Mechanism-Guided Nanoengineered Peptides Overcome Bone Healing Bottlenecks via Spatiotemporal Control

Bone healing is a complex process often compromised by breakdowns in coordinated biological events like inflammatory resolution, vascular invasion, and matrix mineralization. While therapeutic peptides offer diverse functions for bone repair, including immunomodulation and osteogenic signaling, their clinical utility is hampered by rapid degradation, poor local retention, and inadequate spatiotemporal presentation. This review addresses how nanoengineering can overcome these limitations, transforming peptide sequence information into effective, localized signals for regenerative potential, particularly in complex defects where single-factor approaches fall short.

The authors conducted a comprehensive review, organizing existing literature on nanoengineered therapeutic peptides for bone healing based on a mechanism-guided framework. This approach systematically examines how nanoengineering addresses sequential biological bottlenecks, including immuno-osteogenesis, angiogenic-osteogenic coupling, mineralization guidance, and endogenous cell recruitment. The review critically analyzes how peptide sequence features encode regenerative potential and how nanoscale presentation dictates biological effectiveness, contrasting with previous reviews typically organized by material platform (e.g., hydrogels, scaffolds) or peptide category (e.g., biomimetic, antimicrobial).