Microphysiological Solid Tumor Models in Hydrogel Beads for CAR T Cell Immunotherapy Evaluation

Peng X, Janicijevic Z, et al.

Advanced Science

Helmholtz-Zentrum Dresden-Rossendorf, TU Dresden

RESEARCH SUMMARY

This study establishes a tunable 3D micrometastatic tumor model using PEGDA hydrogel beads for in vitro evaluation of chimeric antigen receptor (CAR) T cell therapy. The system replicates soft-tissue microenvironments (elastic modulus 0.3–0.6 kPa) by combining prostate stem cell antigen (PSCA)-expressing prostate cancer cells and fibroblast activation protein (FAP)-producing stromal cells in droplet-fabricated PEGDA microbeads. Co-culture modulated spheroid morphology, FAP secretion, and extracellular matrix remodeling, yielding tumor microstructures that recapitulate in vivo metastasis and immunosuppressive conditions. CAR T cell infiltration studies revealed that dual targeting of PSCA and FAP antigens significantly improved migration and cytotoxicity compared to single-antigen strategies, mirroring clinical resistance mechanisms in solid tumors.

Elastic modulus testing of PEGDA hydrogel beads was performed using a CellScale MicroTester G2 to assess bead stiffness and verify the physical tunability of the microenvironment. Beads were tested in DPBS at 37 °C using a 1 mm × 1 mm compression plate attached to a 0.1524 mm tungsten beam under 25 % strain at 30 µm s⁻¹. The recorded force–displacement data were used to generate stress–strain curves and compute **Young’s modulus (E = Δσ / Δε)**. The hydrogel beads exhibited stiffness values of 300–600 Pa, comparable to soft organs such as liver and lung. MicroTester G2 analysis validated matrix mechanical fidelity and underpinned the dual-target CAR T cell assay’s physiological relevance.

AUTHORS

Xuan Peng, Željko Janicijević, Liliana R. Loureiro, Lydia Hoffmann, Poh Soo Lee, Isli Cela, Benjamin Kruppke, Alexandra Kegler, Anja Feldmann, Ielizaveta Gorodetska, Anja Madleine Markl, Anna Dubrovska, Anne Kathrin Offermann, Michael Bachmann, Larysa Baraban.

PUBLICATION DETAILS

JOURNAL

Advanced Science

YEAR

2025

INSTITUTIONS

Helmholtz-Zentrum Dresden-Rossendorf, TU Dresden

COUNTRIES

Germany

INSTRUMENT USED

MicroTester

TESTING METHODS

Compression TestingHydrated and Temperature Controlled TestingMicro-Mechanical Testing

RESEARCH APPLICATIONS

Cancer MechanobiologyDrug Screening & Drug Delivery MechanicsHydrogel Mechanical TestingMechanotransductionMicrotissue and Spheroid MechanicsOrgan-On-A-Chip Systems

Related Publications:

Instrument Used:

Year:

Testing Method:

Research Application:

Country:

Dynamic Compression of Spheroid-Laden Alginate Granular Composites Induces Hypertrophic Chondrocyte Phenotype

Ramos-Rodriguez DH, Filler AC, et al.

bioRxiv Preprint

MicroTester

Compression TestingMicro-Mechanical Testing

Bone Tissue Engineering & MechanicsCartilage and Meniscus MechanicsMechanotransductionMicrotissue and Spheroid MechanicsScaffold Mechanical Testing

2026

3D Printing of Oxygen-Sensing ECM-Based Skin Graft for Personalized Treatment of Chronic Wounds—A Technological Proof of Concept

Zur Y, Hayam R, et al.

Journal of Functional Biomaterials

MicroTester

Compression TestingHydrated and Temperature Controlled TestingMicro-Mechanical TestingUltra Low Force Testing

3D Bioprinting & Bioink Materials TestingECM & Decellularized Matrix MechanicsScaffold Mechanical TestingSkin and Wound Healing Biomechanics

2026

Synthetically acetylated alginate is a superior in vitro biofilm model for antibiotic testing showing reduced tobramycin affinity

Schandl S, Osondu-Chuka G, et al.

European Polymer Journal

MicroTester

Compression TestingHydrated and Temperature Controlled TestingMicro-Mechanical Testing

Drug Screening & Drug Delivery MechanicsHydrogel Mechanical TestingMicrotissue and Spheroid MechanicsPolymers and Elastomers Testing

2025