IL-10-Functionalized Hydrogels Support Immunosuppressive Dendritic Cell Phenotype and Function

Autor: Nicholas M. Beskid, Elizabeth M. Kolawole, María M. Coronel, Brandon Nguyen, Brian Evavold, Andrés J. García, Julia E. Babensee
Rok vydání: 2022
Předmět:
Zdroj: ACS Biomater Sci Eng
ISSN: 2373-9878
DOI: 10.1021/acsbiomaterials.2c00465
Popis: Biomaterial systems such as hydrogels enable localized delivery and post-injection modulation of cellular therapies in a wide array of contexts. Biomaterials as adjuvants has been an active area of investigation, but the study of functionalized biomaterials supporting immunosuppressive cell therapies for tolerogenic applications is still nascent. Here, we developed a 4-arm poly(ethylene-glycol)-maleimide (PEG-4MAL) hydrogel functionalized with interleukin-10 (IL-10) to improve the local delivery and efficacy of a cell therapy against autoimmune disease. The biophysical and biochemical properties of PEG-4MAL hydrogels were optimized to support dendritic cell (DC) viability and an immature phenotype. IL-10-functionalized PEG-4MAL (PEG-IL10) hydrogels exhibited controlled IL-10 release, extended the duration of DC support, and protected DCs from inflammatory assault. After incorporation in PEG-IL10 hydrogels, these DCs induced CD25+FoxP3+ regulatory T cells (Tregs) during in vitro co-culture. These studies serve as a proof-of-concept for improving the efficacy of immunosuppressive cell therapies through biomaterial delivery. The flexible nature of this system enables its widespread application across a breadth of other tolerogenic applications for future investigation.
Databáze: OpenAIRE