Periosteum plays a pivotal role in bone formation and reconstruction. The ideal repair process for critical-size bone defects with periosteum damage is to induce regeneration of periosteum tissue and the subsequent bone regeneration derived by the periosteum. Inspired by the bilayer structure of the natural periosteum, we develop a periosteum structure/function dual mimicking membrane for the in-situ restoration of periosteum and bone tissue. Among them, the macroporous fluffy guiding layer (TPF) simulates the fibrous layer of the natural periosteum, which is conducive to infiltration and oriented growth of fibroblasts. And the extracellular matrix (ECM)-like bioactive layer (TN) simulates the cambium layer of the natural periosteum, which significantly enhances the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs). A middle dense layer (PC) connects the above two layers and has the function of preventing the invasion of soft tissues while enhancing the biomimetic periosteum. In vivo restoration results show that the tri-layer biomimetic periosteum (TPF/PC/TN) has an outstanding effect in promoting the regeneration of both vascularized periosteum and bone at the same time. Therefore, the enhanced biomimetic periosteum developed in this research has a great clinical value in the efficient and high-quality reconstruction of critical-size bone defects with periosteum damage.
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