Silicone cryogel skeletons enhance the survival and mechanical integrity of hydrogel-encapsulated cell therapies-Reference-Cited by-同舟云学术

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

Published:2024-04-05 Issue:14 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Jeang William J.¹²³^ORCID,Bochenek Matthew A.²³⁴^ORCID,Bose Suman²³⁴⁵^ORCID,Zhao Yichao²³⁴^ORCID,Wong Bryan M.⁶,Yang Jiawei²³⁴⁷^ORCID,Jiang Alexis L.⁸,Langer Robert²³⁴⁹¹⁰^ORCID,Anderson Daniel G.²³⁴⁹¹⁰^ORCID

Affiliation:

1. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

2. David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

3. Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Boston, MA 02115, USA.

4. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

5. Department of Physiology and Biomedical Engineering, Mayo Clinic, Scottsdale, AZ 85259, USA.

6. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

7. Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USA.

8. Department of Computer Science, Wellesley College, Wellesley, MA 02481, USA.

9. Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

10. Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adk5949

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