Advanced bio-polymers for bone regeneration: Harnessing anti-inflammatory, oxidative stress, and pro-angiogenic strategies

Bone defects resulting from trauma, tumor resection, or infection constitute significant clinical challenges in orthopedics, frequently causing compromised healing and elevated complication rates. While inflammatory responses and reactive oxygen species (ROS) are essential for initiating bone repair, their excessive persistence disrupts osteoblast-osteoclast homeostasis, suppresses angiogenesis, and ultimately impedes osseous regeneration. Conventional treatments, including autografts, allografts, and synthetic materials (bioceramics/metals), exhibit limitations in biocompatibility, donor availability, and dynamic responsiveness to pathophysiological demands. Innovative polymer-based biomaterials integrating anti-inflammatory, ROS-neutralizing, and angiogenic functions enable precise spatiotemporal modulation of bone microenvironments through synergistic immunoregulation, vascular network formation, and osteogenic differentiation.This review examines the bone healing process and identifies bioactivators targeting key signaling pathways, including pharmaceuticals, metal ions, growth factors, and exosomes. We highlight advancements in multifunctional polymeric scaffolds, such as stimuli-responsive hydrogels, 3D-printed structures, and nanocomposite networks, which mimic the mechanical properties of the native extracellular matrix (ECM) and enable controlled delivery of bioactivators. Furthermore, we discuss recent progress and challenges in clinical translation, including large-scale production, sterilization techniques, and regulatory barriers. This review aims to provide researchers and clinicians with comprehensive insights to advance the development of next-generation polymers for bone regeneration.