3D Bioprinting a Cell-Laden Bone Matrix for Breast Cancer Metastasis Study

Abstract

Metastasis is one of the deadliest consequences of breast cancer, with bone being one of the primary sites of occurrence. Insufficient 3D biomimetic models currently exist to replicate this process in vitro. In this study, we developed a biomimetic bone matrix using 3D bioprinting technology to investigate the interaction between breast cancer (BrCa) cells and bone stromal cells (fetal osteoblasts and human bone marrow mesenchymal stem cells (MSCs)). A tabletop stereolithography 3D bioprinter was employed to fabricate a series of bone matrices consisting of osteoblasts or MSCs encapsulated in gelatin methacrylate (GelMA) hydrogel with nanocrystalline hydroxyapatite (nHA). When BrCa cells were introduced into the stromal cell-laden bioprinted matrices, we found that the growth of BrCa cells was enhanced by the presence of osteoblasts or MSCs, whereas the proliferation of the osteoblasts or MSCs was inhibited by the BrCa cells. The BrCa cells co-cultured with MSCs or osteoblasts presented increased vascular endothelial growth factor (VEGF) secretion in comparison to that of monocultured BrCa cells. Additionally, the alkaline phosphatase activity of MSCs or osteoblasts was reduced after BrCa cell co-culture. These results demonstrate that the 3D bioprinted matrix, with BrCa cells and bone stromal cells, provides a suitable model with which to study the interactive effects of cells in the context of an artificial bone microenvironment and thus may serve as a valuable tool for the investigation of postmetastatic breast cancer progression in bone.

3D Miniaturization of Human Organs for Drug Discovery

“…High-throughput pharmacological study [36,78] 3D bioprinting Primary feline H1 cardiomyocytes First rhythmic beating of 3D printed structure [93][94][95] Lung Microfabrication Epithelial cells Use of porous membrane to mimic lung functions [31,37] 3D bioprinting A549 cells and EA hy926 cells World's first 3D bioprinted lung tissue [101] Bone 3D bioprinting BMSCs High viability in microextrusion-based bioprinting [108,109,158,159] Cancer Self-assembled Intestinal stem cells Discovery of LGR5+ intestinal stem cells [52,62] Microfabrication Breast cancer cells Perfusable human microvascularized bone-mimicking (BMi) microenvironment [81,168] 3D bioprinting OVCAR-5 and MRC-5 cells Insight into complex cell-cell communication in 3D [113][114][115][116][117] Multi Self-assembled Liver, gut, vessel cells High throughput hanging drop [30,[49][50][51][52] Microfabrication Liver, heart, and vessel cells Automated control of perfusion [11,19,27,32] 3D bioprinting NPC and HCT-116 cells Multiorgan bioprinted model [30,122] a)…”

“…[115] Other groups have generated different cancer 3D in vitro models including models for bone and breast cancers using 3D bioprinting. [116,117] …”

3D bioprinting of cell-laden hydrogels for advanced tissue engineering

“…Recently, a number of different tissue models to be used as drug and toxicity screening platforms have been fabricated using 3D bioprinting ( [67] and thrombosis [68] have been addressed.…”

Current developments in 3D bioprinting for tissue engineering

“…In the field of 3D bioprinting, two major groups of biomaterials for 3D printing can be determined. The first being a group of rigid curing materials, used mainly as a scaffold for cells, providing mechanical support; these materials include hydroxyapatite (HA) [13], calcium phosphate [14], Poly-(e-caprolactone) (PCL) [15], and others. Some of these materials are osteogenic and promote cell proliferation on their surface, making them perfect for 3D printing bone tissue [16].…”

“…However, not enough biomimetic models are available for research. Zhou et al [13] were able to research cancer metastasis into bone by 3D bioprinting a cell-laden bone matrix, providing a microenvironment that mimics native bone tissue. Using this model, they were able to research the morphology, migration and interaction with bone stromal cells of breast cancer cells.…”