Jimenez de Aberasturi, D. | bioRxiv Science

bioRxiv2026

Lung-mimicking click alginate-dECM model of breast cancer lung metastasis reveals the role of ECM mechanics in tumor growth dynamics and genomic instability

Metastatic breast cancer (BC) is the main cause of cancer-related death in women. Accumulating evidence highlights the prominent changes within the lung metastatic niche, resulting in stiffening of the extracellular matrix (ECM). The prevailing concept of cancer evolution encompasses the acquisition of beneficial traits as a consequence of genomic instability, yet it remains elusive to what extend altered lung ECM mechanics feed into this. To investigate this, a tunable 3D bioengineered model, capturing the biophysical and biochemical characteristics of the BC metastatic lung niche is developed. Porcine derived lung decellularized ECM (dECM), combined with norbornene and tetrazine modified click-crosslinkable alginate, recapitulates composition and mechanics of healthy soft (3 kPa) and metastatic stiff (13 kPa) lung niches. Label-free optical microscopy further validates the microarchitectural resemblance between resulting matrices and human lung metastasis samples. Encapsulation of MDA-MB-231 and MCF7 cells reveals that stiffer matrices promote BC cluster growth and DNA damage, indicated by yH2AX, independent of BC subtype. Moreover, this platform is compatible with patient derived cells, which remain viable for 14 days. These findings underscore the critical role of tissue mechanics in regulating BC metastasis progression and demonstrate the utility of the herein developed tunable, physiologically relevant platform for patient-based models. Table of Content O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=180 SRC="FIGDIR/small/698349v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@19a164dorg.highwire.dtl.DTLVardef@12e1c1aorg.highwire.dtl.DTLVardef@371378org.highwire.dtl.DTLVardef@1df3ddb_HPS_FORMAT_FIGEXP M_FIG C_FIG Fabrication of 3D bioengineered breast cancer (BC) lung metastasis niche to investigate how tissue mechanics modulate cancer evolution. Tunable hybrid biomaterials recapitulate the mechanical and biochemical characteristics of healthy soft and diseased stiff lung. Within these niches, stiffness promotes enhanced BC cluster growth and genomic instability. Biocompatibility with patient-derived BC cells, opens opportunities for drug testing platforms for personalized medicine.

bioengineering↗

bioRxiv2025

Hybrid bioinks for embedded bioprinting of an artery model

The integration of biomaterials with living cells and stimuli-responsive materials can be employed to create bioinks capable of generating 3D in vitro models that better recapitulate native tissues. We introduce a multilayered artery model that combines hybrid multifunctional materials including a stimuli-responsive polymeric ink to mimic the tunica adventitia arterial wall, and an extracellular matrix (ECM)-based bioink for the tunica media artery layer. The stimuli-responsive hybrid layer integrates inorganic (plasmonic nanoparticles) and organic (polymers) components, providing structural support and introducing diverse functionalities to the system. The cell-laden bioink consists of human vascular smooth muscle cells (vSMC) within a hydrogel based on porcine artery-derived decellularized extracellular matrix (dECM) that fosters optimal cell growth and proliferation. An embedding bioprinting technique was employed for the fabrication of the multimaterial artery model consisting of concentric cylinders. The dimensions of the 3D model and the bioprinting parameters were fine-tuned to ensure effective crosslinking of the multiple concentric layers resulting in the creation of self-supporting constructs. We demonstrate the effectiveness of the hybrid bioink composition and bioprinting parameters in supporting cell viability and proliferation within the multilayered construct, expanding the possibilities of employing novel multi-component materials for the fabrication of 3D vasculature models resembling the structure of native blood vessels.

bioengineering↗