Embedded Bioprinting of Tumor-Scale Pancreatic Cancer-Stroma 3D Models for Preclinical Drug Screening DOI
Maria V. Monteiro, Marta Rocha, Mariana T. Carvalho

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(42), P. 56718 - 56729

Published: Oct. 10, 2024

The establishment of organotypic preclinical models that accurately resemble the native tumor microenvironment at an anatomic human scale is highly desirable to level up in vitro platforms potential for screening candidate therapies. bioengineering anatomic-scaled three-dimensional (3D) emulate while recapitulating their cellular and matrix components remains, however, be fully realized. In this focus, herein, we leveraged embedded 3D bioprinting biofabricating pancreatic ductal adenocarcinoma (PDAC) combining gelatin-methacryloyl hyaluronic acid methacrylate extracellular (ECM)-mimetic biomaterials with cancer cells cancer-associated fibroblasts generate capable emulating size (∼6 mm) stromal elements. By using a viscoelastic continuous polymeric supporting bath, tumor-scale were rapidly generated (∼50 constructs/h) easily recovered following in-bath visible light photocrosslinking. As proof-of-concept, tissue-scale constructs displaying physiomimetic designs biofabricated. These also encompass incorporation compartment better PDAC (TME) its stratified spatial organization. Cell-laden tumor-size remained viable 14 days responsive Gemcitabine dose-dependent mode. Cancer-stroma exhibited increased drug resistance compared monotypic counterparts, highlighting key role chemotherapeutic resistance. Overall, report first time freeform biofabrication exhibiting scale, different structural complexities, engineered cancer-stromal compartments, being valuable therapeutics.

Language: Английский

Embedded Bioprinting of Tumor-Scale Pancreatic Cancer-Stroma 3D Models for Preclinical Drug Screening DOI
Maria V. Monteiro, Marta Rocha, Mariana T. Carvalho

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(42), P. 56718 - 56729

Published: Oct. 10, 2024

The establishment of organotypic preclinical models that accurately resemble the native tumor microenvironment at an anatomic human scale is highly desirable to level up in vitro platforms potential for screening candidate therapies. bioengineering anatomic-scaled three-dimensional (3D) emulate while recapitulating their cellular and matrix components remains, however, be fully realized. In this focus, herein, we leveraged embedded 3D bioprinting biofabricating pancreatic ductal adenocarcinoma (PDAC) combining gelatin-methacryloyl hyaluronic acid methacrylate extracellular (ECM)-mimetic biomaterials with cancer cells cancer-associated fibroblasts generate capable emulating size (∼6 mm) stromal elements. By using a viscoelastic continuous polymeric supporting bath, tumor-scale were rapidly generated (∼50 constructs/h) easily recovered following in-bath visible light photocrosslinking. As proof-of-concept, tissue-scale constructs displaying physiomimetic designs biofabricated. These also encompass incorporation compartment better PDAC (TME) its stratified spatial organization. Cell-laden tumor-size remained viable 14 days responsive Gemcitabine dose-dependent mode. Cancer-stroma exhibited increased drug resistance compared monotypic counterparts, highlighting key role chemotherapeutic resistance. Overall, report first time freeform biofabrication exhibiting scale, different structural complexities, engineered cancer-stromal compartments, being valuable therapeutics.

Language: Английский

Citations

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