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Tunable Hydrogel Platforms to Mimic Breast Cancer Microenvironments via 3D Bioprinting
1, 2 , 2 , 3 , 2, 4 , 2, 4 , * 1
1  Research Center on Advanced Biochemistry and Molecular Biology, Department of Experimental and Clinical Medicine, Magna Græcia University of Catanzaro, 88100 Catanzaro, Italy
2  Molecular Medicine Department , Centre for Health Technologies , Unità di Ricerca INSTM, Operative Unit of the Interuniversity Center for the Promotion of the 3Rs Principles in Teaching and Research , University of Pavia, 27100 Pavia, Italy
3  Department of Drug Sciences, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy
4  UOR6 Nanotechnology Lab., Department of Prevention and Rehabilitation in Occupational Medicine and Specialty Medicine, Istituti Clinici Scientifici Maugeri IRCCS,27100 Pavia, Italy.
Academic Editor: Vincenzo Guarino

Abstract:

Breast cancer remains a leading cause of mortality among women, yet conventional preclinical models often fail to replicate the structural and biomechanical features of native tumor tissue. Flat, two-dimensional cultures lack the three-dimensional cellular interactions necessary for accurate studies, while animal models frequently exhibit poor translational predictability. To overcome these limitations, we designed and optimized bioprintable hydrogel systems capable of mimicking the physical and structural properties of breast tumor microenvironments.

Sodium alginate (ALG) and gelatin (GEL) blends were formulated at varying concentrations and ionically crosslinked with calcium chloride to generate hydrogels with tunable stiffness in the range of pathological breast tissue. Their physical stability, pH behavior, and controlled degradation were systematically evaluated over a period of three weeks. Structural and chemical integrity were investigated through scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR), confirming the preservation of the alginate backbone and the successful integration of gelatin. Rheological studies provided insight into viscoelasticity and shear-thinning properties relevant to extrusion-based bioprinting, while printability assessments identified formulations suitable for the fabrication of stable constructs.

The resulting scaffolds exhibited interconnected porous networks, a storage modulus of approximating 10 kPa, and adequate viscosity profiles to sustain both print fidelity and cell viability. Together, these findings highlight ALG–GEL hydrogels as versatile platforms for recapitulating tumor-specific mechanical cues, supporting nutrient transport, and enabling the fabrication of reproducible, physiologically relevant three-dimensional breast cancer models. Future work integrating cancer cell lines will further validate their potential as advanced tools for oncological research and therapeutic testing.

Keywords: 3D Bioprinting; Breast Cancer; hydrogels
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