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Decellularized Extracellular Matrix Composite Hydrogel Bioinks for the Development of 3D Bioprinted Head and Neck in Vitro Tumor Models
Jacqueline Kort-Mascort, Guangyu Bao, Osama Elkashty, Salvador Flores-Torres, Jose G. Munguia-Lopez, Tao Jiang, Allen J. Ehrlicher, Luc Mongeau, Simon D. Tran, and Joseph M. Kinsella
ACS Biomater. Sci. Eng., online October 18, 2021
The common methods utilizing in vitro monolayer cell culture systems and preclinical in vivo small animal tumor xenografts can be deficient or introduce biological cues that are not present in native human tumors. To address this, the authors have sought to develop bioprintable materials for encapsulating tumor cells that have acceptable printability, cell proliferation, spheroid formation, and stiffness.
They prepared the bioink by decellularizing porcine tongue tissue (dECMT) and incorporating sodium alginate and gelatin at controlled weight percentages as rheological modifiers. LC-MS/MS of the dECMT found the proteins included different types of collagens, laminin, and glycosaminoglycans with collagens the most abundant structural proteins, accounting for more than 90% of the total ECM protein.
They characterized the mechanical and biochemical properties of the composite materials, and used them to encapsulate human head and neck squamous cell carcinoma cells. The bioprinted 3D structures allowed the cancer cells to develop into tumor spheroids over 19 days while maintaining high cell viability and supporting proliferation.
Dose-response experiments revealed increased IC50 values for both cisplatin and 5-fluorouracil cultured in these 3D models when compared to 2D conditions. The decrease in sensitivity observed in 3D cultures can be attributed to the non-physiological conditions that 2D cultures offer.
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