Revolutionizing Bone Repair and Regeneration: The Role of Machine Learning in Designing Advanced Nanocomposite Hydrogels

ABSTRACT Bone repair is a complex biological process requiring dynamic interplay between cellular mechanisms, molecular signaling, and environmental factors. The intricate stages of bone healing, including hematoma formation, inflammation, soft callus development, and hard callus remodeling, are driven by coordinated cellular responses and molecular pathways. Proinflammatory cytokines, growth factors, and the extracellular matrix play critical roles in promoting osteogenesis and angiogenesis. Factors such as age, systemic health, and mechanical stability significantly influence repair efficiency. To address limitations in natural healing, advancements in regenerative medicine have introduced innovative materials like nanocomposite hydrogels, which mimic the natural bone microenvironment and enhance cellular function. Semi‐interpenetrating network (semi‐IPN) hydrogels have emerged as a promising tool for bone tissue engineering. Combining crosslinked and non‐crosslinked polymers, these hydrogels offer a balance of mechanical stability, biological functionality, and controlled degradation. Semi‐IPN hydrogels provide structural support, facilitate cell attachment, and enable the sustained release of bioactive molecules. Their flexibility and adaptability make them suitable for encapsulating stem cells and promoting targeted bone regeneration. Moreover, nonsurgical and surgical scaffold delivery methods, ranging from injectable hydrogels to 3D‐printed and magnetically guided scaffolds, have expanded the horizons of bone repair strategies, reduced invasiveness, and improved patient outcomes. This review explores the dynamics of bone healing, the role of hydrogels in promoting regeneration, and the advanced construction strategies of semi‐IPN hydrogels for bone repair. By integrating polymer science, nanotechnology, and bioengineering, semi‐IPN hydrogels represent a transformative shift in addressing bone defects, paving the way for innovative therapeutic approaches in regenerative medicine. With ongoing advancements, these technologies hold significant potential to improve the effectiveness and accessibility of bone repair solutions.