Endogenous Metal Ion-Enriched Immunostimulating Biomimetic Scaffold Improves In Situ Bone Regeneration.

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Immunology

Background:

• Large-scale bone defects pose significant clinical challenges for regeneration.
• Endogenous metal ions are crucial for bone remodeling and immune response, but their precise regulation is lacking.
• Existing biomaterials often fail to effectively harness these endogenous factors for enhanced healing.

Purpose of the Study:

• To develop a novel biomimetic scaffold capable of capturing and utilizing endogenous metal ions.
• To investigate the scaffold's ability to modulate immune responses for improved bone regeneration.
• To establish a clinically applicable strategy for repairing critical-sized bone defects.

Main Methods:

• Fabrication of an endogenous metal ion-enriched immunostimulation-amplified bone biomimetic scaffold (emia-BBS) using nano-hydroxyapatites, collagen fibrils, and mussel adhesion proteins.
• Evaluation of the scaffold's ability to mimic native bone nanostructure and mechanical properties.
• In vivo assessment of the emia-BBS in large-scale mandibular defects, analyzing macrophage recruitment/reprogramming and skeletal stem cell activation.

Main Results:

• The emia-BBS successfully mimicked native bone and efficiently captured endogenous metal ions.
• Scaffold-induced metal ion enrichment promoted macrophage recruitment and M2 polarization, enhancing innate immunity.
• M2 macrophages facilitated skeletal stem cell recruitment and osteogenic activation via the CCL5/CCR5/STAT3 signaling pathway.

Conclusions:

• The developed emia-BBS provides a novel immunomodulatory strategy for bone regeneration.
• Harnessing endogenous ion dynamics offers a precise and amplified approach to stimulate regenerative signals.
• This method presents a clinically applicable solution for critical-sized bone defect repair.