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Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening.

ABSTRACT: A series of stable and ready-to-use bioinks have been developed based on the xeno-free and tunable hydrogel (VitroGel) system. Cell laden scaffold fabrication with optimized polysaccharide-based inks demonstrated that Ink H4 and RGD modified Ink H4-RGD had excellent rheological properties. Both bioinks were printable with 25-40 kPa extrusion pressure, showed 90% cell viability, shear-thinning and rapid shear recovery properties making them feasible for extrusion bioprinting without UV curing or temperature adjustment. Ink H4-RGD showed printability between 20 and 37 °C and the scaffolds remained stable for 15 days at temperature of 37 °C. 3D printed non-small-cell lung cancer (NSCLC) patient derived xenograft cells (PDCs) showed rapid spheroid growth of size around 500 µm in diameter and tumor microenvironment formation within 7 days. IC₅₀ values demonstrated higher resistance of 3D spheroids to docetaxel (DTX), doxorubicin (DOX) and erlotinib compared to 2D monolayers of NSCLC-PDX, wild type triple negative breast cancer (MDA-MB-231 WT) and lung adenocarcinoma (HCC-827) cells. Results of flow property, shape fidelity, scaffold stability and biocompatibility of H4-RGD suggest that this hydrogel could be considered for 3D cell bioprinting and also for in-vitro tumor microenvironment development for high throughput screening of various anti-cancer drugs.

SUBMITTER: Gebeyehu A

PROVIDER: S-EPMC7801509 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening.

Gebeyehu Aragaw A Surapaneni Sunil Kumar SK Huang John J Mondal Arindam A Wang Vivian Ziwen VZ Haruna Nana Fatima NF Bagde Arvind A Arthur Peggy P Kutlehria Shallu S Patel Nil N Rishi Arun K AK Singh Mandip M

Scientific reports 20210111 1

A series of stable and ready-to-use bioinks have been developed based on the xeno-free and tunable hydrogel (VitroGel) system. Cell laden scaffold fabrication with optimized polysaccharide-based inks demonstrated that Ink H4 and RGD modified Ink H4-RGD had excellent rheological properties. Both bioinks were printable with 25-40 kPa extrusion pressure, showed 90% cell viability, shear-thinning and rapid shear recovery properties making them feasible for extrusion bioprinting without UV curing or ...[more]

PMID: 33431915

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Project description:In biotechnology, immobilization of functional reactants is often done as a surface immobilization on small particles. Examples are chromatography columns and fixed-bed reactors. However, the available surface for immobilization is directly linked to particle diameter and bed porosity for these systems, leading to high backpressure for small particle sizes. When larger molecules, such as enzymes are immobilized, physical entrapment within porous materials like hydrogels is an alternative. An emerging technique for the production of geometrically structured, three-dimensional and scalable hollow bodies is 3D-printing. Different bioprinting methods are available to produce structures of the desired size, resolution and solids content. However, in case of entrapped enzymes mass transfer limitations often determine the achievable reactivities. With increasing complexity of the system, for example a fixed-bed reactor, 3D-simulation is indispensable to understand the local reaction conditions to be able to highlight the optimization potential. Based on experimental data, this manuscript shows the application of the dimensionless numbers effectiveness factor and Thiele modulus for the design of a 3D-printed flow-through reactor. Within the reactor, enzymes are physically entrapped in 3D-printed hydrogel lattices. The local reaction rate of the enzymes is directly dependent on the provided substrate amount at the site of reaction which is limited by the diffusion properties of the hydrogel matrix and the diffusion distance. All three parameters can be summed up by one key figure, the Thiele modulus, which, in short, quantifies mass transfer limitations of a catalytic system. Depending on the rate of the enzymatic reaction in correlation to the diffusional transport, mass transfer limitations will shift the optimum of the system, favoring slow enzyme kinetics and small diffusion distances. Comparison with the enzymatic reaction rate in solution yields the effectiveness factor of the system. As a result, the optimization potential of varying the 3D-printed geometries or the reaction rate within the experimentally available design space can be estimated.

Dataset Information

Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening.

Publications

Polysaccharide hydrogel based 3D printed tumor models for chemotherapeutic drug screening.

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