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

Sci Adv. 2024 Apr 5;10(14):eadk5949. doi: 10.1126/sciadv.adk5949. Epub 2024 Apr 5.

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.

MeSH terms

  • Alginates
  • Animals
  • Cell Survival
  • Cryogels*
  • Hydrogels*
  • Mice
  • Oxygen
  • Silicones
  • Skeleton

Substances

  • Hydrogels
  • Cryogels
  • Silicones
  • Alginates
  • Oxygen