Probing vocal fold fibroblast response to hyaluronan in 3D contexts

Muñoz-Pinto, Dany J.; Jimenez-Vergara, Andrea Carolina; Gelves, L. Marcela; McMahon, Rebecca E.; Guiza-Arguello, Viviana; Hahn, Mariah S.

doi:10.1002/bit.22436

Cited by 25 publications

(51 citation statements)

References 60 publications

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“…Measures of DNA were used to assess viability, as they are considered standard indicators of net cell proliferation and death within hydrogel networks. 60 Chondrocyte and macrophage DNA measures at the endpoint were *73% of their initial values at the time of encapsulation ( Supplementary Fig. S3), consistent with PEG hydrogel literature.…”

Section: D System To Study Effects Of Osteoarthritic Inflammationsupporting

confidence: 85%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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Section: D System To Study Effects Of Osteoarthritic Inflammationsupporting

confidence: 85%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

Self Cite

View full text Add to dashboard Cite

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“…63 For example, elastin synthesis by vocal fold fibroblasts was found to be inversely related to the molecular weight of HA included in HA-polyacrylamide gels. 32 …”

Section: Base Materials For the Construction Of Hydrogels For Fibroblmentioning

confidence: 99%

“…The molecular weight of the HA included in the gel was observed to affect fibroblast behavior, with intermediate molecular weight HA inducing activation. 32 In addition to cell encapsulation, other methods of achieving 3D-like cell culture have been employed, including inducing fibroblast migration into the hydrogel 81 and patterning hydrogels with pores into which fibroblasts are seeded. 120 In order to conduct 3D studies using encapsulation and migration techniques, cellular remodeling of the hydrogel must be possible.…”

Section: Increasing Dimensionality Towards a Better Understanding Of mentioning

confidence: 99%

Hydrogel scaffolds asin vitromodels to study fibroblast activation in wound healing and disease

2014

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Wound healing results from complex signaling between cells and their environment in response to injury. Fibroblasts residing within the extracellular matrix (ECM) of various connective tissues are critical for matrix synthesis and repair. Upon injury or chronic insult, these cells activate into wound-healing cells, called myofibroblasts, and repair the damaged tissue through enzyme and protein secretion. However, misregulation and persistence of myofibroblasts can lead to uncontrolled accumulation of matrix proteins, tissue stiffening, and ultimately disease. Extracellular cues are important regulators of fibroblast activation and have been implicated in their persistence. Hydrogel-based culture models have emerged as useful tools to examine fibroblast response to ECM cues presented during these complex processes. In this Mini-Review, we will provide an overview of these model systems, which are built upon naturally-derived or synthetic materials, and mimic relevant biophysical and biochemical properties of the native ECM with different levels of control. Additionally, we will discuss the application of these hydrogel-based systems for the examination of fibroblast function and fate, including adhesion, migration, and activation, as well as approaches for mimicking both static and temporal aspects of extracellular environments. Specifically, we will highlight hydrogels that have been used to investigate the effects of matrix rigidity, protein binding, and cytokine signaling on fibroblast activation. Last, we will describe future directions for the design of hydrogels to develop improved synthetic models that mimic the complex extracellular environment.

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“…The number of VICs in suspension was assessed via Quant-iT PicoGreen dsDNA Kit (Life Technologies) per manufacturer’s protocol using a conversion factor of 5.6 pg DNA/cell 20,40,58 . The percentage of cell adhesion was calculated as the measured cell density divided by the seeding density.…”

Section: Methodsmentioning

confidence: 99%

Adhesive Peptide Sequences Regulate Valve Interstitial Cell Adhesion, Phenotype and Extracellular Matrix Deposition

Grande‐Allen

West

2016

Cel. Mol. Bioeng.

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Knowledge of how extracellular matrix (ECM) binding impacts valve interstitial cells (VICs) is critical not only to better understanding the etiology of valvular diseases but also to constructing living valve substitutes that can grow and remodel. Use of ECM-mimicking adhesive peptides with specific affinity to different receptors provides insights into adhesion-mediated cell signaling and downstream outcomes. Expression of adhesion receptors by VICs was assessed by flow cytometry and used to guide the choice of peptides studied. The peptide RGDS with affinity to multiple integrin receptors, and specific receptor-targeting peptides DGEA (integrin α 2 β 1 ), YIGSR (67kDa laminin/elastin receptor; 67LR), and VAPG (67LR) were incorporated into hydrogels to investigate their effects on VICs. DGEA, YIGSR, and VAPG alone were insufficient to induce stable VIC adhesion. As a result, these peptides were studied in combination with 1 mM RGDS. For VICs cultured on two-dimensional hydrogel surfaces, YIGSR and VAPG down-regulated the expression of smooth muscle α-actin (myofibroblast activation marker); DGEA promoted VIC adhesion and VIC-mediated ECM deposition and inhibited the activity of alkaline phosphatase (osteogenic differentiation marker). Further, YIGSR and DGEA in combination promoted ECM deposition while inhibiting both myofibroblastic and osteogenic differentiation. However, VICs behaved differently to adhesive ligands when cultured within three-dimensional hydrogels, with most VICs assuming a healthy, quiescent phenotype under all peptide conditions tested. DGEA promoted ECM deposition by VICs within hydrogels. Overall, we demonstrate that the presentation of defined peptides targeting specific adhesion receptors can be used to regulate VIC adhesion, phenotype and ECM synthesis.

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Probing vocal fold fibroblast response to hyaluronan in 3D contexts

Cited by 25 publications

References 60 publications

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Hydrogel scaffolds asin vitromodels to study fibroblast activation in wound healing and disease

Adhesive Peptide Sequences Regulate Valve Interstitial Cell Adhesion, Phenotype and Extracellular Matrix Deposition

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