3D bioprinted breast tumor model for structure–activity relationship study

Abstract

In this paper, we present a 3D printed tumor spheroidal model suitable for drug discovery. This model is based on a hydroxyethyl cellulose/alginate/gelatin (HCSG) composite biomaterial that has three distinct properties: (1) the HCSG is similar to the commercial basement membrane extract in Ki67, MUC1, and PARP1 expressions of MCF-7 cells for embedding culture; (2) the HCSG is printable at room temperature; and (3) the HCSG can be large-scale manufactured at an ultralow cost.We printed a 3D MCF-7 spheroid model with HCSG and characterized it in terms of cell viability, spheroid size, key protein expression, and mitochondrial metabolic activity. We used the 3D MCF-7 spheroid model to evaluate the anti-breast cancer activity of 13 amino acid-based flavone phosphoramidates and found that the alanine structure induced a stronger drug resistance, whereas phenylalanine hardly caused drug resistance in the MCF-7 cells. This is the first time that 3D bioprinting technology has been used in a structure-activity relationship study.

Decellularized Pig Kidney with a Micro-Nano Secondary Structure Contributes to Tumor Progression in 3D Tumor Model

“…This result was consistent with the report that different densities of cells resulted in different spheroid sizes, and the spheroid area of cells at the density of 45,000 cells/well turned out to be 6.0 × 10 6 μm 2 [ 54 ]. Reports showed that the size of tumor spheroids could be controlled at around 200 μm after 7 to 8 days when grown in microwells, which was the largest [ 55 , 56 ]. In this study, the size of the tumor sphere increased from day 3 to day 21, indicating that the platform simulated the process of tumor formation more realistically.…”

3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

“…A proof-of-concept study utilizing bioprinted breast cancer constructs was reported by Li et al. [136] . Using a hydroxyethyl cellulose/alginate/gelatin hydrogel and MCF-7-based spheroid bioprinted construct, the anti-breast cancer activity of phosphoramidates (13 amino acid-containing flavone) was examined and the results indicated that alanine structure induced a stronger drug resistance than phenylalanine in the MCF-7 cells.…”

A Guide to Polysaccharide-Based Hydrogel Bioinks for 3D Bioprinting Applications

“…The high diversity of chemical structures and properties of these plant polysaccharides opens the possibility for their application in several fields, including in the food area (e.g., as gelling agents) [ 97 ], in the biomedical field (e.g., in drug delivery systems) [ 98 ], and, more recently, in tissue engineering [ 99 ]. The interest in using some of these plant-derived polysaccharides in the formulation of bioinks for 3D bioprinting applications has also grown considerably in the later years, as summed up in Table 2 , with several works using cellulose and nanocelluloses [ 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 ] and pectin [ 119 , 120 ].…”

“…The use of cellulose derivatives for the development of bioinks has been recently reviewed [ 126 , 127 ], and it is mainly focused on the exploitation of CMC. However, other cellulose derivatives, such as methyl cellulose [ 101 ], hydroxyethylcellulose [ 112 ], and hydroxypropyl methyl cellulose [ 113 , 114 ], are also starting to be studied in this context. For instance, Ni et al [ 114 ] mixed silk fibroin with hydroxypropyl methyl cellulose, that was previously methacrylated, in different proportions (3:1, 2:2 and 1:3) to bioprint, through extrusion, bone marrow-derived mesenchymal stromal cells (BMSC)-laden double network hydrogels for cartilage tissue repair, as seen in Figure 3 A.…”