LAUSR

Guided bone regeneration (GBR) has emerged as the most prevalent therapeutic approach for alveolar bone augmentation. However, current GBR membranes struggle to balance mechanical strength, space‐maintaining capacity, osteogenic activity, and biodegradability. Nature offers elegant solutions to real‐world problems. Herein, a crab cuticle‐derived bilayer GBR membrane (PDM), comprising exocuticle and endocuticle, is engineered through simple pretreatment and partially demineralization. PDM demonstrates exceptional plasticity and shape retention, maintaining a tensile strength of 23.4 MPa even in humid environments, far surpassing that of commercial absorbable membranes. This is likely attributed to the mechanical enhancement associated with Bouligand structure and remaining minerals in PDM. The smooth and dense endocuticle surface effectively inhibited fibroblast invasion, while the rough, amorphous calcium carbonate (ACC)‐rich exocuticle layer potently stimulated stem cell osteogenic differentiation, leading to significantly enhanced mineralization. Remarkably, in vivo, PDM guided the complete regeneration of critical‐sized bone defects with vascularized new bone tissue. Transcriptomic analysis unraveled protein networks associated with cell‐matrix reactions, extracellular matrix formation, bone formation, and angiogenesis, clarifying the complex molecular interactions and signal cascades mediated by PDM. This work establishes a straightforward yet powerful paradigm for developing next‐generation biomaterials by integrating structural maintenance and bioactive properties within natural hierarchical architectures.