The periosteum orchestrates the microenvironment of bone regeneration, including facilitating local neuro-vascularization and regulating immune responses. To mimic the role of natural periosteum for bone repair enhancement, we adopted the principle of biomimetic mineralization to delicately inlay amorphous cerium oxide within eggshell membranes (ESMs) for the first time. Cerium from cerium oxide possesses unique ability to switch its oxidation state from cerium III to cerium IV and vice versa, which provides itself promising potential for biomedical applications. ESMs are mineralized with cerium­(III, IV) oxide and examined for their biocompatibility. Apart from serving as physical barriers, periosteum-like cerium­(III, IV) oxide-mineralized ESMs are biocompatible and can actively regulate immune responses and facilitate local neuro-vascularization along with early-stage bone regeneration in a murine cranial defect model. During the healing process, cerium-inlayed biomimetic periosteum can boost early osteoclastic differentiation of macrophage lineage cells, which may be the dominant mediator of the local repair microenvironment. The present work provides novel insights into expanding the definition and function of a biomimetic periosteum to boost early-stage bone repair and optimize long-term repair with robust neuro-vascularization. This new treatment strategy which employs multifunctional bone-and-periosteum-mimicking systems creates a highly concerted microenvironment to expedite bone regeneration.

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Nanohydroxyapatite (nHAP) has broad applications because of its nanoscopical dimension, large specific surface area, biocompatibility, and low cytotoxicity. Researchers recently discovered that nHAP synthesized in vitro inhibits the growth of different types of tumor cells. Nanohydroxyapatite with potent drug adsorption and loading capacity has potential applications in tumor diagnosis and treatment. Because local tumors and areas of tumor metastasis also produce pathological nHAP in vivo to promote progression and invasion, the role of nHAP in tumorigenesis and development is perceived literature by many as Janus, the double‐faced deity in ancient Roman mythology. In the present review, two types of nHAP (those synthesized in vitro and those produced in vivo) that are affiliated with tumors, their mechanisms in tumor progression as well as their applications in tumor treatment are elucidated to create a backdrop for future research in this exciting, yet controversial arena.

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