Self-healing polysaccharide-based hydrogels as injectable carriers for neural stem cells.

Zhao Wei,Qiqing Zhang,Yong Mei Chen,Pengbo Zhang,Jingyi Zhao

doi:10.1038/srep37841

Abstract

Self-healing injectable hydrogels can be formulated as three-dimensional carriers for the treatment of neurological diseases with desirable advantages, such as avoiding the potential risks of cell loss during injection, protecting cells from the shearing force of injection. However, the demands for biocompatible self-healing injectable hydrogels to meet above requirements and to promote the differentiation of neural stem cells (NSCs) into neurons remain a challenge. Herein, we developed a biocompatible self-healing polysaccharide-based hydrogel system as a novel injectable carrier for the delivery of NSCs. N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) are the main backbones of the hydrogel networks, denoted as CEC-l-OSA hydrogel (“l” means “linked-by”). Owing to the dynamic imine cross-links formed by a Schiff reaction between amino groups on CEC and aldehyde groups on OSA, the hydrogel possesses the ability to self-heal into a integrity after being injected from needles under physiological conditions. The CEC-l-OSA hydrogel in which the stiffness mimicking nature brain tissues (100~1000 Pa) can be finely tuned to support the proliferation and neuronal differentiation of NSCs. The multi-functional, injectable, and self-healing CEC-l-OSA hydrogels hold great promises for NSC transplantation and further treatment of neurological diseases.

Highlights

Self-healing and injectable hydrogels can provide several advantages over the conventional injectable hydrogels in cell delivery[22,23], including: (i) avoiding the potential risks of cell loss during the injection, as well as providing necessary mechanical protections for the delivered cells from the shear damage during the injection[24,25]; (ii) confirming the morphologies and functionalities of the cells loaded inside the 3D microenvironment to control the quality of the loaded cells before transplantations; (iii) facilitating the fast mechanical recovery of the damaged hydrogels, keeping intrinsic functionalities and expanding the service life of implanted cell-loaded hydrogels[26,27,28]
Cell-loaded carboxyethyl chitosan (CEC)-l-oxidized sodium alginate (OSA) hydrogels were prepared in advance before the injection
CEC and OSA were dissolved into DMEM-12 (DF-12) culture medium separately, and the neural stem cells (NSCs) were suspended in the OSA component

Summary

Introduction

Self-healing and injectable hydrogels can provide several advantages over the conventional injectable hydrogels in cell delivery[22,23], including: (i) avoiding the potential risks of cell loss during the injection, as well as providing necessary mechanical protections for the delivered cells from the shear damage during the injection[24,25]; (ii) confirming the morphologies and functionalities of the cells loaded inside the 3D microenvironment to control the quality of the loaded cells before transplantations; (iii) facilitating the fast mechanical recovery of the damaged hydrogels, keeping intrinsic functionalities and expanding the service life of implanted cell-loaded hydrogels[26,27,28]. To assess the mechanical properties of the self-healing CEC-l-OSA hydrogels after injection, we performed the rheological measurements of the samples prepared in DF-12 culture medium (Cc = 0.02 g/mL) under 3 different conditions (Supplementary Fig. S5). To confirm the possibility of using the self-healing injectable hydrogels for nerve repair, the cytocompatibility, proliferation and differentiation of NSCs loaded inside the CEC-l-OSA hydrogels were examined and analyzed.

Results

Conclusion