Construction of a 3D Bioprinted Microfluidic Platform to Study Breast Cancer Bone Metastasis and Tumor Microenvironmental Influences

TL;DR

Researchers created a 3D bioprinted platform to study how breast cancer spreads to bone, mimicking the tumor and bone environments to better understand and treat metastasis.

Contribution

The novel contribution is a 3D bone metastasis-on-a-chip platform that mimics tumor and bone microenvironments with adjustable stiffness and bioinks.

Findings

A 3D bioprinted platform was developed to replicate breast cancer tumor, vascular, and bone microenvironments.

Bioinks with adjustable stiffness supported tumor spheroid growth and enhanced metastatic potential through stemness and EMT.

The platform successfully simulated BrCa cell migration and colonization in a bone-like matrix.

Abstract

Breast cancer (BrCa) frequently metastasizes to bone,
severely
compromising patient survival. Preventing metastatic spread is, therefore,
a crucial therapeutic goal. Tumor matrix stiffness, growth factor
gradients, and the bone microenvironment collectively influence cancer
progression; however, existing in vitro models lack
the physiological complexity to capture these interactions. To address
this, we developed a 3D biomimetic bone metastasis-on-a-chip platform
to recapitulate the key microenvironments involved in BrCa dissemination.
This study aimed to develop an in vitro metastasis
chip that mimics BrCa tumors, the vascular-like region, and the bone
microenvironment, enabling investigation of microenvironmental factors
during metastasis. Bioinks replicating tumor microenvironments with
adjustable stiffness were synthesized, including methacrylated collagen
(ColMA) and hyaluronic acid (HAMA). Their chemical, mechanical, and
biocompatible properties were optimized. Selected bioinks mimicked
BrCa stiffness, allowing tumor spheroid embedding in a two-layered
model. The core bioink promoted BrCa proliferation, while the peripheral
bioink enhanced stemness and epithelial–mesenchymal transition
(EMT), increasing metastatic potential. Furthermore, a 3D bone-like
matrix composed of methacrylated gelatin and hydroxyapatite was integrated
to simulate the extravasation process, facilitating BrCa cell migration
and colonization within the bone-mimicking region. This metastasis-on-a-chip
system successfully replicates critical stages of BrCa progression
and provides a versatile in vitro platform for studying
metastatic mechanisms and evaluating potential antimetastatic therapies.

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