An In Vitro and Ex Vivo Analysis of the Potential of GelMA Hydrogels as a Therapeutic Platform for Preclinical Spinal Cord Injury.

Autor: Walsh CM; School of Medicine, Health Sciences Centre, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland.; UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland., Wychowaniec JK; School of Chemistry, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland.; AO Research Institute Davos, Clavadelerstrasse 8, Davos, 7270, Switzerland., Costello L; School of Medicine, Health Sciences Centre, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland., Brougham DF; School of Chemistry, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland., Dooley D; School of Medicine, Health Sciences Centre, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland.; UCD Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin, D04 V1W8, Ireland.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2023 Oct; Vol. 12 (26), pp. e2300951. Date of Electronic Publication: 2023 May 12.
DOI: 10.1002/adhm.202300951
Abstrakt: Spinal 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.
(© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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