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.

A Synthetic Hydrogel, VitroGel® ORGANOID-3, Improves Immune Cell-Epithelial Interactions in a Tissue Chip Co-Culture Model of Human Gastric Organoids and Dendritic Cells

“…Because of these multiple limitations of Matrigel as an ECM material, recent studies have analyzed alternative natural and synthetic hydrogels for different tissue culture applications ( Aisenbrey and Murphy, 2020 ; Kaur et al, 2021 ). In this work, we used a commercially available synthetic hydrogel, VitroGel ® ORGANOID 3 (V-ORG-3) ( Gebeyehu et al, 2021 ), which sustained HGO viability and growth while eliminating the batch-to-batch variation of Matrigel.…”

“…We used Matrigel (#354234, Corning, Corning, NY), rat tail collagen type I (#354-236, Corning, Bedford, MA, United States) and commercially available synthetic hydrogels, VitroGel ® ORGANOID 1-4 (#VHM04-K, TheWell Bioscience, NJ) as extracellular matrix materials. VitroGels ® are xeno-free polysaccharide-based hydrogels designed for 3-D tissue cultures that have been used in a number of cancer studies (Pang et al, 2019;Haruna and Huang, 2020;Gebeyehu et al, 2021;Wang et al, 2021). The VitroGel ® ORGANOID (V-ORG) Discovery Kit includes four types of organoid hydrogels (V-ORG-1-4) which contain proprietary formulations of various bio-functional ligands and which have different mechanical strengths and degradability to fulfill the needs of different organoid culture conditions.…”

Telmisartan Facilitates the Anticancer Effects of CARP-1 Functional Mimetic and Sorafenib in Rociletinib Resistant Non-small Cell Lung Cancer

“…This is further supported by a cell uptake study, which showed that Tel pre-treatment significantly increased the uptake of FITC in 3D spheroids when compared to free FITC stained 3D spheroids as analyzed by flow cytometry. Decreased diffusion of chemotherapeutics through the spheroids contribute to resistance in 3D spheroid cultures, and tumor penetration remains a vital barrier inhibiting treatment response (52).…”

3D Printing and Bioprinting to Model Bone Cancer: The Role of Materials and Nanoscale Cues in Directing Cell Behavior

“…These models showed a drug response to cisplatin similar to the in vivo model, thus supporting the use of 3D printing for drug testing. This possibility was also confirmed in other types of cancers, such as cervical [177], brain [60,178], lung [179], and bladder [179,180]. The quick rising of novel bioprinted models of several types of cancer for drug screening and personalized medicine approaches, as well as the increasing trend of publications on bone models for oncology (Figure 3), clearly indicates that numerous studies will be published in the upcoming years for bone tumors as well.…”