Post-translational modification-regulating biomaterials for regeneration.

Abstract

Post-translational modification (PTM) refers to covalent chemical alterations occurring on proteins after their biosynthesis, encompassing phosphorylation, acetylation, ubiquitination and hundreds of other documented variants. These modifications act as dynamic molecular codes that precisely regulate protein subcellular localization, functional activity and interaction networks. Through core biological processes like signal transduction and metabolic regulation, they ultimately define cellular identity while maintaining adaptive responses to environmental stimuli. Emerging evidence links PTM dysregulation to various disease pathways, where impaired tissue regeneration emerges as a strategic intervention window for targeted PTM-based therapies. As core components of regenerative medicine, biomaterials with designable physicochemical properties can achieve precise PTM regulation through physicochemical signal transduction, overcoming conventional limitations and providing innovative platforms for tissue regeneration. This review analyzes how intrinsic material properties, surface modifications and ROS-regulating capabilities influence PTM control, while exploring the potential of biomaterials in precision PTM modulation. We then focus on advancements in bone, vascular, muscle and neural regeneration, demonstrating how biomaterial-mediated PTM regulation enables tissue-specific repair. Finally, we discuss current challenges and propose bioengineering strategies for advanced PTM control.