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

Autor: Jeang WJ; Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA., Bochenek MA; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Bose S; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Physiology and Biomedical Engineering, Mayo Clinic, Scottsdale, AZ 85259, USA., Zhao Y; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Wong BM; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Yang J; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Mechanical and Materials Engineering, Worcester Polytechnic Institute, Worcester, MA 01609, USA., Jiang AL; Department of Computer Science, Wellesley College, Wellesley, MA 02481, USA., Langer R; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Anderson DG; David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA 02115, USA.; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.; Harvard-MIT Program in Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2024 Apr 05; Vol. 10 (14), pp. eadk5949. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1126/sciadv.adk5949
Abstrakt: 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.
Databáze: MEDLINE