Mn-based methacrylated gellan gum hydrogels for MRI-guided cell delivery and imaging

This work aims to engineer a new stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. To enable the hydrogel visualization under Magnetic Resonance Imaging (MRI), GG-MA solutions were supplemented with paramagn...

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Published in:Bioengineering (Basel) 2023-03, Vol.10 (4), p.1-16
Main Authors: Vieira, Sílvia, Strymecka, Paulina, Stanaszek, Luiza, Silva-Correia, Joana, Drela, Katarzyna, Fiedorowicz, Michał, Malysz-Cymborska, Izabela, Janowski, Miroslaw, Reis, R. L., Lukomska, Barbara, Walczak, Piotr, Oliveira, Joaquim M.
Format: Article
Language:English
Subjects:
Bioengineering
Biomedical materials
Cell culture
Cell delivery
Central nervous system
Cerebrospinal fluid
Colloids
Crosslinking
Gellan Gum
Hydrogels
In vivo methods and tests
Injectable hydrogels
Magnetic resonance imaging
Manganese
Manganese ions
Production processes
RAG2 protein
Science & Technology
Spinal cord
Stem cells
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Summary:This work aims to engineer a new stable injectable Mn-based methacrylated gellan gum (Mn/GG-MA) hydrogel for real-time monitored cell delivery into the central nervous system. To enable the hydrogel visualization under Magnetic Resonance Imaging (MRI), GG-MA solutions were supplemented with paramagnetic Mn2+ ions before its ionic crosslink with artificial cerebrospinal fluid (aCSF). The resulting formulations were stable, detectable by T1-weighted MRI scans and also injectable. Cell-laden hydrogels were prepared using the Mn/GG-MA formulations, extruded into aCSF for crosslink, and after 7 days of culture, the encapsulated human adipose-derived stem cells remained viable, as assessed by Live/Dead assay. In vivo tests, using double mutant MBPshi/shi/rag2 immunocompromised mice, showed that the injection of Mn/GG-MA solutions resulted in a continuous and traceable hydrogel, visible on MRI scans. Summing up, the developed formulations are suitable for both non-invasive cell delivery techniques and image-guided neurointerventions, paving the way for new therapeutic procedures. Sílvia Vieira acknowledges the FCT Ph.D. scholarship (SFRH/BD/102710/2014). J. Miguel Oliveira and J. Silva-Correia acknowledge the FCT grants under the Investigator FCT program (IF/01285/2015 and IF/00115/2015, respectively). The authors also acknowledge the funds provided under the project NanoTech4ALS, funded under the EU FP7 M-ERA.NET program, and ESF (POWR.03.02.00-00-I028/17-00).
ISSN:2306-5354
2306-5354
DOI:10.3390/bioengineering10040427