Periosteum Organoid: Biomimetic Design Inspired From the Bone Healing Process

ABSTRACT Large bone defects present major problems in plastic, maxillofacial, and orthopedic reconstructive surgery. With respect to osseous tissues, currently, autologous and allogeneic bone grafts are commonly used clinical treatments, but there are limitations in terms of donor availability, morbidity, and risk of immunogenic reactions. Tissue‐engineered bone constructs offer promising alternatives but struggle to replicate the complex biological functions of native bone, leading to suboptimal outcomes. The periosteum has been shown to be a key factor in bone regeneration and has a bilayered structure that is essential for bone integrity and repair. However, large bone defects cause damage to the periosteum and weaken its regenerative capacity. Therefore, periosteum organoids have been developed with the help of new organoid technology to achieve accelerated bone regeneration. This technology incorporates a variety of natural/synthetic materials and biologically derived factors that can be endowed with key biological functions for bone regeneration, such as, antimicrobial, immunomodulatory, neuromodulatory, angiogenic, and osteogenic capabilities. This review explores the structure and function of periosteum, the design and application of periosteum organoids and their potential integration with bone organoids. In addition, the recent advances and future directions for the use of such organoids in novel regenerative medicine and bone repair strategies are highlighted.