Advanced therapeutic scaffolds of biomimetic periosteum for functional bone regeneration.

Treating chronic bone injuries and defects remains a significant challenge in orthopedic medicine, impacting patient mobility, recovery time, and healthcare costs. The periosteum, a specialized, vascularized connective tissue covering the outer bone surface, plays a crucial role in osteogenesis and skeletal repair. While regenerating the periosteum is critical to restoring bone structure and function, current treatments face substantial limitations, including limited donor tissue availability, donor site complications, and the risk of immunological rejection. Recent advances in biomaterial engineering have driven the development of therapeutic platforms specifically designed to promote periosteal regeneration. These biomaterial-based platforms mimic the biochemical and biomechanical properties of the native periosteal microenvironment. By facilitating key cellular processes involved in osteogenesis and angiogenesis, these materials enable controlled spatiotemporal delivery of bioactive molecules, ion release, modulation of reactive oxygen species (ROS), and enhancement of pro-angiogenic factors. In this review, we discuss the recent advancements in engineered biomaterials, focusing on their mechanisms of action and applications in periosteum restoration. We also provide insights into current challenges and future research directions, emphasizing the critical role of these strategies in clinical practice. The perspectives offered here aim to guide the development of targeted, effective therapies for periosteum repair, ultimately advancing functional bone regeneration.