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TitleInduction of neurite outgrowth in 3D hydrogel-based environments
Author(s)Silva, Rita Catarina Assunção Ribeiro
Oliveira, Cátia Andreia Costa
Ziv-Polat, Ofra
Gomes, Eduardo Domingos Correia
Sahar, Abraham
Sousa, Nuno
Silva, Nuno A.
Salgado, A. J.
Keywordsgellan-gum hydrogels
adipose tissue-derived stem cells
glial-cell line derived neurotrophic factor
iron oxide nanoparticles
peripheral nerve repair
Issue date20-Oct-2015
PublisherIOP Publishing
JournalBiomedical Materials
CitationAssunção-Silva, R. C., Oliveira, C. C., Ziv-Polat, O., et. al. (2015). Induction of neurite outgrowth in 3D hydrogel-based environments. Biomedical Materials, 10(5), 051001
Abstract(s)The ability of peripheral nervous system (PNS) axons to regenerate and re-innervate their targets after an injury has been widely recognized. However, despite the considerable advances made in microsurgical techniques, complete functional recovery is rarely achieved, especially for severe peripheral nerve injuries (PNIs). Therefore, alternative therapies that can successfully repair peripheral nerves are still essential. In recent years the use of biodegradable hydrogels enriched with growth-supporting and guidance cues, cell transplantation, and biomolecular therapies have been explored for the treatment of PNIs. Bearing this in mind, the aim of this study was to assess whether Gly-Arg-Gly-Asp-Ser synthetic peptide (GRGDS)-modified gellan gum (GG) based hydrogels could foster an amenable environment for neurite/axonal growth. Additionally, strategies to further improve the rate of neurite outgrowth were also tested, namely the use of adipose tissue derived stem cells (ASCs), as well as the glial derived neurotrophic factor (GDNF). In order to increase its stability and enhance its bioactivity, the GDNF was conjugated covalently to iron oxide nanoparticles (IONPs). The impact of hydrogel modification as well as the effect of the GDNF-IONPs on ASC behavior was also screened. The results revealed that the GRGDS-GG hydrogel was able to support dorsal root ganglia (DRG)-based neurite outgrowth, which was not observed for non-modified hydrogels. Moreover, the modified hydrogels were also able to support ASCs attachment. In contrast, the presence of the GDNF-IONPs had no positive or negative impact on ASC behavior. Further experiments revealed that the presence of ASCs in the hydrogel improved axonal growth. On the other hand, GDNF-IONPs alone or combined with ASCs significantly increased neurite outgrowth from DRGs, suggesting a beneficial role of the proposed strategy for future applications in PNI regenerative medicine
Publisher version
AccessOpen access
Appears in Collections:ICVS - Artigos em revistas internacionais / Papers in international journals

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