Long-Term Bone Regeneration Enabled by a Polyhedral Oligomeric Silsesquioxane (POSS)-Enhanced Biodegradable Hydrogel

The development of artificial bone substitutes mimicking the extracellular matrix is a promising strategy for bone repair and regeneration. However, the preparation of materials tailored to feature sufficient mechanical properties, appropriate degradation rates, and favorable osteoinductivity continues to be a great challenge. Hydrogels from biopolymers have emerged as viable substitutes in bone regeneration, but they often suffer from insufficient mechanical strength and rapid degradation rate, critically limiting their clinical applicability. Here, we demonstrate that inorganic/biopolymer hybrid hydrogels formed through photo-cross-linking of methacrylated gelatin (Gel) and octamethacrylated polyhedral oligomeric silsesquioxane (OMAPOSS) nanocages can be tailored to possess high mechanical strength, more appropriate degradation rate, and provide biological activity to meet tissue growth demands outperforming simple Gel hydrogels without POSS. Moreover, Gel-POSS hybrid hydrogels effectively promote mesenchymal stem cell (MSC) attachment, spreading, and proliferation, and, critically enhance the osteogenesis of MSCs as evidenced by improved bone repair in a rat calvarial defect model. Hence, such POSS-enhanced synthetically tailored hybrid hydrogels represent a promising concept for long-term bone tissue regeneration.