TY - JOUR
KW - 4D bioprinting
KW - Chemoresistance
KW - Duct-mimetic scaffolds
KW - Dynamic culture
AU - Sriram Bharath Gugulothu
AU - Kaushik Chatterjee
AB - Four-dimensional (4D) bioprinting offers a facile strategy for generating dynamic tissue constructs with physiologically relevant geometries for disease modeling. Here, we extend a previously established visible-light-crosslinkable hydrogel system to fabricate self-folding, duct-mimetic tubular constructs for triple-negative breast cancer (TNBC) modeling under dynamic culture conditions. Systematic optimization of photoinitiator concentration in bioink, scaffold thickness and length, cell density, and solvent conditions identified parameters that enabled robust self-folding of TNBC cell-laden constructs into closed thin-walled (≤ 0.8 mm) tubes with an internal diameter of ≈2.1 mm, comparable to those of mammary ducts. Nanoindentation confirmed a stable mechanical gradient in the tubular scaffolds over 14 days, with a softer outer surface (≈0.5 kPa) and a stiffer inner surface (≈20 kPa). Under rocker-based dynamic culture, MDA-MB-231-laden tubular constructs showed improved viability and a 1.4-fold increase in metabolic activity compared with their static culture counterparts at Day 14. Dynamic culture also promoted the appearance of mesenchymal-like spindle morphology by Day 7 and cellular aggregation by Day 14. Following doxorubicin treatment at Day 14, dynamically cultured tubes exhibited enhanced chemoresistance compared to static constructs, with lower cell death (65%vs. 75%) at approximately 10-fold higher half-maximal inhibitory concentration (IC50) (10 µM). Together, these findings establish a 4D-bioprinted TNBC model with a duct-like architecture and mechanical anisotropy to investigate the role of passive (stiffness gradients) and dynamic (interstitial flow) biophysical cues on tumor cell behavior and therapeutic response.
BT - Engineered Regeneration
DA - 2026-01-01
DO - 10.1016/j.engreg.2026.07.002
N2 - Four-dimensional (4D) bioprinting offers a facile strategy for generating dynamic tissue constructs with physiologically relevant geometries for disease modeling. Here, we extend a previously established visible-light-crosslinkable hydrogel system to fabricate self-folding, duct-mimetic tubular constructs for triple-negative breast cancer (TNBC) modeling under dynamic culture conditions. Systematic optimization of photoinitiator concentration in bioink, scaffold thickness and length, cell density, and solvent conditions identified parameters that enabled robust self-folding of TNBC cell-laden constructs into closed thin-walled (≤ 0.8 mm) tubes with an internal diameter of ≈2.1 mm, comparable to those of mammary ducts. Nanoindentation confirmed a stable mechanical gradient in the tubular scaffolds over 14 days, with a softer outer surface (≈0.5 kPa) and a stiffer inner surface (≈20 kPa). Under rocker-based dynamic culture, MDA-MB-231-laden tubular constructs showed improved viability and a 1.4-fold increase in metabolic activity compared with their static culture counterparts at Day 14. Dynamic culture also promoted the appearance of mesenchymal-like spindle morphology by Day 7 and cellular aggregation by Day 14. Following doxorubicin treatment at Day 14, dynamically cultured tubes exhibited enhanced chemoresistance compared to static constructs, with lower cell death (65%vs. 75%) at approximately 10-fold higher half-maximal inhibitory concentration (IC50) (10 µM). Together, these findings establish a 4D-bioprinted TNBC model with a duct-like architecture and mechanical anisotropy to investigate the role of passive (stiffness gradients) and dynamic (interstitial flow) biophysical cues on tumor cell behavior and therapeutic response.
PY - 2026
SP - 121
EP - 134
T2 - Engineered Regeneration
TI - Dynamic 4D-bioprinted duct-like microenvironments for triple-negative breast cancer modeling and drug response
UR - https://www.sciencedirect.com/science/article/pii/S2666138126000113
VL - 7
Y2 - 2026-07-23
SN - 2666-1381
ER -