Supramolecular Hydrogels Based on Nanoclay and Guanidine-Rich Chitosan: Injectable and Moldable Osteoinductive Carriers

Supramolecular hydrogels have great potential as biomaterials for tissue engineering applications or vehicles for delivering therapeutic agents. Herein, a self-healing and pro-osteogenic hydrogel system is developed based on the self-assembly of laponite nanosheets and guanidinylated chitosan, where laponite works as a physical crosslinker with osteoinductive properties to form a network structure with a cationic guanidine group on chitosan chains. The hydrogels can be prepared with varying ratios of chitosan to laponite and display self-healing and injectable properties because of supramolecular forces as well as osteoinductive activity due to nanoclay. They enhance cell adhesion and promote osteogenic differentiation of mesenchymal stem cells by activating the Wnt/β-catenin signaling pathway. In addition, the hydrogel is used as a malleable carrier for the demineralized bone matrix (DBM). The loading of the DBM does not affect the self-healing and injectable natures of hydrogels while enhancing the osteogenic capacity, indicating that advanced allograft bone formulations with carriers can facilitate handling and bone healing. This work provides the first demonstration of therapeutic supramolecular design for the treatment of bone defects.