The Effect of Biomolecular Gradients on Mesenchymal Stem Cell Chondrogenesis under Shear Stress

Rivera, Alexander L.; Baskaran, Harihara

doi:10.3390/mi6030330

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…Furthermore, in native cartilage the oriented structure plays a crucial role in supporting load by tissue. In other words, aligned cells produce aligned ECM fibers and this increases the mechanical properties of the tissue constructs . The higher metabolic activity of chondrocytes in the indirect presence of DC‐ECM nanoparticles can be to a certain extent attributed to the presence of such oriented cellular morphology.…”

Section: Discussionmentioning

confidence: 99%

Chondrogenic response in presence of cartilage extracellular matrix nanoparticles

Zahiri

Masaeli

Poorazizi

et al. 2018

J Biomedical Materials Res

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Current studies based on regenerative medicine suggest, decellularized extracellular matrix (DC-ECM) components can regulate cell phenotype. In this regard, it is believed, presence of cartilage extracellular matrix particles in culture condition could produce physical and biochemical supportive cues for chondrogenesis. In this study, DC-ECM nanoparticles with average size of 61.5± 22.4 nm were produced by decellularization and mechanical processing. Homogenous distribution and nanoscale size of yield particles were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) microscopy imaging. Chemical structure preservation of cartilage ECM after decellularization was also confirmed by typical Fourier transform infrared (FTIR) spectrum mapping. The influence these nanoparticles on chondrogenic response of chondrocyte cells was investigated by direct and indirect addition of nanoparticles to culture medium. A clinical devitalized cartilage powder (DV-ECM) was also used as a positive control. Totally, MTS results showed that direct and indirect presence of both DC-ECM and DV-ECM particles in culture medium enhanced cellular metabolic activity except on day one of culture. Furthermore, on day 21, SOX9 and COL2 expression of cultured chondrocytes in the medium containing DC-ECM nanoparticles were up-regulated in comparison to negative control, which was further confirmed by presence more frequent number of larger size lacunae in micromass spheroids. Our findings support the use of ECM nanoparticles as condition supplement in culture medium and injectable biomaterials, especially for cell-based therapies for cartilage regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2463-2471, 2018.

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Section: Discussionmentioning

confidence: 99%

Chondrogenic response in presence of cartilage extracellular matrix nanoparticles

Zahiri

Masaeli

Poorazizi

et al. 2018

J Biomedical Materials Res

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“…The biggest disadvantage of such culture systems is that it does not fully replicate the microenvironment experienced in vivo where cells grow within a complex three-dimensional (3D) matrix and, as the 3D structure impacts biological processes from the molecular level (i.e. gene and protein synthesis, and biomolecular gradients) [ 3 ] to the proliferation, differentiation and apoptotic nature of the cells, consideration of this key factor must be sought [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Influence of surface geometry on the culture of human cell lines: A comparative study using flat, round-bottom and v-shaped 96 well plates

et al. 2017

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In vitro cell based models have been invaluable tools for studying cell behaviour and for investigating drug disposition, toxicity and potential adverse effects of administered drugs. Within this drug discovery pipeline, the ability to assess and prioritise candidate compounds as soon as possible offers a distinct advantage. However, the ability to apply this approach to a cell culture study is limited by the need to provide an accurate, in vitro-like, microenvironment in conjunction with a low cost and high-throughput screening (HTS) methodology. Although the geometry and/or alignment of cells has been reported to have a profound influence on cell growth and differentiation, only a handful of studies have directly compared the growth of a single cell line on different shaped multiwell plates the most commonly used substrate for HTS, in vitro, studies. Herein, the impact of various surface geometries (flat, round and v-shaped 96 well plates), as well as fixed volume growth media and fixed growth surface area have been investigated on the characteristics of three commonly used human cell lines in biopharmaceutical research and development, namely ARPE-19 (retinal epithelial), A549 (alveolar epithelial) and Malme-3M (dermal fibroblastic) cells. The effect of the surface curvature on cells was characterised using a combination of a metabolic activity assay (CellTiter AQ/MTS), LDH release profiles (CytoTox ONE) and absolute cell counts (Guava ViaCount), respectively. In addition, cell differentiation and expression of specific marker proteins were determined using flow cytometry. These in vitro results confirmed that surface topography had a significant effect (p < 0.05) on cell activity and morphology. However, although specific marker proteins were expressed on day 1 and 5 of the experiment, no significant differences were seen between the different plate geometries (p < 0.05) at the later time point. Accordingly, these results highlight the impact of substrate geometry on the culture of a cell line and the influence it has on the cells’ correct growth and differentiation characteristics. As such, these results provide important implications in many aspects of cell biology the development of a HTS, in vitro, cell based systems to further investigate different aspects of toxicity testing and drug delivery.

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“…In this scenario, microfluidics has major advantages compared to conventional 2D culture due to the possibility of replicating some aspects of the in vivo 3D environment in terms of both biochemical and physical stimuli. In this context, Rivera and Baskaran [ 17 ] have developed a microfluidic device to investigate simultaneously the influence of shear stress and biomolecular gradients on BMSC alignment and chondrogenesis. The 3-week exposure to TGF- β 1 gradients via fluid flow enhanced the formation of chondrogenic aggregates with an increased cell elongation in flow direction when compared to a constant TGF- β 1 concentration.…”

Section: Microfluidics and Bioprinting To Trigger The Translation mentioning

confidence: 99%

Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

Lopa

Mondadori

Mainardi

et al. 2018

Stem Cells International

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Cartilage defects can impair the most elementary daily activities and, if not properly treated, can lead to the complete loss of articular function. The limitations of standard treatments for cartilage repair have triggered the development of stem cell-based therapies. In this scenario, the development of efficient cell differentiation protocols and the design of proper biomaterial-based supports to deliver cells to the injury site need to be addressed through basic and applied research to fully exploit the potential of stem cells. Here, we discuss the use of microfluidics and bioprinting approaches for the translation of stem cell-based therapy for cartilage repair in clinics. In particular, we will focus on the optimization of hydrogel-based materials to mimic the articular cartilage triggered by their use as bioinks in 3D bioprinting applications, on the screening of biochemical and biophysical factors through microfluidic devices to enhance stem cell chondrogenesis, and on the use of microfluidic technology to generate implantable constructs with a complex geometry. Finally, we will describe some new bioprinting applications that pave the way to the clinical use of stem cell-based therapies, such as scaffold-free bioprinting and the development of a 3D handheld device for the in situ repair of cartilage defects.

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The Effect of Biomolecular Gradients on Mesenchymal Stem Cell Chondrogenesis under Shear Stress

Cited by 8 publications

References 42 publications

Chondrogenic response in presence of cartilage extracellular matrix nanoparticles

Chondrogenic response in presence of cartilage extracellular matrix nanoparticles

Influence of surface geometry on the culture of human cell lines: A comparative study using flat, round-bottom and v-shaped 96 well plates

Translational Application of Microfluidics and Bioprinting for Stem Cell-Based Cartilage Repair

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