Posted by This work establishes the design of a fully synthetic, shear-thinning hydrogel platform that is injectable and can isolate engineered, allogeneic cell therapies from the host. RAFT was utilized to generate a library of linear random copolymers of N,N-dimethylacrylamide (DMA) and 2-vinyl-4,4-dimethyl azlactone (VDMA) with variable mol% VDMA and degree of polymerization. Poly(DMA-co-VDMA) copolymers were subsequently modified with either adamantane or β-cyclodextrin through amine-reactive VDMA to prepare hydrogel precursor macromers containing complementary guest-host pairing pendant groups that, when mixed, form shear-thinning hydrogels.
In studies benchmarking against alginate, a material traditionally used for cell encapsulation, the lead hydrogel showed significantly less fibrous encapsulation in a subcutaneous implant site. Finally, this platform was utilized to encapsulate and extend in vivo longevity of inducible transgene-engineered mesenchymal stem cells in an allogeneic transplant model. The hydrogels remained intact and blocked infiltration by host cells, consequently extending the longevity of grafted cell function relative to a benchmark, shear-thinning hyaluronic acid-based gel.
Mariah G. Bezold, Bryan R. Dollinger, Carlisle R. DeJulius, Megan C. Keech, Andrew R. Hanna, Anna R. Kittel, Fang Yu, Mukesh K. Gupta, Richard D’Arcy, Jonathan M. Brunger, Craig L. Duvall,
Shear-thinning hydrogel for allograft cell transplantation and externally controlled transgene expression.
Biomaterials 314, 2025, 122812. https://doi.org/10.1016/j.biomaterials.2024.122812.