Silicone cryogel skeletons enhance the survival and mechanical integrity of hydrogel-encapsulated cell therapies.

Jeang, William J; Bochenek, Matthew A; Bose, Suman; Zhao, Yichao; Wong, Bryan M; Yang, Jiawei; Jiang, Alexis L; Langer, Robert et al. · Sci Adv · 2024

basic_science · Level V

Where this comes from

Abstract

The transplantation of engineered cells that secrete therapeutic proteins presents a promising method for addressing a range of chronic diseases. However, hydrogels used to encase and protect non-autologous cells from immune rejection often suffer from poor mechanical properties, insufficient oxygenation, and fibrotic encapsulation. Here, we introduce a composite encapsulation system comprising an oxygen-permeable silicone cryogel skeleton, a hydrogel matrix, and a fibrosis-resistant polymer coating. Cryogel skeletons enhance the fracture toughness of conventional alginate hydrogels by 23-fold and oxygen diffusion by 2.8-fold, effectively mitigating both implant fracture and hypoxia of encapsulated cells. Composite implants containing xenogeneic cells engineered to secrete erythropoietin significantly outperform unsupported alginate implants in therapeutic delivery over 8 weeks in immunocompetent mice. By improving mechanical resiliency and sustaining denser cell populations, silicone cryogel skeletons enable more durable and miniaturized therapeutic implants.

Medical subject headings