Decellularized Extracellular Matrix Composite Hydrogel Bioinks for the Development of 3D Bioprinted Head and Neck in Vitro Tumor Models
| Autor: | Joseph M. Kinsella, Allen J. Ehrlicher, Jose G. Munguia-Lopez, Jiang Tao, Luc Mongeau, Jacqueline Kort-Mascort, Guangyu Bao, Salvador Flores-Torres, Simon D. Tran, Osama A Elkashty |
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| Rok vydání: | 2021 |
| Předmět: |
Biomedical Engineering
02 engineering and technology Biomaterials Extracellular matrix Mice 03 medical and health sciences Tissue engineering In vivo medicine Animals 030304 developmental biology 0303 health sciences Tumor microenvironment Decellularization Tissue Engineering Tissue Scaffolds Chemistry Bioprinting Hydrogels 021001 nanoscience & nanotechnology medicine.disease Head and neck squamous-cell carcinoma Extracellular Matrix Printing Three-Dimensional Self-healing hydrogels Biophysics 0210 nano-technology Biofabrication |
| Zdroj: | ACS Biomaterials Science & Engineering. 7:5288-5300 |
| ISSN: | 2373-9878 |
| Popis: | Reinforced extracellular matrix (ECM)-based hydrogels recapitulate several mechanical and biochemical features found in the tumor microenvironment (TME) in vivo. While these gels retain several critical structural and bioactive molecules that promote cell-matrix interactivity, their mechanical properties tend toward the viscous regime limiting their ability to retain ordered structural characteristics when considered as architectured scaffolds. To overcome this limitation characteristic of pure ECM hydrogels, we present a composite material containing alginate, a seaweed-derived polysaccharide, and gelatin, denatured collagen, as rheological modifiers which impart mechanical integrity to the biologically active decellularized ECM (dECM). After an optimization process, the reinforced gel proposed is mechanically stable and bioprintable and has a stiffness within the expected physiological values. Our hydrogel's elastic modulus has no significant difference when compared to tumors induced in preclinical xenograft head and neck squamous cell carcinoma (HNSCC) mouse models. The bioprinted cell-laden model is highly reproducible and allows proliferation and reorganization of HNSCC cells while maintaining cell viability above 90% for periods of nearly 3 weeks. Cells encapsulated in our bioink produce spheroids of at least 3000 μm2 of cross-sectional area by day 15 of culture and are positive for cytokeratin in immunofluorescence quantification, a common marker of HNSCC model validation in 2D and 3D models. We use this in vitro model system to evaluate the standard-of-care small molecule therapeutics used to treat HNSCC clinically and report a 4-fold increase in the IC50 of cisplatin and an 80-fold increase for 5-fluorouracil compared to monolayer cultures. Our work suggests that fabricating in vitro models using reinforced dECM provides a physiologically relevant system to evaluate malignant neoplastic phenomena in vitro due to the physical and biological features replicated from the source tissue microenvironment. |
| Databáze: | OpenAIRE |
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