A mechanically adaptive “all-sugar” hydrogel for cell-laden injection

Abstract

Injectable hydrogels possess strict requirements of network structure and biocompatibility for cell therapy. It is highly required to load and deliver cells with no damage during the injection operation and accelerate their proliferation after injection at the lesions. Herein, naturally derived chitosan (CS) and hyaluronic acid (HA) were chemically modified to synthesize methylacrylylated chitosan (CSMA) and aldehyde-containing hyaluronic acid (OHA). The imine cross-linkage can be rapidly constructed and reversibly broken between amino and aldehyde groups, endowing the resulting hydrogel with highly efficient mechanical adaptivity, including shearing-thinning and fast self-healing. Besides, the methacrylate groups of CSMA can be cross-linked by photoinitiation, making the dynamic hydrogel with adjustable elasticity and modulus to match the cell culture. The dynamic crosslinked hydrogel demonstrated good compatibility with a wide variety of body cells and bone marrow mesenchymal stem cells (BMSCs). Benefiting from the excellent mechanical adaptivity and cytocompatibility, BMSCs were in situ encapsulated in the dynamic hydrogel and then extruded through a clinically used syringe. Remarkably, the percentage of living cells still reached 87.6% after injection, with no significant cell damage compared with their original state before injection. Moreover, the osteogenic and chondrogenic differentiation abilities of stem cells were not affected by the extrusion injection due to the mechanically adaptive three-dimensional network of the dynamic hydrogel. Taken together, the proposed mechanically adaptive “all-sugar” hydrogels intensify the cell-laden injectability and enhance the long-term viability of cell culture, which shows great potential in the field of cell therapy and tissue engineering.