Alginate-gelatin bioink for bioprinting of hela spheroids in alginate-gelatin hexagon shaped scaffolds
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Alginate‑gelatin bioink for bioprinting of hela spheroids in alginate‑gelatin hexagon shaped scaffolds Sheril Amira Othman1 · Chin Fhong Soon1 · Nyuk Ling Ma2 · Kian Sek Tee1 · Gim Pao Lim1 · Marlia Morsin2 · Mohd Khairul Ahmad1 · Alyaa Idrees Abdulmaged2 · Sok Ching Cheong3,4 Received: 10 August 2020 / Revised: 28 September 2020 / Accepted: 13 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Generating a tissue model mimicking the cervix could be useful for studying treatment of precancerous lesions. In this work, bioprinting of hexagon shaped alginategelatin scaffolds laden with HeLa spheroids was presented. The three-dimensional (3D) printing system was designed to extrude alginate-gelatin bioink of different viscosities at an extrusion rate of 1–5 mL/min and printing speed from 10 to 50 mm/s. The biophysical properties of the bioink were characterized using dynamic mechanical analysis, viscometer, degradation test, contact angle measurement, Fourier transform infrared spectroscopy (FTIR), live/dead cell stainings and Raman spectroscopy. The bioink formulated with 10% w/v of alginate and 50% w/v of gelatin (ALG10-Gel50) enabled high fidelity printing for the construction of a multilayered 3D structure. The viscosity of the bioink within 12 Pa s and viscoelasticity of the polymerized bioink (G′ = 0.074 MPa > G″ = 0.028 MPa) exhibited mechanical properties close to the in-vivo system. The scaffolds degraded 35% on the day 16 of culture. The polymerized bioinks exhibited hydrophilicity and contained amino groups as characterized by contact angles and FTIR measurements, respectively. In addition, the 3D microtissues laden in the scaffold were indicated with high cell viability at 95.25 ± 1.75% based on the live/dead cell stainings. The printed microtissues were characterized with the presence of deoxyribonucleic acid, lipids and amino acids associated with the collagen. This paper demonstrated the success in the bioprinting of multilayer hexagon shaped tissue model which is potentially useful for development of an in-vitro cervical cancer model. Keywords Bioprinting · HeLa · Spheroids · Alginate · Gelatin · Bioink · 3D scaffolds
* Chin Fhong Soon [email protected] Extended author information available on the last page of the article
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Polymer Bulletin
Introduction In 2018, World health organization (WHO) reported that an estimate of 570,000 women were detected with cervical cancer and contributed to 311,000 death in women [1]. Cervical cancer developes in the cervix, which is cylindrical in shape and connects the uterus to the vagina. A previous study [2] has created an in-vitro cervical cancer model that could be applied for treating precancerous lesions but the model produced was in the form of square and flattened matrix [2, 3]. A model with cylindrical shape tissue model simulating the cervical structure could be created with the advancement of 3D printing technology. The ability to reproduce a computer aided design (CAD) model with consist
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