Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer

Ermis, Menekşe; Falcone, Natashya; Barros, Natan Roberto de; Mecwan, Marvin; Haghniaz, Reihaneh; Choroomi, Auveen; Monirizad, Mahsa; Lee, Yeji; Song, JiHyeon; Cho, Hyun‐Jong; Zhu, Yangzhi; Dokmeci, Mehmet R.; Khademhosseini, Ali; Lee, Junmin; Kim, Hanjun

doi:10.1016/j.bioactmat.2023.02.005

Cited by 16 publications

(10 citation statements)

References 65 publications

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“…34 Previous researches have revealed that the mechanical properties of normal pancreatic tissue range from 1 to 4 kPa, while those of tissues with excessive collagen deposition reach about 40 kPa. 35 In our research, matrix stiffness matches the mechanical properties of healthy and pancreatic carcinoma tissue through adjusting the GelMA concentration and UV exposure time (Fig. 1A).…”

Section: Resultssupporting

confidence: 61%

Matrix stiffness triggers chemoresistance through elevated autophagy in pancreatic ductal adenocarcinoma

Pan,

Zhu,

Gong

et al. 2023

Biomater. Sci.

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Section: Resultssupporting

confidence: 61%

Matrix stiffness triggers chemoresistance through elevated autophagy in pancreatic ductal adenocarcinoma

Pan,

Zhu,

Gong

et al. 2023

Biomater. Sci.

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“…3 A). The mostly commonly used scaffold is hydrogels [ 38 ]. To mimic the extracellular matrix for better protection of 3D cell spheres, Tayalia et al created an affordable semi-synthetic cryogel matrix system [ 39 ] derived from polyethylene glycol diacrylate (PEGDA) and gelatin methacryloyl (GELMA).…”

Section: Models For Evaluation Of the Degree Of Tumor Penetrationmentioning

confidence: 99%

Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives

Shen,

Pan,

Gong

et al. 2024

Bioactive Materials

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“…In a recent work by our group, hybrid methacrylate hyaluronic acid/GelMA (HAMA/GelMA) hydrogels were evaluated regarding their ability to model desmoplastic PDAC [89]. In the study, spheroids composed of co-culture of PDAC cells and fibroblasts were cultured within HAMA/GelMA hydrogels mimicking different levels of tissue stiffness, from healthy pancreas tissue to hyper desmoplastic PDAC.…”

Section: Gene and Protein Expression Analysis Of 3d Bioprinting Pancr...mentioning

confidence: 99%

Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling

et al. 2023

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Three-dimensional (3D) in vitro tumor models that can capture the pathophysiology of human tumors are essential for cancer biology and drug development. However, simulating the tumor microenvironment is still challenging because it consists of a heterogeneous mixture of various cellular components and biological factors. In this regard, current extracellular matrix (ECM)-mimicking hydrogels used in tumor tissue engineering lack physical interactions that can keep biological factors released by encapsulated cells within the hydrogel and improve paracrine interactions. Here, we developed a nanoengineered ion-covalent cross-linkable bioink to construct 3D bioprinted organotypic tumor models. The bioink was designed to implement the tumor ECM by creating an interpenetrating network composed of gelatin methacryloyl (GelMA), a light cross-linkable polymer, and synthetic nanosilicate (Laponite) that exhibits a unique ionic charge to improve retention of biological factors released by the encapsulated cells and assist in paracrine signals. The physical properties related to printability were evaluated to analyze the effect of Laponite hydrogel on bioink. Low GelMA (5%) with high Laponite (2.5-3.5%) composite hydrogels and high GelMA (10%) with low Laponite (1.0-2.0%) composite hydrogels showed acceptable mechanical properties for 3D printing. However, a low GelMA composite hydrogel with a high Laponite content could not provide acceptable cell viability. Fluorescent cell labeling studies showed that as the proportion of Laponite increased, the cells became more aggregated to form larger 3D tumor structures. RT-qPCR and western blot experiments showed that an increase in the Laponite ratio induces upregulation of growth factor and tissue remodeling-related genes and proteins in tumor cells. In contrast, cell cycle and proliferation-related genes were downregulated. On the other hand, concerning fibroblasts, the increase in the Laponite ratio indicated an overall upregulation of the mesenchymal phenotype-related genes and proteins. Our study may provide a rationale for using Laponite-based hydrogels in 3D cancer modeling.

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Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer

Cited by 16 publications

References 65 publications

Matrix stiffness triggers chemoresistance through elevated autophagy in pancreatic ductal adenocarcinoma

Matrix stiffness triggers chemoresistance through elevated autophagy in pancreatic ductal adenocarcinoma

Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives

Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling

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