Development of a mechanically matched silk scaffolded 3D clear cell renal cell carcinoma model

Abbott, Alycia; Bond, Kyle H.; Chiba, Takuto; Sims‐Lucas, Sunder; Oxburgh, Leif; Coburn, Jeannine M.

doi:10.1016/j.msec.2021.112141

Cited by 8 publications

(12 citation statements)

References 67 publications

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“…1 (I)), we found that expression levels of almost all of the genes of cell cycle-related pathways were lower in the CSC and 3D models than in 2D models. This finding is similar to that in a previous study on clear cell renal cell carcinoma [ 46 ]. As for metabolism-related pathways, 3D models showed weak anabolism and strong catabolism, and the CSC model was almost the same as the 3D model, except for glycosaminoglycan biosynthesis, confirming that spatial structure has a great influence on cell metabolism.…”

Section: Discussionsupporting

confidence: 93%

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

Lin

Yang

Yuan

et al. 2022

Bioactive Materials

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Section: Discussionsupporting

confidence: 93%

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

Lin

Yang

Yuan

et al. 2022

Bioactive Materials

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“…14,17,20,24 Scaffolds have been produced through rate-controlled or nonrate-controlled freezing techniques followed by lyophilization. 14,20,24,57,58 Limitations were associated with current-ratecontrolled freezing lyophilization protocols wherein ≥9% silk (w/v) solutions failed to exhibit adequate water removal during primary drying and boiling during the secondary drying phase. To address these issues, new lyophilization protocols capable of producing scaffolds were developed from 9% and 12% silk solutions, and the resultant scaffolds were characterized.…”

Section: Discussionmentioning

confidence: 99%

Influence of lyophilization primary drying time and temperature on porous silk scaffold fabrication for biomedical applications

Abbott

Gravina

Vandadi

et al. 2022

J Biomedical Materials Res

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Lyophilization of protein solutions, such as silk fibroin (silk), produces porous scaffolds useful for tissue engineering (TE). The impact of modifying lyophilization primary drying parameters on scaffold properties has not yet been explored previously.In this work, changes to primary drying duration and temperature were investigated using 3%, 6%, 9%, and 12% (w/v) silk solutions, via protocols labeled as Long Hold, Slow Ramp, and Standard. The 9% and 12% scaffolds were not successfully fabricated using the Standard protocol, while the Long Hold and Slow Ramp protocols resulted in scaffolds from all silk solution concentrations. Scaffolds fabricated using the Long Hold protocol had higher Young's moduli, smaller pore Feret diameters, and faster degradation. To investigate the utility of the different lyophilized scaffolds for in vitro cell culturing, the HepaRG liver cell line was cultured in the 3% to 12% scaffolds fabricated using the Long Hold protocol. The HepaRG cells grown in 3% scaffolds initially had greater lipid accumulation and metabolic activity than the other groups, although these differences were no longer apparent by Day 28. The deoxyribonucleic acid content of the HepaRG cells grown in 3% scaffold group was also initially significantly higher than the other groups. Significant differences in gene expression by 9% scaffolded HepaRG cells (CK19, HNFα) were seen on Day 14 while significant differences by 12% scaffolded HepaRG cells (ALB, APOA4) were seen on Day 28. Overall, modifying the primary drying parameters and silk concentration resulted in lyophilized scaffolds with tunable properties useful for TE applications.

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“…In many tumors, the alteration in ECM content results in a more rigid matrix that promotes malignancy [ 83 ], but in ccRCC we have found that this is not the case: modulus testing of tumors versus adjacent healthy cortex revealed a lower modulus in tumors [ 84 ]. This suggests that the ECM profile of ccRCCs defined in our analysis reduces tissue rigidity in comparison with the healthy surrounding tissue, perhaps contributing to the indolent progression of ccRCC tumors, which genetic analysis has revealed generally develop over decades [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

The Extracellular Matrix Environment of Clear Cell Renal Cell Carcinoma Determines Cancer Associated Fibroblast Growth

Bond

Chiba

Wynne

et al. 2021

Cancers

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Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and is often caused by mutations in the oxygen-sensing machinery of kidney epithelial cells. Due to its pseudo-hypoxic state, ccRCC recruits extensive vasculature and other stromal components. Conventional cell culture methods provide poor representation of stromal cell types in primary cultures of ccRCC, and we hypothesized that mimicking the extracellular environment of the tumor would promote growth of both tumor and stromal cells. We employed proteomics to identify the components of ccRCC extracellular matrix (ECM) and found that in contrast to healthy kidney cortex, laminin, collagen IV, and entactin/nidogen are minor contributors. Instead, the ccRCC ECM is composed largely of collagen VI, fibronectin, and tenascin C. Analysis of single cell expression data indicates that cancer-associated fibroblasts are a major source of tumor ECM production. Tumor cells as well as stromal cells bind efficiently to a nine-component ECM blend characteristic of ccRCC. Primary patient-derived tumor cells bind the nine-component blend efficiently, allowing to us to establish mixed primary cultures of tumor cells and stromal cells. These miniature patient-specific replicas are conducive to microscopy and can be used to analyze interactions between cells in a model tumor microenvironment.

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Development of a mechanically matched silk scaffolded 3D clear cell renal cell carcinoma model

Cited by 8 publications

References 67 publications

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

Multi-omics analysis based on 3D-bioprinted models innovates therapeutic target discovery of osteosarcoma

Influence of lyophilization primary drying time and temperature on porous silk scaffold fabrication for biomedical applications

The Extracellular Matrix Environment of Clear Cell Renal Cell Carcinoma Determines Cancer Associated Fibroblast Growth

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