Affiliation:
1. School of Medicine Health Sciences Centre University College Dublin Belfield Dublin D04 V1W8 Ireland
2. UCD Conway Institute of Biomolecular & Biomedical Research University College Dublin Belfield Dublin D04 V1W8 Ireland
3. School of Chemistry University College Dublin Belfield Dublin D04 V1W8 Ireland
4. AO Research Institute Davos Clavadelerstrasse 8 Davos 7270 Switzerland
Abstract
AbstractSpinal cord injury (SCI) is a devastating condition with no curative therapy currently available. Immunomodulation can be applied as a therapeutic strategy to drive alternative immune cell activation and promote a proregenerative injury microenvironment. Locally injected hydrogels carrying immunotherapeutic cargo directly to injured tissue offer an encouraging treatment approach from an immunopharmacological perspective. Gelatin methacrylate (GelMA) hydrogels are promising in this regard, however, detailed analysis on the immunogenicity of GelMA in the specific context of the SCI microenvironment is lacking. Here, the immunogenicity of GelMA hydrogels formulated with a translationally relevant photoinitiator is analyzed in vitro and ex vivo. 3% (w/v) GelMA, synthesized from gelatin type‐A, is first identified as the optimal hydrogel formulation based on mechanical properties and cytocompatibility. Additionally, 3% GelMA‐A does not alter the expression profile of key polarization markers in BV2 microglia or RAW264.7 macrophages after 48 h. Finally, it is shown for the first time that 3% GelMA‐A can support the ex vivo culture of primary murine organotypic spinal cord slices for 14 days with no direct effect on glial fibrillary acidic protein (GFAP+) astrocyte or ionized calcium‐binding adaptor molecule 1 (Iba‐1+) microglia reactivity. This provides evidence that GelMA hydrogels can act as an immunotherapeutic hydrogel‐based platform for preclinical SCI.
Funder
University College Dublin
Science Foundation Ireland
Horizon 2020 Framework Programme
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
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