Hydrogel microspheres for bone regeneration through regulation of the regenerative microenvironment

Bone defects are a prevalent category of skeletal tissue disorders in clinical practice, with a range of pathogenic factors and frequently suboptimal clinical treatment effects. In bone regeneration of bone defects, the bone regeneration microenvironment-composed of physiological, chemical, and physical components-is the core element that dynamically coordinates to promote bone regeneration. In recent years, medical biomaterials with bioactivity and functional tunability have been widely researched upon and applied in the fields of tissue replacement/regeneration, and remodelling of organ structure and function. The biomaterial treatment system based on the comprehensive regulation strategy of bone regeneration microenvironment is expected to solve the clinical problem of bone defect. Hydrogel microspheres (HMS) possess a highly specific surface area and porosity, an easily adjustable physical structure, and high encapsulation efficiency for drugs and stem cells. They can serve as highly efficient carriers for bioactive factors, gene agents, and stem cells, showing potential advantages in the comprehensive regulation of bone regeneration microenvironment to enhance bone regeneration. This review aims to clarify the components of the bone regeneration microenvironment, the application of HMS in bone regeneration, and the associated mechanisms. It also discusses various preparation materials and methods of HMS and their applications in bone tissue engineering. Furthermore, it elaborates on the relevant mechanisms by which HMS regulates the physiological, chemical, and physical microenvironment in bone regeneration to achieve bone regeneration. Finally, we discuss the future prospects of the HMS system application for comprehensive regulation of bone regeneration microenvironment, to provide novel perspectives for the research and application of HMS in the bone tissue engineering field.