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.
Highlights
A traumatic spinal cord injury (SCI) leads to permanent disability
Successful treatment of SCI remains an open issue and innovative approaches are required to improve patient’s quality of life. This is due to the complexity of the anatomy of the spinal cord and the cascade of events occurring at the damage site[3] that limits dramatically the treatment options which should be able to reduce glial scar formation as well as allow the neural regeneration integrating both neuroprotective and neuroregenerative cues[4]
In order to verify whether the presence of CS/β-GP hydrogel could alter the therapeutic efficacy of mesenchymal stem cells (MSCs), we evaluated their MV secretion, by analysing their presence within the supernatant
Summary
A traumatic spinal cord injury (SCI) leads to permanent disability. advances made in the understanding of the pathogenesis and improvements in early diagnosis and treatment, approximately 2.5 million people worldwide[1] live with the effects of SCI, which following functional deficits lead to disastrous social and human consequences and huge economic costs. When intervention occurs at the late phase, the process of glial scar formation has been already completed and axon regeneration and functional recovery become impossible far. Successful treatment of SCI remains an open issue and innovative approaches are required to improve patient’s quality of life. This is due to the complexity of the anatomy of the spinal cord and the cascade of events occurring at the damage site[3] that limits dramatically the treatment options which should be able to reduce glial scar formation as well as allow the neural regeneration integrating both neuroprotective and neuroregenerative cues[4]. The importance of scaffold anisotropic structure has been www.nature.com/scientificreports/
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