3D bioprinted breast cancer model reveals stroma-mediated modulation of extracellular matrix and radiosensitivity.

Deciphering breast cancer treatment resistance remains hindered by the lack of models that can successfully capture the four-dimensional dynamics of the tumor microenvironment. Here, we show that microextrusion bioprinting can reproducibly generate distinct cancer and stromal compartments integrating cells relevant to human pathology. Our findings unveil the functional maturation of this millimeter-sized model, showcasing the development of a hypoxic cancer core and an increased surface proliferation. Maturation was also driven by the presence of cancer-associated fibroblasts (CAF) that induced elevated microvascular-like structures complexity. Such modulation was concomitant to extracellular matrix remodeling, with high levels of collagen and matricellular proteins deposition by CAF, simultaneously increasing tumor stiffness and recapitulating breast cancer fibrotic development. Importantly, our bioprinted model faithfully reproduced response to treatment, further modulated by CAF. Notably, CAF played a protective role for cancer cells against radiotherapy, facilitating increased paracrine communications. This model holds promise as a platform to decipher interactions within the microenvironment and evaluate stroma-targeted drugs in a context relevant to human pathology.

Harnessing Human Placental Membrane-Derived Bioinks: Characterization and Applications in Bioprinting and Vasculogenesis.

Bioprinting applications in the clinical field generate great interest, but developing suitable biomaterial inks for medical settings is a challenge. Placental tissues offer a promising solution due to their abundance, stability, and status as medical waste. They contain basement membrane components, have a clinical history, and support angiogenesis. This study formulates bioinks from two placental tissues, amnion (AM) and chorion (CHO), and compares their unique extracellular matrix (ECM) and growth factor compositions. Rheological properties of the bioinks are evaluated for bioprinting and maturation of human endothelial cells. Both AM and Cho-derived bioinks sustained human endothelial cell viability, proliferation, and maturation, promoting optimal vasculogenesis. These bioinks derived from human sources have significant potential for tissue engineering applications, particularly in supporting vasculogenesis. This research contributes to the advancement of tissue engineering and regenerative medicine, bringing everyone closer to clinically viable bioprinting solutions using placental tissues as valuable biomaterials.

Bone Laser Patterning to Decipher Cell Organization.

The laser patterning of implant materials for bone tissue engineering purposes has proven to be a promising technique for controlling cell properties such as adhesion or differentiation, resulting in enhanced osteointegration. However, the possibility of patterning the bone tissue side interface to generate microstructure effects has never been investigated. In the present study, three different laser-generated patterns were machined on the bone surface with the aim of identifying the best surface morphology compatible with osteogenic-related cell recolonization. The laser-patterned bone tissue was characterized by scanning electron microscopy and confocal microscopy in order to obtain a comprehensive picture of the bone surface morphology. The cortical bone patterning impact on cell compatibility and cytoskeleton rearrangement on the patterned surfaces was assessed using Stromal Cells from the Apical Papilla (SCAPs). The results indicated that laser machining had no detrimental effect on consecutively seeded cell metabolism. Orientation assays revealed that patterns with larger hatch distances were correlated with higher cell cytoskeletal conformation to the laser-machined patterns. To the best of our knowledge, this study is the first to consider and evaluate bone as a biological interface that can be engineered for improvement. Further investigations should focus on the in vivo implications of this direct patterning.