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

• Published in: Advanced materials (Weinheim) Vol. 37; no. 10; pp. e2414543 - n/a
• Main Authors: Shuai, Yajun, Yang, Tao, Zheng, Meidan, Zheng, Li, Wang, Jie, Mao, Chuanbin, Yang, Mingying
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2025; John Wiley and Sons Inc
• Subjects: Animals; bio‐manufacturing; Bone Regeneration - drug effects; bone tissue regeneration; Cell Proliferation - drug effects; Cortical Bone; cortical bone organoids; Defects; Endothelial cells; Fibroins - chemistry; freeze‐casting; Growth factors; Human Umbilical Vein Endothelial Cells - cytology; Humans; Lamellar structure; Macrophages; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Osteoblasts - cytology; Proteins; Regeneration (physiology); Scaffolds; Silk; Silk fibroin; Stem cells; Swine; Swine, Miniature; Tissue Scaffolds - chemistry; bone tissue regeneration; bio‐manufacturing; freeze‐casting; cortical bone organoids; silk fibroin
• ISSN: 0935-9648; 1521-4095; 1521-4095
• DOI: 10.1002/adma.202414543

Assembling natural proteins into large, strong, bone‐mimetic scaffolds for repairing bone defects in large‐animal load‐bearing sites remain elusive. Here this challenge is tackled by assembling pure silk fibroin (SF) into 3D scaffolds with cortical‐bone‐like lamellae, superior strength, and biodegradability through freeze‐casting. The unique lamellae promote the attachment, migration, and proliferation of tissue‐regenerative cells (e.g., mesenchymal stem cells [MSCs] and human umbilical vein endothelial cells) around them, and are capable of developing in vitro into cortical‐bone organoids with a high number of MSC‐derived osteoblasts. High‐SF‐content lamellar scaffolds, regardless of MSC inoculation, regenerated more bone than non‐lamellar or low‐SF‐content lamellar scaffolds. They accelerated neovascularization by transforming macrophages from M1 to M2 phenotype, promoting bone regeneration to repair large segmental bone defects (LSBD) in minipigs within three months, even without growth factor supplements. The bone regeneration can be further enhanced by controlling the orientation of the lamella to be parallel to the long axis of bone during implantation. This work demonstrates the power of oriented lamellar bone‐like protein scaffolds in repairing LSBD in large animal models. Silk proteins can be fabricated into large scaffolds with cortical‐bone‐like lamellar structures through freeze‐casting. The resultant freeze‐cast scaffolds are made of parallel silk protein lamellae and can be implanted into pig models to achieve effective bone regeneration without side effects.