Engineered self-assembling hydrogel systems for advanced guided bone regeneration: structural optimization and biofunctional modulation.

Self-assembling hydrogels have emerged as a promising class of biomaterials for bone regeneration due to their highly tunable properties, stimulus responsiveness, and excellent biocompatibility. While current research predominantly focuses on their applications as structural scaffolds or conventional drug delivery systems, recent advancements highlight their potential for spatiotemporal regulation of bone repair through advanced morphological engineering and multifunctional module integration. This review synthesizes recent progress in self-assembling hydrogel-based strategies aimed at enhancing bone regeneration, emphasizing their dual roles as bioresponsive carriers and architectural regulators. Particular emphasis is placed on their capacity for controlled release of bioactive agents and dynamic adaptation to microenvironmental stimuli, particularly when implementing synergistic design principles combining structural optimization with functional multiplexing. The interplay between these modalities within three-dimensional spatial contexts is systematically analyzed, revealing critical synergies that potentiate osteogenic outcomes. Finally, unresolved challenges related to degradation kinetics, vascularization induction, and precise spatiotemporal control are critically evaluated, along with proposed solutions to advance clinical translation. These collective insights underscore the transformative potential of self-assembling hydrogels in addressing the complexities of critical-sized bone defect regeneration while identifying key directions for future investigative efforts.