Injectable and In Situ Hydration‐Reinforced Hybrid Bone Cements for Accelerated Bone Regeneration

To enable minimally invasive bone defect repair, an injectable and hydration‐reinforced bone cement (L‐PEGS/CPC) is designed through biomimetic reconstruction. The hydrophilic L‐PEGS organic phase provides abundant nucleation sites, synergizing with its porous architecture to accelerate CPC hydration, thereby endowing the composite with exceptional mechanical strength and fatigue resistance—offering a novel strategy for clinical bone repair materials. Abstract Injectable bone cements are recognized as ideal solution for bone augmentation due to their minimally invasive introduction strategy. However, current clinical formulations and composites, while demonstrating improvements in certain areas, often fail to comprehensively address challenges, including rheological injectability, mechanical stability, interconnected porosity, degradability, and bioactivity. To overcome limitations, a novel bone cement comprising linear polyhydroxy PEGylated poly(glycerol sebacate) (L‐PEGS) and calcium phosphate cement (CPC) is developed. The incorporation of L‐PEGS enhances injectability and reinforces the mechanical weakness of CPC, resulting in improvement in compressive strength (increased by 16.7 folds) and fatigue resistance (1000 cycles). Owing to linear polyhydroxy backbone, L‐PEGS initiates self‐reinforcing cross‐linking reaction synchronized with the hydration of CPC into hydroxyapatite. This hydration reinforcement is mediated by its abundant hydroxyl groups and high water absorption capacity, which accelerate hydration kinetics. Concurrently, the cross‐linking reaction generates in situ carbon dioxide, resulting in porous microarchitecture that facilitates hydration process, enhances cement degradability, and promotes nutrient exchange and new bone ingrowth. In vitro and vivo studies confirmed that L‐PEGS/CPC substantially enhances osteogenesis compared to clinical materials. Collectively, this injectable, hydration‐driven, and self‐reinforcing bone cement offers comprehensive solution to the challenges in current bone graft materials, holding promise for clinical bone repair. To enable minimally invasive bone defect repair, an injectable and hydration-reinforced bone cement (L-PEGS/CPC) is designed through biomimetic reconstruction. The hydrophilic L-PEGS organic phase provides abundant nucleation sites, synergizing with its porous architecture to accelerate CPC hydration, thereby endowing the composite with exceptional mechanical strength and fatigue resistance—offering a novel strategy for clinical bone repair materials. Abstract Injectable bone cements are recognized as ideal solution for bone augmentation due to their minimally invasive introduction strategy. However, current clinical formulations and composites, while demonstrating improvements in certain areas, often fail to comprehensively address challenges, including rheological injectability, mechanical stability, interconnected porosity, degradability, and bioactivity. To overcome limitations, a novel bone cement comprising linear polyhydroxy PEGylated poly(glycerol sebacate) (L-PEGS) and calcium phosphate cement (CPC) is developed. The incorporation of L-PEGS enhances injectability and reinforces the mechanical weakness of CPC, resulting in improvement in compressive strength (increased by 16.7 folds) and fatigue resistance (1000 cycles). Owing to linear polyhydroxy backbone, L-PEGS initiates self-reinforcing cross-linking reaction synchronized with the hydration of CPC into hydroxyapatite. This hydration reinforcement is mediated by its abundant hydroxyl groups and high water absorption capacity, which accelerate hydration kinetics. Concurrently, the cross-linking reaction generates in situ carbon dioxide, resulting in porous microarchitecture that facilitates hydration process, enhances cement degradability, and promotes nutrient exchange and new bone ingrowth. In vitro and vivo studies confirmed that L-PEGS/CPC substantially enhances osteogenesis compared to clinical materials. Collectively, this injectable, hydration-driven, and self-reinforcing bone cement offers comprehensive solution to the challenges in current bone graft materials, holding promise for clinical bone repair. Advanced Science, EarlyView.