Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low‐Concentration Collagen‐Based Bioinks

Abstract

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models challenging. This work produces embedded, bioprinted breast cancer cells and tumor organoid models using low‐concentration collagen I based bioinks. The biocompatible and physically crosslinked silk fibroin hydrogel is used to generate the support bath for the embedded 3D printing. The composition of the collagen I based bioink is optimized with a thermoresponsive hyaluronic acid‐based polymer to maintain the phenotypes of both the noninvasive epithelial and invasive breast cancer cells, as well as cancer‐associated fibroblasts. Mouse breast tumor organoids are bioprinted using optimized collagen bioink to mimic in vivo tumor morphology. A vascularized tumor model is also created using a similar strategy, with significantly enhanced vasculature formation under hypoxia. This study shows the great potential of embedded bioprinted breast tumor models utilizing a low‐concentration collagen‐based bioink for advancing the understanding of tumor cell biology and facilitating drug discovery research.

Embedded bioprinted multicellular spheroids modeling pancreatic cancer bioarchitecture towards advanced drug therapy

“…36 Additionally, the gelatin hydrogel was introduced here mainly as an auxiliary phase to promote the extrusion printing of low-concentration collagen solutions, because low-concentration collagen solutions are commonly mechanically weak and have low viscosity, which makes the extrusion printing of a single collagen component very challenging. 37,38 On the other hand, the thermosensitive gelatin served as a sacrificial phase owing to its ability to liquefy at 37 °C post-printing. In the incubator, the sacrificial gelatin melted while the collagen gradually crosslinked, which synergistically facilitated the process of cell assembly within the GelMA bath.…”

Embedded 3D bioprinting – An emerging strategy to fabricate biomimetic & large vascularized tissue constructs

“…Support bath materials are very helpful in preventing the collapse of printed three–dimensional complex structures. Several studies have reported the use of various synthetic materials such as Laponite, Carbopol, Pluronic F127 and natural materials like agarose, alginate, silk fibroin and gelatin in support bath systems to fabricate complex organs using extrusion–based bioprinting [ 36 , 49 , 54 , 57 , 59 , 142 ].…”

“…Moreover, tumor organoids were developed by printing breast cancer cells in the core region and fibroblast cells in the peripheral region. Among the three bioinks (C, CH, M), CH bioink uniquely preserved the phenotypic characteristics of both epithelial tumor cells and fibroblasts due to their ability to replicate the in vivo breast cancer tumor microenvironment demonstrating the importance of extracellular matrix (ECM) components in the fidelity of tumor models [ 142 ]. In another study, Maloney et al, used embedded bioprinting technology to screen chemotherapeutic drugs for HepG2, Caco2, and patient–derived glioblastoma and sarcoma.…”

3D bioprinting platform development for high-throughput cancer organoid models construction and drug evaluation

“…The utilization of the Matrigel in 3D bioprinting of organoids remained relatively limited [24], with most studies opting for direct use of conventional bioinks for printing and culturing tumor organoids. However, this approach often failed to provide optimal growth conditions for the organoids, thereby compromising their viability during the cultivation process and influencing experimental outcomes [13,25]. In contrast, this work had developed a composite bioink that not only meets the requirements for excellent printability but also maximally preserves the activity of tumor organoids, thus enabling superior construction of in vitro models.…”