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1.
J Biomed Mater Res A ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630051

RESUMO

Despite the attractive combinations of cell/surface interactions, biocompatibility, and good mechanical properties of Ti-6Al-4V, there is still a need to enhance the early stages of cell/surface integration that are associated with the implantation of biomedical devices into the human body. This paper presents a novel, easy and reproducible method of nanoscale and nanostructured hydroxyapatite (HA) coatings on Ti-6Al-4V. The resulting nanoscale coatings/nanostructures are characterized using a combination of Raman spectroscopy, scanning electron microscopy equipped with energy dispersive x-ray spectroscopy. The nanostructured/nanoscale coatings are shown to enhance the early stages of cell spreading and integration of bone cells (hFOB cells) on Ti-6Al-4V surfaces. The improvements include the acceleration of extra-cellular matrix, cell spreading and proliferation by nanoscale HA structures on the coated surfaces. The implications of the results are discussed for the development of HA nanostructures for the improved osseointegration of Ti-6Al-4V in orthopedic and dental applications.

2.
J Mater Sci Mater Med ; 34(8): 41, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37530973

RESUMO

The paper presents the results of the experimental and analytical study of targeted drug-loaded polymer-based microspheres made from blend polymer of polylactic-co-glycolic acid and polycaprolactone (PLGA-PCL) for targeted and localized cancer drug delivery. In vitro sustained release with detailed thermodynamically driven drug release kinetics, over a period of three months using encapsulated targeted drugs (prodigiosin-EphA2 or paclitaxel-EphA2) and control drugs [Prodigiosin (PGS), and paclitaxel (PTX)] were studied. Results from in vitro study showed a sustained and localized drug release that is well-characterized by non-Fickian Korsmeyer-Peppas kinetics model over the range of temperatures of 37 °C (body temperature), 41 °C, and 44 °C (hyperthermic temperatures). The in vitro alamar blue, and flow cytometry assays in the presence of the different drug-loaded polymer formulations resulted to cell death and cytotoxicity that was evidence through cell inhibition and late apoptosis on triple negative breast cancer (TNBC) cells (MDA-MB 231). In vivo studies carried out on groups of 4-week-old athymic nude mice that were induced with subcutaneous TNBC, showed that the localized release of the EphA2-conjugated drugs was effective in complete elimination of residual tumor after local surgical resection. Finally, ex vivo histopathological analysis carried out on the euthanized mice revealed no cytotoxicity and absence of breast cancer metastases in the liver, kidney, and lungs 12 weeks after treatment. The implications of the results are then discussed for the development of encapsulated EphA2-conjugated drugs formulation in the specific targeting, localized, and sustain drug release for the elimination of local recurred TNBC tumors after surgical resection.


Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Camundongos , Animais , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Prodigiosina , Microesferas , Camundongos Nus , Linhagem Celular Tumoral , Paclitaxel/farmacologia , Polímeros
3.
Environ Monit Assess ; 195(8): 984, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37486547

RESUMO

Machine learning (ML) models have become a potent tool for advancing environmentally conscious research in materials science, allowing the prediction of wastewater treatment efficacy using eco-materials. In this study, we showcase the potential of an advanced decision tree-based ensemble learning algorithm to model the eviction of emerging organophosphate-based pesticidal pollutants in aqueous systems. The model is trained using laboratory-based biochar adsorption data, and it establishes the relationship between independent experimental factors and the % organophosphate pesticide adsorption efficiency as the output parameter. We classified the experimental dataset into input and output parameters to build the model. The input parameters included pyrolysis temperature, solution pH, surface area, pore volume, and initial pesticide concentration. Grid search optimization in Python was employed to train the model using sets of input-output patterns. The results indicated that the XGBoost-based ensemble ML framework provides the best forecast for pesticide adsorption on the biochar matrix, achieving high scores for the regularization coefficient (R2train = 0.998, R2test = 0.981). The concentration of the organophosphorus compound and the morphology of biochar significantly influenced the pesticide adsorption behavior. These findings demonstrate the potential of using ensemble learning algorithms for the balanced design of carbon-enriched biomaterials to remove emerging micropollutants from water effectively.


Assuntos
Inseticidas , Praguicidas , Poluentes Químicos da Água , Compostos Organofosforados , Adsorção , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Carvão Vegetal/química , Aprendizado de Máquina , Organofosfatos , Cinética
4.
J Vis Exp ; (195)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37318252

RESUMO

Irregular biomechanics are a hallmark of cancer biology subject to extensive study. The mechanical properties of a cell are similar to those of a material. A cell's resistance to stress and strain, its relaxation time, and its elasticity are all properties that can be derived and compared to other types of cells. Quantifying the mechanical properties of cancerous (malignant) versus normal (non-malignant) cells allows researchers to further uncover the biophysical fundamentals of this disease. While the mechanical properties of cancer cells are known to consistently differ from the mechanical properties of normal cells, a standard experimental procedure to deduce these properties from cells in culture is lacking. This paper outlines a procedure to quantify the mechanical properties of single cells in vitro using a fluid shear assay. The principle behind this assay involves applying fluid shear stress onto a single cell and optically monitoring the resulting cellular deformation over time. Cell mechanical properties are subsequently characterized using digital image correlation (DIC) analysis and fitting an appropriate viscoelastic model to the experimental data generated from the DIC analysis. Overall, the protocol outlined here aims to provide a more effective and targeted method for the diagnosis of difficult-to-treat cancers.


Assuntos
Fenômenos Biomecânicos , Elasticidade , Estresse Mecânico , Viscosidade
5.
J Mech Behav Biomed Mater ; 142: 105831, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37075528

RESUMO

This study investigates the compressive deformation and the effect of structural architecture on the compressive strength of bioprocessed mycelium biocomposites reinforced with laterite particles. In the mycelium blocks, lignocellulosic hemp hurds function as reinforcing and nutritional substrates. The mycelium acts as a supportive matrix, binding the hemp hurds and the laterite particles which are integrated for further reinforcement to improve the compressive strength of the composite. The compressive behavior of the composites is elucidated using a combined approach of experimental and theoretical studies. The deformation mechanisms are investigated via in-situ observations of the specimens under uniaxial compressive loading. The experiments show that the compressive deformation results in progressive micro-buckling in slender specimens, whereas thicker samples exhibit a soft elastic response at small strain levels followed by continuous stiffening at larger strains. Based on the experimental observations and the morphological characterization, a column buckling analysis was developed for the mycelium-hemp composites to further explain the observed deformation phenomena.


Assuntos
Modelos Teóricos , Micélio , Micélio/química , Força Compressiva , Pressão
6.
Acta Biomater ; 158: 374-392, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36640950

RESUMO

This paper presents the results of a combined experimental and theoretical study of the structure and viscoelastic properties of human non-tumorigenic mammary breast tissues and triple negative breast cancer (TNBC) tissues of different histological grades. A combination of immunofluorescence and confocal microscopy, and atomic force microscopy is used to study the actin cytoskeletal structures of non-tumorigenic and tumorigenic breast tissues (grade I to grade III). A combination of nanoindentation and statistical techniques is then used to measure viscoelastic properties of non-tumorigenic and human TNBC of different histological grades. A Standard Fluid Model/Anti-Zener Model II is also used to characterize the viscoelastic properties of the non-tumorigenic and tumorigenic TNBC tissues of different grades. The implications of the results are discussed for the potential application of nanoindentation and statistical deconvolution techniques to the development of mechanical biomarkers for TNBC detection/cancer diagnosis. STATEMENT OF SIGNIFICANCE: There is increasing interest in the development of mechanical biomarkers for cancer diagnosis. Here, we show that nanoindentation techniques can be used to characterize the viscoelastic properties of normal breast tissue and TNBC tissues of different histological grades. The Standard Fluid Model (Anti-Zener Model II) is used to classify the viscoelastic properties of breast tissues of different TNBC histological grades. Our results suggest that breast tissue and TNBC tissue viscoelastic properties can be used as mechanical biomarkers for the detection of TNBC at different stages.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , Mama , Biomarcadores Tumorais , Citoesqueleto
7.
J Biomed Mater Res B Appl Biomater ; 111(3): 665-683, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36314600

RESUMO

This article presents silica nanoparticles for the sustained release of AMACR antibody-conjugated and free doxorubicin (DOX) for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with phenylboronic acid groups (MCM-B), and capped with dextran (MCM-B-D). The nanoparticles were then characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, zeta potential analysis, nitrogen sorption, X-ray diffraction, and thermogravimetric analysis, before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, DOX, and a targeted prostate cancer drug, α-Methyl Acyl-CoA racemase (AMACR) antibody-conjugated DOX, which attaches specifically to AMACR proteins that are overexpressed on the surfaces of prostate cancer cells. The kinetics of sustained drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer-Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR antibody-conjugated DOX drug-loaded nanoparticles were more effective than the free DOX drug-loaded formulations in inhibiting the growth of prostate cancer cells in vitro over a 96 h period. The implications of the results are then discussed for the development of drug-eluting structures for the localized and targeted treatment of prostate cancer.


Assuntos
Nanopartículas , Neoplasias da Próstata , Humanos , Masculino , Preparações de Ação Retardada/farmacologia , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanopartículas/química , Neoplasias da Próstata/tratamento farmacológico , Racemases e Epimerases/uso terapêutico , Dióxido de Silício/farmacologia , Dióxido de Silício/química
8.
J Mech Behav Biomed Mater ; 136: 105461, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36195050

RESUMO

The adhesive interactions between molecular recognition units (such as specific peptides and antibodies) and antigens or other receptors on the surfaces of tumors are of great value in the design of targeted nanoparticles and drugs for the detection and treatment of specific cancers. In this paper, we present the results of a combined experimental and theoretical study of the adhesion between Luteinizing Hormone Releasing Hormone (LHRH)/Epherin type A2 (EphA2)-AFM coated tips and LHRH/EphA2 receptors that are overexpressed on the surfaces of human Triple Negative Breast Cancer (TNBC) tissues of different histological grades. Following a histochemical and immuno-histological study of human tissue extracts, the receptor overexpression, and their distributions are characterized using Immunohistochemistry (IHC), Immunofluorescence (IF), and a combination of fluorescence microscopy and confocal microscopy. The adhesion forces between LHRH or EphA2 and human TNBC breast tissues are measured using force microscopy techniques that account for the potential effects of capillary forces due to the presence of water vapor. The corresponding adhesion energies are also determined using adhesion theory. The pull off forces and adhesion energies associated with higher grades of TNBC are shown to be greater than those associated with normal/non-tumorigenic human breast tissues, which were studied as controls. The observed increase in adhesion forces and adhesion energies are also correlated with the increasing incidence of LHRH/EphA2 receptors at higher grades of TNBC. The implications of the results are discussed for the development of targeted nanostructures for the detection and treatment of TNBC.


Assuntos
Hormônio Liberador de Gonadotropina , Receptores LHRH , Neoplasias de Mama Triplo Negativas , Humanos , Linhagem Celular Tumoral , Hormônio Liberador de Gonadotropina/química , Nanopartículas , Receptores LHRH/química , Neoplasias de Mama Triplo Negativas/patologia
9.
Biomater Adv ; 136: 212801, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35929297

RESUMO

This paper presents the results of an experimental and computational study of the adhesion of triptorelin-conjugated PEG-coated biosynthesized gold nanoparticles (GNP-PEG-TRP) to triple-negative breast cancer (TNBC) cells. The adhesion is studied at the nanoscale using a combination of atomic force microscopy (AFM) experiments and molecular dynamics (MD) simulations. The AFM measurements showed that the triptorelin-functionalized gold nanoparticles (GNP-TRP and GNP-PEG-TRP) have higher adhesion to triple-negative breast cancer cells (TNBC) than non-tumorigenic breast cells. The increased adhesion of GNP-TRP and GNP-PEG-TRP to TNBC is also attributed to the overexpression of LHRH receptors on the surfaces of both TNBC. Finally, the molecular dynamics model reveals insights into the effects of receptor density, molecular configuration, and receptor-ligand docking characteristics on the interactions of triptorelin-functionalized PEG-coated gold nanoparticles with TNBC. A three to nine-fold increase in the adhesion is predicted between triptorelin-functionalized PEG-coated gold nanoparticles and TNBC cells. The implications of the results are then discussed for the specific targeting of TNBC.


Assuntos
Nanopartículas Metálicas , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Ouro/farmacologia , Humanos , Ligantes , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Pamoato de Triptorrelina/farmacologia
10.
J Biomed Mater Res B Appl Biomater ; 110(12): 2727-2743, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35799416

RESUMO

This paper presents the results of an experimental and computational study of the effects of laser-induced heating provided by magnetite nanocomposite structures that are being developed for the localized hyperthermic treatment of triple-negative breast cancer. Magnetite nanoparticle-reinforced polydimethylsiloxane (PDMS) nanocomposites were fabricated with weight percentages of 1%, 5%, and 10% magnetite nanoparticles. The nanocomposites were exposed to incident Near Infrared (NIR) laser beams with well-controlled powers. The laser-induced heating is explored in: (i) heating liquid media (deionized water and cell growth media [Leibovitz L15+]) to characterize the photothermal properties of the nanocomposites, (ii) in vitro experiments that explore the effects of localized heating on triple-negative breast cancer cells, and (iii) experiments in which the laser beams penetrate through chicken tissue to heat up nanocomposite samples embedded at different depths beneath the chicken skin. The resulting plasmonic laser-induced heating is explained using composite theories and heat transport models. The results show that the laser/nanocomposite interactions decrease the viability of triple-negative breast cancer cells (MDA-MB-231) at temperatures in the hyperthermia domain between 41 and 44°C. Laser irradiation did not cause any observed physical damage to the chicken tissue. The potential in vivo performance of the PDMS nanocomposites was also investigated using computational finite element models of the effects of laser/magnetite nanocomposite interactions on the temperatures and thermal doses experienced by tissues that surround the nanocomposite devices. The implications of the results are then discussed for the development of implantable nanocomposite devices for localized treatment of triple-negative breast cancer tissue via hyperthermia.


Assuntos
Hipertermia Induzida , Nanocompostos , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Proliferação de Células , Dimetilpolisiloxanos , Óxido Ferroso-Férrico/química , Calefação , Humanos , Hipertermia Induzida/métodos , Lasers , Nanocompostos/química , Neoplasias de Mama Triplo Negativas/terapia , Água
11.
Sci Rep ; 12(1): 12860, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896576

RESUMO

In this paper, we use Polyethylene Oxide (PEO) particles to control the morphology of Formamidinium (FA)-rich perovskite films and achieve large grains with improved optoelectronic properties. Consequently, a planar perovskite solar cell (PSC) is fabricated with additions of 5 wt% of PEO, and the highest PCE of 18.03% was obtained. This solar cell is also shown to retain up to 80% of its initial PCE after about 140 h of storage under the ambient conditions (average relative humidity of 62.5 ± 3.25%) in an unencapsulated state. Furthermore, the steady-state PCE of the PEO-modified PSC device remained stable for long (over 2500 s) under continuous illumination. This addition of PEO particles is shown to enable the tuning of the optoelectronic properties of perovskite films, improvements in the overall photophysical properties of PSCs, and an increase in resistance to the degradation of PSCs.

12.
J Biomed Mater Res A ; 110(5): 1004-1020, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34967111

RESUMO

This article presents the correlation of creep and viscoelastic properties to the cytoskeletal structure of both tumorigenic and non-tumorigenic cells. Unique shear assay and strain mapping techniques were used to study the creep and viscoelastic properties of single non-tumorigenic and tumorigenic cells. At least 20 individual cells, three locations per cell, were studied. From the results, lower densities in the volume of actin, and keratin 18 structures were observed with the progression of cancer and were correlated to the increased creep rates and reduced mechanical properties (Young's moduli and viscosities) of tumorigenic (MDA-MB-231) cells. The study reveals significant differences between the creep and viscoelastic properties of non-tumorigenic breast cells versus tumorigenic cells. The variations in the creep strain rates are shown to be well characterized by lognormal distributions, while the statistical variations in the viscoelastic properties are well-described by normal distributions. The implications of the results are discussed for the study of discrete cell behaviors, strain and viscoelastic responses of the cell, and the role of cell cytoskeleton in the onset and progression of cancers.


Assuntos
Neoplasias de Mama Triplo Negativas , Actinas , Citoesqueleto , Módulo de Elasticidade , Elasticidade , Humanos , Viscosidade
13.
IEEE Robot Autom Lett ; 6(3): 4664-4671, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34532570

RESUMO

Novel severe acute respiratory syndrome coronavirus 2 (COVID-19) has become a pandemic of epic proportions, and global response to prepare health systems worldwide is of utmost importance. 2-dimensional (2D) lung ultrasound (LUS) has emerged as a rapid, noninvasive imaging tool for diagnosing COVID-19 infected patients. Concerns surrounding LUS include the disparity of infected patients and healthcare providers, and importantly, the requirement for substantial physical contact between the patient and operator, increasing the risk of transmission. New variants of COVID-19 will continue to emerge; therefore, mitigation of the virus's spread is of paramount importance. A tele-operative robotic ultrasound platform capable of performing LUS in COVID-19 infected patients may be of significant benefit, especially in low- and middle-income countries. The authors address the issues mentioned above surrounding the use of LUS in COVID-19 infected patients and the potential for extension of this technology in a resource-limited environment. Additionally, first-time application, feasibility, and safety were validated in healthy subjects. Preliminary results demonstrate that our platform allows for the successful acquisition and application of robotic LUS in humans.

14.
J Biomed Mater Res A ; 109(12): 2611-2624, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34180577

RESUMO

This article presents the results of cell-surface interactions on polydimethylsiloxane (PDMS)-based substrates coated with nanoscale gold (Au) thin films. The surfaces of PDMS and PDMS-magnetite (MNP)-based substrates were treated with UV-ozone, prior to thermal vapor deposition (sputter-coated) of thin films of titanium (Ti) onto the substrates to improve the adhesion of Au coatings. The thin layer of Ti was thermally evaporated to improve interfacial adhesion, which was enhanced by a 40-nm thick film microwrinkled/buckled wavy layer of Au, that was coated to enhance cell-surface interactions and protein absorption. Cell-surface interactions were studied on the hybrid surfaces using a combination of optical and fluorescence microscopy. Consequently, cell proliferation and surface cytotoxicity (of the sputter-coated PDMS surfaces) were elucidated by characterizing the metabolic activity in the presence of breast cancer and normal breast cells. The photothermal conversion efficiency associated with laser-materials interactions with the PDMS/PDMS-magnetite-based composites was shown to have an optimum efficiency of ~31.8%. The implications of the results are discussed for potential applications of PDMS nanocomposites in implantable biomedical devices.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Dimetilpolisiloxanos/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Nanocompostos/química , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Óxido Ferroso-Férrico , Temperatura Alta , Humanos , Lasers , Próteses e Implantes , Propriedades de Superfície , Titânio/química
15.
J Biomed Mater Res B Appl Biomater ; 109(12): 2041-2056, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33960623

RESUMO

This paper presents in vitro studies of the sustained release of Annona muricata leaf extracts (AME) from hybrid electrospun fibers for breast cancer treatment. Electrospun hybrid scaffolds were fabricated from crude AME extracts, poly(lactic-co-glycolic acid)/gelatin (PLGA/Ge) and pluronic F127. The physicochemical properties of the AME extract and scaffolds were studied. The antiproliferative effects of the scaffolds were also assessed on breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic breast (MCF10A) cell lines. Scanning electron microscope micrographs revealed a random network of micro- and submicron fibers. In vitro drug release profiles, governed by quasi-Fickian diffusion at pH 7.4 and non-Fickian super case II at pH 6.7, showed initial burst AME release from the PLGA/Ge-AME and PLGA/Ge-F127/AME fibers at pH 7.4, and burst release from PLGA/Ge-F127/AME (not observed from PLGA/Ge-AME) at pH 6.7. Then, a slower, sustained release of the remaining AME from the fibers, attributed to the onset of degradation of the PLGA/Ge backbone, was observed for the next 72 hr. The cumulative release of AME was 89.33 ± 0.73% (PLGA/Ge-AME) and 51.17 ± 7.96% (PLGA/Ge-F127/AME) at pH 7.4, and 9.27 ± 2.3% and 73.5 ± 4.5%, respectively, at pH 6.7. Pluronic F127 addition increased the drug loading capacity and prolonged the sustained AME release from the fibers. The released AME significantly inhibited the in vitro growth of the breast cancer cells more than the non-tumorigenic cells, due to the induction of apoptosis, providing evidence for using pluronic F127-containing electrospun fibers for sustained and localized AME delivery to breast cancer cells.


Assuntos
Annona , Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Liberação Controlada de Fármacos , Feminino , Humanos , Poloxâmero/química , Poloxâmero/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química
16.
J Mech Behav Biomed Mater ; 119: 104505, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33857875

RESUMO

This paper presents the results of a study of the actin cytoskeletal structures and the statistical variations in the actin fluorescence intensities and viscoelastic properties of non-tumorigenic breast cells and triple-negative breast cancer cells at different stages of tumor progression. The variation in the actin content of the cell cytoskeletal structures is shown to be consistent with the viscoelastic properties of the cell as it progresses from non-tumorigenic to more metastatic states. The corresponding viscoelastic properties of the nuclei and the cytoplasm (Young's moduli, viscosities, and relaxation times) of the cells are also measured using Digital Image Correlation (DIC) and shear assay techniques. These properties are shown to exhibit statistical variations that are well characterized by normal distributions. The changes in the mean properties of individual cancer cells are tested using Fisher pairwise comparisons and the analysis of variance (ANOVA). The implications of the results are then discussed for the development of shear assay techniques and mechanical biomarkers for the detection of triple-negative breast cancer at different stages of tumor progression.


Assuntos
Actinas , Neoplasias de Mama Triplo Negativas , Citoesqueleto , Módulo de Elasticidade , Humanos , Viscosidade
17.
J Biomed Mater Res A ; 108(12): 2421-2434, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32362069

RESUMO

This article presents the results of the combined effects of RGD (arginine-glycine-aspartate) functionalization and mechanical stimulation on osteogenesis that could lead to the development of implantable robust tissue-engineered mineralized constructs. Porous polycaprolactone/hydroxyapatite (PCL/HA) scaffolds are functionalized with RGD-C (arginine-glycine-aspartate-cysteine) peptide. The effects of RGD functionalization are then explored on human fetal osteoblast cell adhesion, proliferation, osteogenic differentiation (alkaline phosphatase activity), extracellular matrix (ECM) production, and mineralization over 28 days. The effects of RGD functionalization followed by mechanical stimulation with a cyclic fluid shear stress of 3.93 mPa in a perfusion bioreactor are also elucidated. The tensile properties (Young's moduli and ultimate tensile strengths) of the cell-laden scaffolds are measured at different stages of cell culture to understand how the mechanical properties of the tissue-engineered structures evolve. RGD functionalization is shown to promote initial cell adhesion, proliferation, alkaline phosphatase (ALP) activity, and ECM production. However, it does not significantly affect mineralization and tensile properties. Mechanical stimulation after RGD functionalization is shown to further improve the ALP activity, ECM production, mineralization, and tensile properties, but not cell proliferation. The results suggest that combined RGD functionalization and mechanical stimulation of cell-laden PCL/HA scaffolds can be used to accelerate the regeneration of robust bioengineered bone structures.


Assuntos
Durapatita/química , Oligopeptídeos/química , Osteoblastos/metabolismo , Osteogênese , Poliésteres/química , Alicerces Teciduais/química , Linhagem Celular , Humanos , Estresse Mecânico
18.
J Mech Behav Biomed Mater ; 108: 103750, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32310105

RESUMO

This paper presents the results of theoretical and experimental studies of the compressive deformation of bamboo (Bambusa Vulgaris-Schrad) in the middle section. The deformation mechanisms are elucidated via in-situ observations of deformation in specimens oriented for loading in directions that are either longitudinal or transverse. Compressive deformation is shown to result in progressive micro-buckling and kink band formation. The onset of micro-buckling is also shown to be well predicted by an Euler buckling model. The critical loads for failure in the transverse orientation are also shown to be consistent with the conditions for shear yielding in the plies with fibers that are oriented in an orthogonal direction to the loading axis.


Assuntos
Bambusa , Força Compressiva
19.
Acta Biomater ; 97: 535-543, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310853

RESUMO

Turtle shells comprising of cortical and trabecular bones exhibit intriguing mechanical properties. In this work, compression tests were performed using specimens made from the carapace of Kinixys erosa turtle. A combination of imaging techniques and mechanical testing were employed to examine the responses of hierarchical microstructures of turtle shell under compression. Finite element models produced from microCT-scanned microstructures and analytical foam structure models were then used to elucidate local responses of trabecular bones deformed under compression. The results reveal the contributions from micro-strut bending and stress concentrations to the fractural mechanisms of trabecular bone structures. The porous structures of turtle shells could be an excellent prototype for the bioinspired design of deformation-resistant structures. STATEMENT OF SIGNIFICANCE: In this study, a combination of analytical, computational models and experiments is used to study the underlying mechanisms that contribute to the compressive deformation of a Kinixys erosa turtle shell between the nano-, micro- and macro-scales. The proposed work shows that the turtle shell structures can be analyzed as sandwich structures that have the capacity to concentrate deformation and stresses within the trabecular bones, which enables significant energy absorption during compressive deformation. Then, the trends in the deformation characteristics and the strengths of the trabecular bone segments are well predicted by the four-strut model, which captures the effects of variations in strut length, thickness and orientation that are related to microstructural uncertainties of the turtle shells. The above results also suggest that the model may be used to guide the bioinspired design of sandwich porous structures that mimic the properties of the cortical and trabecular bone segments of turtle shells under a range of loading conditions.


Assuntos
Exoesqueleto , Estresse Mecânico , Tartarugas/anatomia & histologia , Microtomografia por Raio-X , Exoesqueleto/química , Exoesqueleto/diagnóstico por imagem , Animais , Porosidade
20.
J Mech Behav Biomed Mater ; 86: 1-13, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29913305

RESUMO

An improved understanding of the evolution of cell structure and viscoelasticity with cancer malignancy could enable the development of a new generation of biomarkers and methods for cancer diagnosis. Hence, in this study, we present the viscoelastic properties (moduli and viscosities) and the actin cytoskeletal structures of triple negative breast cancer (TNBC) cells with different metastatic potential. These include: MCF-10A normal breast cells (studied as a control); MDA-MB-468 cells (less metastatic TNBC cells), and MDA-MB-231 cells (highly metastatic TNBC cells). A combination of shear assay and digital imaging correlation (DIC) techniques is used to measure the local viscoelastic properties of live breast cells subjected to constant shear stress. The local moduli and viscosities of the nuclei and cytoplasm are characterized using a generalized Maxwell model, which is used to determine the time-dependent creep responses of cells. The nuclei are shown to be stiffer and more viscous than the cytoplasms of the normal breast cells and TNBC cells. The MCF-10A normal breast cells are found to be twice as stiff as the less metastatic MDA-MB-468 breast cancer cells and over ten times stiffer than the highly metastatic MDA-MB-231 breast cancer cells. Similar trends are also observed in the viscosities of the nuclei and the cytoplasms. The measured differences in cell viscoelastic properties are also associated with significant changes in the cell cytoskeletal structure, which is studied using confocal fluorescence microscopy. This reveals significant differences in the levels of actin expression and organization in TNBC cells as they become highly metastatic. Our results suggest that the shear assay measurements of cell viscoelastic properties may be used as effective biomarkers for TNBC diagnosis and screening.


Assuntos
Citoesqueleto de Actina/metabolismo , Elasticidade , Neoplasias de Mama Triplo Negativas/patologia , Fenômenos Biomecânicos , Linhagem Celular Tumoral , Humanos , Metástase Neoplásica , Viscosidade
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