Highly Intrafibrillar‐Mineralized Scaffolds Engineered by Embedding ACP Seeds Into the Collagen Matrix via Shear‐Mediated Hydration‐Layer Modulation

Biological hard tissues such as bone form within a dynamic and hydrated microenvironment, where fluid shear stress (FSS) serves as an essential biomechanical stimulus during bone formation. A key structural basis of bone lies in intrafibrillarly mineralized collagen (IMC) fibrils, which endow bone with its unique mechanical properties. However, how FSS cooperates with interfacial hydration layers to regulate collagen mineralization remains unclear. Here, we introduce FSS into the synchronous self‐assembly/mineralization of collagen (SSM) model (Shear‐SSM) and demonstrate that FSS can significantly weaken the repulsive “hydration forces” arising from the hydration layers at the collagen‐ACP interface, thereby enhancing their interactions. This promotes the embedding of amorphous calcium phosphate (ACP) seeds into the self‐assembling collagen matrix via a bottom‐up route and leads to the formation of highly intrafibrillar‐mineralized collagen scaffolds (SMC) that achieve full mineralization comparable to that in natural bones. Furthermore, an in vivo rat mandibular defect repair experiment confirmed that SMC markedly enhances bone regeneration due to its improved biomimicry. These findings highlight the importance of interfacial hydration‐layer regulation in collagen mineralization, reveal a mechanistic contribution of biomechanical cues during bone formation, and provide a scalable strategy for engineering biomimetic bone‐repair materials.