Synthesis of a tri-network alginate hydrogel for use as an injectable cell carrier

Abstract

Abstract Injectable hydrogels are promising biomaterials due to their permeability and biocompatibility and are advantageous for minimally-invasive surgical procedures to administer bioactive agents, including viable cells. Current injectable hydrogels have a single input/stimulus for crosslinking and utilize potentially toxic ultraviolet radiation. A tri-stimuli-responsive alginate-based injectable hydrogel was developed and incorporated: (1) supramolecular complex formation between β -cyclodextrin conjugated alginate and thermo-responsive tri-block Pluronic® copolymers; (2) visible light crosslinking via acrylate conjugation; and (3) ionic crosslinking of the alginate backbone via exposure to calcium chloride. The tri-crosslinking system allows the end-user to control the final physico-mechanical properties of the hydrogel using different external stimuli, applicable for a variety of soft tissue repair. The mechanical properties, specifically the storage moduli of the viscoelastic hydrogels, were tuned up to 35 kPa at body temperature using multiple crosslinking approaches in succession. Human mesenchymal stem cells (MSCs) were suspended in modified-alginate solutions, with and without Pluronic® copolymers, ejected from a syringe, and crosslinked via visible light and divalent salt exposure, to form three-dimensional hydrogel networks. Encapsulated MSCs remained viable during material processing and post 48 h of in vitro culture. The tri-crosslinked alginate hydrogels show efficacy as an MSC carrier for injectable delivery.