An engineered lamellar bone mimicking full-scale hierarchical architecture for bone regeneration

Area of Science:

• Biomaterials Engineering
• Tissue Engineering
• Skeletal Biology

Background:

• Lamellar bone, mature bone's structural motif, features 6 hierarchical scales crucial for physiological behavior and osteogenic bioactivity.
• Replicating the full-scale hierarchy of lamellar bone in engineered constructs presents a significant challenge.

Purpose of the Study:

• To engineer compact constructs that mimic the full-scale hierarchy of lamellar bone.
• To investigate the effects of mineralization on the physicochemical properties and bioactivities of bioskived collagen matrices.
• To elucidate the hierarchical mimicry and hierarchy-property relationships in engineered bone constructs.

Main Methods:

• Fabrication of multi-sheeted collagen matrices using bioskiving.
• Systematic investigation of mineralization effects on matrix properties and bioactivities.
• Bioinformatic analysis to identify activated signaling pathways.

Main Results:

• Mineralization duration influenced hierarchical mimicry and osteogenic bioactivity in a bidirectional manner (increase then decrease).
• Constructs mineralized for 9 days accurately mimicked all hierarchical scales and enhanced osteogenesis.
• The 9-day mineralized construct activated the integrin α5-PI3K/AKT signaling pathway, facilitating critical-sized bone defect repair.

Conclusions:

• A bioinspired strategy was developed to fully replicate the complex hierarchy of compact mineralized tissue.
• The 9-day mineralized construct serves as a valuable model for studying bone structure-function relationships.
• This approach holds potential for regenerative medicine applications in bone repair.