Mechanics‐Resilient HA/SIS‐Based Composite Scaffolds with ROS‐Scavenging and Bacteria‐Resistant Capacity to Address Infected Bone Regeneration

To address and regenerate infected bone defects complicated by issues such as inflammation and bone resorption, and to promote bone regeneration, this study focuses on the development of a composite scaffold with reactive oxygen species (ROS)‐scavenging and bacteria‐resistant properties. The composite scaffold integrates a self‐assembled small intestinal submucosa (SIS) hydrogel with pre‐adsorbed hydroxyapatite (HA) particles and tannic acid (TA), demonstrating distinctive mechanical resilience and porous structures, suitable for filling irregular cavities and facilitating cell infiltration, while exhibiting a broad‐spectrum of antibacterial efficacy and robust ROS‐scavenging capacity for tissue regeneration. RNA‐sequencing analysis indicates the underlying mechanism revealing the disrupting of arginine and alanine amino acid biosynthesis. Furthermore, the composite scaffold demonstrates excellent cytocompatibility, with cell viability exceeding 70%. Remarkably, it demonstrates exceptional anti‐inflammatory performances (≈5‐fold to the control). In an infected bone defect model, the composite scaffold facilitates superior bone regeneration, being ≈5‐fold greater than the control, while maintaining a conducive environment for cell adhesion and infiltration without scaffold collapse. This multifunctional composite scaffold emerges as a promising candidate for combating infections in bone regeneration, showcasing its potential in addressing complex bone‐related challenges. In this study, a mechanics‐resilient bone scaffolding materials are fabricated using small intestinal submucosa (SIS) based collagen and hydroxylapatite particles coated with tannic acid, which facilitates filling in the irregular bone defects and withstands external force to maintain porous structures for bone regeneration.