Oriented Cortical-Bone-Like Silk Protein Lamellae Effectively Repair Large Segmental Bone Defects in Pigs

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Orthopedic Engineering

Background:

• Repairing large bone defects in load-bearing sites remains a significant clinical challenge.
• Existing bone graft substitutes often lack the mechanical strength and biological cues for effective regeneration.
• Natural proteins offer potential for creating biocompatible and biodegradable bone scaffolds.

Purpose of the Study:

• To develop and evaluate silk fibroin (SF) based 3D scaffolds that mimic cortical bone structure for enhanced bone defect repair.
• To investigate the cellular response and bone regenerative capacity of these lamellar scaffolds in a large animal model.

Main Methods:

• Utilizing freeze-casting to assemble pure silk fibroin into 3D scaffolds with cortical-bone-like lamellae.
• Assessing scaffold properties including strength, biodegradability, and cellular interactions (mesenchymal stem cells, endothelial cells).
• Evaluating scaffold performance in repairing large segmental bone defects (LSBD) in minipigs, including neovascularization and bone formation.

Main Results:

• The lamellar SF scaffolds exhibited superior strength and promoted cell attachment, migration, and proliferation.
• High-SF-content lamellar scaffolds significantly enhanced bone regeneration compared to non-lamellar or low-SF controls.
• Scaffolds accelerated neovascularization by modulating macrophage phenotype and facilitated LSBD repair in minipigs within three months, without growth factors.
• Orienting lamellae parallel to the bone axis further improved regeneration.

Conclusions:

• Freeze-cast silk fibroin scaffolds with lamellar architecture can effectively mimic cortical bone properties.
• These biomimetic scaffolds promote significant bone regeneration and vascularization, offering a promising solution for LSBD.
• The ability to enhance bone repair using natural protein scaffolds without exogenous growth factors represents a significant advancement in regenerative medicine.