Tunable enhancement of T cell expansion through modulation of stiffness and adhesion receptor engagement in an engineered hydrogel platform
Author(s)
Type
Journal Article
Abstract
Adoptive T cell therapies (ACT) are an important class of oncology treatments that require ex vivo T cell expansion for clinical success. Technologies that can control both phenotype and yield in expanded cell products are highly desired. Here, we develop a new hydrogel scaffold for controlled T cell expansion with yields of up to 2000× fold in two weeks, compared to other hydrogel constructs (≈250×) and Dynabeads (≈1200×). Our 2D polyethylene glycol diacrylate (PEGDA) hydrogel scaffold is cross-linked with streptavidin moieties to present various biotinylated ligands to cells with controlled hydrogel stiffness (PEGDA-Strep). Using this platform, we demonstrate that combining substrate stiffness with adhesion receptor ligands (aLFA-1 or aCD2) dictates T cell activation and proliferation. On stiff substrates, these ligands drove expansions 49% (aLFA-1) and 68% (aCD2) greater than Dynabeads with comparable T cell products, preceded by elevated metabolic and transcriptional activity. Notably, while stiff substrates increased yield, soft substrates produced T cells with superior antigen-specific killing selectivity. These findings highlight the role of mechanical sensing in T cell-APC interactions and suggest improved manufacturing methods for adoptive T cell therapy (ACT).
Date Issued
2026-02-20
Date Acceptance
2025-12-18
Citation
Advanced Materials, 2026, 38 (11)
ISSN
0935-9648
Publisher
Wiley
Journal / Book Title
Advanced Materials
Volume
38
Issue
11
Copyright Statement
© 2026 The Author(s). Advanced Materials published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Identifier
10.1002/adma.202505965
Subjects
adhesion receptor
CD2
expansion
hydrogels
LFA-1
mechanosensing
T cell
Publication Status
Published
Article Number
e05965
Date Publish Online
2026-01-08