conditions. Other factors include stress distribution, microstrain in the peri-implant, bone attributes like bone conditions leading to the clinical complications and failures. This study addresses these limitations by examining the influence of patient-specific design concepts and bone conditions on TMJ implant performance. Clinical evidences support the importance of implant design on healing ability. Previous studies have focused on achieving precise implant fit based on geometric considerations, however those published studies did not explore the impact of such. Against this perspective, the present study reports the extensive finite element analysis (FEA) results, while analyzing the impact of a newly designed patient-specific TMJ implant to address clinical complications associated with various bone conditions, particularly osteoporotic bone. In validating the FEA results, the performance of additively manufactured patient-specific TMJ implants was compared with designs resembling two commonly used clinically approved implant designs. By addressing the limitations of previous research and emphasizing the importance of bone conditions, the study provides valuable guidelines for the development of next-generation TMJ implants. These findings contribute to enhanced clinical outcomes and long-term success in the treatment of TMJ disorders.


Subject(s)
Bone Diseases , Joint Prosthesis , Temporomandibular Joint Disorders , Humans , Temporomandibular Joint/surgery , Mandible , Temporomandibular Joint Disorders/surgery , Finite Element Analysis , Biomechanical Phenomena , Stress, Mechanical
9.
J R Soc Interface ; 20(203): 20230173, 2023 06.
Article in English | MEDLINE | ID: mdl-37282588

ABSTRACT

In plants, the robust maintenance of tissue structure is crucial to supporting its functionality. The multi-layered shoot apical meristem (SAM) of Arabidopsis, containing stem cells, is an approximately radially symmetric tissue whose shape and structure is maintained throughout the life of the plant. In this paper, a new biologically calibrated pseudo-three-dimensional (P3D) computational model of a longitudinal section of the SAM is developed. It includes anisotropic expansion and division of cells out of the cross-section plane, as well as representation of tension experienced by the SAM epidermis. Results from the experimentally calibrated P3D model provide new insights into maintenance of the structure of the SAM epidermal cell monolayer under tension and quantify dependence of epidermal and subepidermal cell anisotropy on the amount of tension. Moreover, the model simulations revealed that out-of-plane cell growth is important in offsetting cell crowding and regulating mechanical stresses experienced by tunica cells. Predictive model simulations show that tension-determined cell division plane orientation in the apical corpus may be regulating cell and tissue shape distributions needed for maintaining structure of the wild-type SAM. This suggests that cells' responses to local mechanical cues may serve as a mechanism to regulate cell- and tissue-scale patterning.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Meristem/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cell Proliferation , Gene Expression Regulation, Plant , Plant Shoots/metabolism
10.
J Mech Behav Biomed Mater ; 144: 105940, 2023 08.
Article in English | MEDLINE | ID: mdl-37300993

ABSTRACT

Improvement of cell migration by the nano-topographical modification of implant surface can directly or indirectly accelerate wound healing and osseointegration between bone and implant. Therefore, modification of the implant surface was done with TiO2 nanorod (NR) arrays to develop a more osseointegration-friendly implant in this study. Modulating the migration of a cell, adhered to a scaffold, by the variations of NR diameter, density and tip diameter in vitro is the primary objective of the study. The fluid structure interaction method was used, followed by the submodelling technique in this multiscale analysis. After completing a simulation over a global model, fluid structure interaction data was applied to the sub-scaffold finite element model to predict the mechanical response over cells at the cell-substrate interface. Special focus was given to strain energy density at the cell interface as a response parameter due to its direct correlation with the migration of an adherent cell. The results showed a huge rise in strain energy density after the addition of NRs on the scaffold surface. It also highlighted that variation in NR density plays a more effective role than the variation in NR diameter to control cell migration over a substrate. However, the effect of NR diameter becomes insignificant when the NR tip was considered. The findings of this study could be used to determine the best nanostructure parameters for better osseointegration.


Subject(s)
Nanotubes , Titanium , Titanium/chemistry , Nanotubes/chemistry , Osseointegration , Prostheses and Implants
11.
Med Eng Phys ; 112: 103955, 2023 02.
Article in English | MEDLINE | ID: mdl-36842778

ABSTRACT

Anterior Cervical Discectomy and Fusion (ACDF) is the most popular and effective procedure for patients with intervertebral disc degeneration, where the degenerated disc is replaced with an interbody implant (widely known as cage). The design of the cage plays a vital role since it has to provide stability for the anterior cervical column without any side-effects. We designed a novel S-type dynamic cage for C4-C5 level, using Polyetheretherketone (PEEK) material considering four different shapes namely: square, circle, rectangle and elliptical, for the central window to occupy bone graft. The major design constrain for a successful cage is minimized cage stress, in order to avoid subsidence. Finite Element (FE) analysis results revealed that the cage stress values obtained during the physiological motion varied depending upon the shape of the central window provided for bone graft. The objective of this study is to optimize the central window shape using the Teaching Learning Based Optimization (TLBO) algorithm. It was found that square and elliptical shape bone graft cavity resulted in better outcomes. Additional experimental study was also conducted with a six-axis spine simulator. Based on the optimization results, we manufactured two PEEK cage models with square and elliptical shaped central window using additive manufacturing. A prototype model of the C4-C5 level made of Polyvinylchloride (PVC) was used for experiment due to the existing constraints for using a cadaveric model. The experimental results were cross-verified using FE analysis. Thus, we would like to conclude that square and elliptical shape of the central window were the better design factor for our novel dynamic cage.


Subject(s)
Intervertebral Disc , Spinal Fusion , Humans , Finite Element Analysis , Polymers , Benzophenones , Polyethylene Glycols , Ketones , Cervical Vertebrae/surgery , Spinal Fusion/methods , Biomechanical Phenomena
12.
Proc Inst Mech Eng H ; 237(2): 254-264, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36527297

ABSTRACT

The surgical needle insertion process is widely applied in medical interference. During the insertion process, the inhomogeneity and denseness of the soft tissues make it tough to detect the essential tissue damage, a rupture occurs that contains huge forces and material deformations. This study is very important, as all the above-mentioned factors are very significant for modern invasive surgery so that the success rate of the surgery can increase and the patient recovers smoothly. This investigation intends to perform minimally invasive surgical (MIS) procedures and reduce the living tissue damage while performing the biopsy, PCNL, etc. A fracture mechanics method was analyzed to create a needle insertion model which can estimate the needle insertion force during inset in tissue-like PVA gel. The force model was calculated by needle insertion experimentally, and also estimated the needle tip geometry, and diameter influences the fracture toughness. Validate exp. results with simulation results and other papers. It is observed that needle diameter has a significant effect on fracture toughness, whereas the insertion velocity has a slight impact on the fracture toughness. During the rotational needle insertion process, the winds-up of the gel occurs and the diameter of the hole was increasing with increased rpm. Maximum insertion force was noticed in the 27 G needle at 5 mm/s. The interaction function will be less at the maximum fracture development region.


Subject(s)
Biocompatible Materials , Needles , Humans , Mechanical Phenomena , Computer Simulation , Minimally Invasive Surgical Procedures
13.
Int J Artif Organs ; 45(8): 715-721, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35730118

ABSTRACT

The articular disc reduces the stress distribution from the mandible to fossa. In total temporomandibular joint (TMJ) replacement, the implant is required to reduce the stress on fossa implant. Current studies lack standard and optimized parameters for the cylindrical dome on Christensen TMJ implant collar. This study briefed a novel TMJ implant head design and investigates the biomechanical behaviour by considering the articular disc. The radius of the head was varied with the height of the cylinder height to obtain the design of the experiment and the stress distribution was compared with an intact mandible-articular disc model by considering the viscoelastic property of the TMJ disc. The model was simulated at three different angles: 20°, 0° and -20° in the mediolateral direction to simulate the manducation. FEA analysis showed high stresses at the circular heads, and high strength is achieved with increased implant cylinder length and diameter. The results also showed a stress reduction of 50% on the fossa from the mandible. Hence, the newly designed head and suggested modifications may be used as a reference for further clinical improvement of Christensen TMJ as well as other TMJ implants.


Subject(s)
Joint Prosthesis , Mandibular Condyle , Biomechanical Phenomena , Finite Element Analysis , Temporomandibular Joint/surgery , Temporomandibular Joint Disc
14.
PLoS Comput Biol ; 18(6): e1010199, 2022 06.
Article in English | MEDLINE | ID: mdl-35727850

ABSTRACT

Stem cell maintenance in multilayered shoot apical meristems (SAMs) of plants requires strict regulation of cell growth and division. Exactly how the complex milieu of chemical and mechanical signals interact in the central region of the SAM to regulate cell division plane orientation is not well understood. In this paper, simulations using a newly developed multiscale computational model are combined with experimental studies to suggest and test three hypothesized mechanisms for the regulation of cell division plane orientation and the direction of anisotropic cell expansion in the corpus. Simulations predict that in the Apical corpus, WUSCHEL and cytokinin regulate the direction of anisotropic cell expansion, and cells divide according to tensile stress on the cell wall. In the Basal corpus, model simulations suggest dual roles for WUSCHEL and cytokinin in regulating both the direction of anisotropic cell expansion and cell division plane orientation. Simulation results are followed by a detailed analysis of changes in cell characteristics upon manipulation of WUSCHEL and cytokinin in experiments that support model predictions. Moreover, simulations predict that this layer-specific mechanism maintains both the experimentally observed shape and structure of the SAM as well as the distribution of WUSCHEL in the tissue. This provides an additional link between the roles of WUSCHEL, cytokinin, and mechanical stress in regulating SAM growth and proper stem cell maintenance in the SAM.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Cell Wall/metabolism , Computer Simulation , Cytokinins , Gene Expression Regulation, Plant , Homeodomain Proteins/metabolism , Meristem , Plant Shoots
15.
Proc Inst Mech Eng H ; 236(6): 867-881, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35411836

ABSTRACT

Bioprinting using cell-laden bioink is a rapidly emerging additive manufacturing method to fabricate engineered tissue constructs and in vitro models of disease biology. Amongst different bioprinting modalities, extrusion-based bioprinting is the most conveniently adopted technique due to its affordability. Bioinks consisting of living cells are suspended in hydrogels and extruded through syringe-needle assemblies, which subsequently undergo gelation at the collector plate. During the process, pressure is exerted on living cells which may cause cell deaths. Thus, for selected combination of cell and hydrogel, exerted pressure and the extrusion play key roles in determining the cell viability. Experimental evaluation to characterise stresses experienced by the cells in a bioink during bioprinting is a tedious exercise. Herein, computational modelling can be applied efficiently for rapid screening of bioinks. In the present study, a smoothed particle hydrodynamics model is developed for the analysis of stresses exerted on the cells during bioprinting process. Cells are modelled by assigning different mechanical properties to nucleus, cytoskeleton and cell membrane regions of the cell to get a more realistic understanding of cell deformation. The cytoplasm and nucleus are modelled as finite element meshes and a spring model of the cell membrane is coupled to the finite element model to develop a three-compartment model of the cell. Cell deformation is taken as a potential indicator of cell death. Effect of different process parameters such as flow rate, syringe-nozzle geometry and cell density are investigated. A submodeling approach is further introduced to predict deformation with higher resolution in a unit volume containing 104 to 108 cells. Results suggest that the generated bioink flow dynamic model can be a useful tool for the computational study of fluid flow involving cell suspensions during a bioprinting process.


Subject(s)
Bioprinting , Bioprinting/methods , Hydrodynamics , Hydrogels , Printing, Three-Dimensional , Tissue Engineering/methods , Tissue Scaffolds
16.
Rejuvenation Res ; 25(2): 59-69, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35316074

ABSTRACT

Asymmetric division of stem cells is an evolutionarily conserved process in multicellular organisms responsible for maintaining cellular fate diversity. Symmetric-asymmetric division pattern of mesenchymal stem cells (MSCs) is regulated by both biochemical and biophysical cues. However, modulation of mechanotransduction pathway by varying scaffold properties and their adaptation to control stem cell division fate is not widely established. In this study, we explored the interplay between the mechanotransduction pathway and polarity protein complex in stem cell asymmetry under varied biophysical stimuli. We hypothesize that variation of scaffold stiffness will impart mechanical stimulus and control the cytoskeleton assembly through RhoA, which will lead to further downstream activation of polarity-related cell signaling and asymmetric division of MSCs. To establish the hypothesis, umbilical cord-derived MSCs were cultured on polycaprolactone/collagen scaffolds with varied stiffness, and expression levels of several important genes (viz., Yes-associated protein [YAP], transcriptional coactivator with PDZ-binding motif [TAZ], LATS1, LATS2, Par3, Par6, PRKC1 [homolog of aPKC] and RhoA), and biomarkers (viz. YAP, TAZ, F-actin, Numb) were assessed. Support vector machine polarity index was employed to understand the polarization status of the MSCs cultured on varied scaffold stiffness. Furthermore, the Bayesian logistic regression model was employed for classifying the asymmetric division of MSCs cultured on different scaffold stiffnesses that showed 91% accuracy. This study emphasizes the vital role of scaffold properties in modulating the mechanotransduction signaling pathway of MSCs and provides mechanistic basis for adopting facile method to control stem cell division pattern toward improving tissue engineering outcome.


Subject(s)
Mechanotransduction, Cellular , Mesenchymal Stem Cells , Bayes Theorem , Cell Differentiation , Regression Analysis , Stem Cells
17.
Genome Integr ; 13: 2, 2022.
Article in English | MEDLINE | ID: mdl-38021281

ABSTRACT

Our cellular genome is susceptible to cytotoxic lesions which include single strand breaks and double strand breaks among other lesions. Ataxia telangiectasia mutated (ATM) protein was one of the first DNA damage sensor proteins to be discovered as being involved in DNA repair and as well as in telomere maintenance. Telomeres help maintain the stability of our chromosomes by protecting the ends from degradation. Cells from ataxia telangiectasia (AT) patients lack ATM and accumulate chromosomal alterations. AT patients display heightened susceptibility to cancer. In this study, cells from AT patients (called as AT -/- and AT +/- cells) were characterized for genome stability status and it was observed that AT -/- cells show considerable telomere attrition. Furthermore, DNA damage and genomic instability were compared between normal (AT +/+ cells) and AT -/- cells exhibiting increased frequencies of spontaneous DNA damage and genomic instability markers. Both AT -/- and AT +/- cells were sensitive to sodium arsenite (1.5 and 3.0 µg/ml) and ionizing radiation-induced (2 Gy, gamma rays) oxidative stress. Interestingly, telomeric fragments were detected in the comet tails as revealed by comet-fluorescence in situ hybridization analysis, suggestive of telomeric instability in AT -/- cells upon exposure to sodium arsenite or radiation. Besides, there was an increase in the number of chromosome alterations in AT -/- cells following arsenite treatment or irradiation. In addition, complex chromosome aberrations were detected by multicolor fluorescence in situ hybridization in AT -/- cells in comparison to AT +/- and normal cells. Telomere attrition and chromosome alterations were detected even at lower doses of sodium arsenite. Peptide nucleic acid - FISH analysis revealed defective chromosome segregation in cells lacking ATM proteins. The data obtained in this study substantiates the role of ATM in telomere stability under oxidative stress.

18.
Med Biol Eng Comput ; 60(1): 171-187, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34782982

ABSTRACT

The response of cytoskeleton to mechanical cues plays a pivotal role in understanding several aspects of cellular growth, migration, and cell-cell and cell-matrix interactions under normal and diseased conditions. Finite element analysis (FEA) has become a powerful computational technique to study the response of cytoskeleton in the maintenance of overall cellular mechanics. With the revelation of role of external mechanical microenvironment on cell mechanics, FEA models have also been developed to simulate the effect of substrate stiffness on the mechanical properties of cancer cells. However, the models developed so far model cellular response under static mode, whereas in physiological condition, cells always experience dynamic loading conditions. To develop a more accurate model of cell-extracellular matrix (ECM) interactions, this paper models the cytoskeleton and other parts of the cell by beam and solid elements respectively, assuming spherical morphology of the cell. The stiffness and roughness of extracellular matrix were varied. Furthermore, static and dynamic sinusoidal loads were applied through a flat plate indenter on the cell along with providing sinusoidal strain at the substrate. It is observed that due to axial loading, cell reaches a plastic region, and when the sinusoidal loading is added to the axial load, the cell experiences permanent deformation. Degradation of the cytoskeleton elements and a physiologically more relevant spherical cap shape of the cell were also considered during the analysis. This study suggests that asperity topology of the substrate and indirect cyclic load can play a significant role in the shape alterations and motion of a cell.


Subject(s)
Cytoskeleton , Extracellular Matrix , Finite Element Analysis , Models, Biological , Stress, Mechanical , Weight-Bearing
19.
3D Print Addit Manuf ; 9(6): 490-502, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36660750

ABSTRACT

Extrusion-based bioprinting is an enabling biofabrication technique that is used to create heterogeneous tissue constructs according to patient-specific geometries and compositions. The optimization of bioinks as per requirements for specific tissue applications is an essential exercise in ensuring clinical translation of the bioprinting technologies. Most notably, optimum hydrogel polymer concentrations are required to ensure adequate mechanical properties of bioprinted constructs without causing significant shear stresses on cells. However, experimental iterations are often tedious for optimizing the bioink properties. In this work, a nonlinear finite element modeling approach has been undertaken to determine the effect of different bioink parameters such as composition, concentration on the range of stresses being experienced by the cells in the bioprinted construct. The stress distribution of the cells at different parts of the constructs has also been modeled. It is found that both bioink chemical compositions and concentrations can substantially alter the stress effects experienced by the cells. Concentrated regions of softer cells near pore regions were found to increase stress concentrations by almost three times compared with stress generated in cells away from the pores. The study provides a method for rapid optimization of bioinks, design of bioprinted constructs, as well as toolpath plans for fabricating constructs with homogenous properties.

20.
IEEE Trans Image Process ; 30: 8886-8899, 2021.
Article in English | MEDLINE | ID: mdl-34665727

ABSTRACT

Prior works on text-based video moment localization focus on temporally grounding the textual query in an untrimmed video. These works assume that the relevant video is already known and attempt to localize the moment on that relevant video only. Different from such works, we relax this assumption and address the task of localizing moments in a corpus of videos for a given sentence query. This task poses a unique challenge as the system is required to perform: 2) retrieval of the relevant video where only a segment of the video corresponds with the queried sentence, 2) temporal localization of moment in the relevant video based on sentence query. Towards overcoming this challenge, we propose Hierarchical Moment Alignment Network (HMAN) which learns an effective joint embedding space for moments and sentences. In addition to learning subtle differences between intra-video moments, HMAN focuses on distinguishing inter-video global semantic concepts based on sentence queries. Qualitative and quantitative results on three benchmark text-based video moment retrieval datasets - Charades-STA, DiDeMo, and ActivityNet Captions - demonstrate that our method achieves promising performance on the proposed task of temporal localization of moments in a corpus of videos.

SELECTION OF CITATIONS
SEARCH DETAIL
...