Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment

Abstract

Advanced therapies which combine cells with biomaterial-based carriers are recognized as an emerging and powerful method to treat challenging diseases, such as spinal cord injury (SCI). By enhancing transplanted cell survival and grafting, biomimetic hydrogels can be properly engineered to encapsulate cells and locate them at the injured site in a minimally invasive way. In this work, chitosan (CS) based hydrogels were developed to host mesenchymal stem cells (MSCs), since their paracrine action can therapeutically enhance the SC regeneration, limiting the formation of a glial scar and reducing cell death at the injured site. An injectable and highly permeable CS-based hydrogel was fabricated having a rapid gelation upon temperature increase from 0 to 37 °C. CS was selected as former material both for its high biocompatibility that guarantees the proper environment for MSCs survival and for its ability to provide anti-inflammatory and anti-oxidant cues. MSCs were mixed with the hydrogel solution prior to gelation. MSC viability was not affected by the CS hydrogel and encapsulated MSCs were able to release MSC-vesicles as well as to maintain their anti-oxidant features. Finally, preliminary in vivo tests on SCI mice revealed good handling of the CS solution loading MSCs during implantation and high encapsulated MSCs survival after 7 days.

Role of the CXCR4-SDF1-HMGB1 pathway in the directional migration of cells and regeneration of affected organs

“…Among the different tools of regenerative medicine “stem cells” are considered the most promising due to their self-renewal capability and multi-differentiation potential. However, recent studies have shown that the positive outcomes of different types of stem cell-based regenerative therapies are not directly correlated to the engraftment of transplanted cells[ 2 , 3 ]. These findings have created a huge interest in the regenerative potential of paracrine factors and have led scientists to reveal the regenerative potential of proteins in the secretomes.…”

Natural-Based Biomaterials for Peripheral Nerve Injury Repair

“…Moreover, it is a re-absorbable biomaterial whose degradation products (including chito-oligosaccharides) positively influence nerve regeneration ( Gong et al, 2009 ; Zhao et al, 2017 ). Furthermore, chitosan can be processed through many fabrication technologies ( Ruini et al, 2015 ; Tonda-Turo et al, 2017b ) to produce NGCs both as external wall material and cell-based therapies as internal filler ( Boido et al, 2019 ; Tonda-Turo et al, 2020 ). One factor limiting chitosan use as a nerve guide is its low mechanical strength; nevertheless, Freier et al (2005b) demonstrated that modifying the chitosan acetylation degree, its mechanical stability can be improved and conduits with different acetylation degree were also tested in vivo ( Haastert-Talini et al, 2013 ).…”

Polymer-Based Scaffold Strategies for Spinal Cord Repair and Regeneration

“…Chitosan is a kind of positively charged biopolymer compound rarely seen in nature. It has abundant sources, low price, non-toxicity, non-irritation, non-antigenicity, heat-source reaction, non-hemolysis, non-mutagenicity, natural degradation, good histocompatibility, and controlled-release effects ( Boido et al, 2019 ). In addition, during the treatment of SCI, chitosan has significant neuroprotective properties, maintains the integrity of the cell membrane, and can block the activity of lipid peroxidation ( Elizalde-Peña et al, 2017 ).…”