Kim Jeong In, Kieu Thi Thu Trang, Lee Jeong-Chae
Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13488, South Korea.
Department of Bioactive Material Sciences, Research Center of Bioactive Materials, Jeonbuk National University, Jeonju 54896, South Korea.
Biomater Res. 2025 Apr 10;29:0185. doi: 10.34133/bmr.0185. eCollection 2025.
This study devised a novel strategy to develop a functionally improved scaffold that enhances the healing of large bone defects via synergistic activation of vascularization and cell recruitment. To this end, we fabricated round and ring-shaped silk fibroin/ (SFBK) composite scaffolds. The round scaffolds had a diameter of 1.5 mm, and the ring-shaped scaffolds had a 6-mm diameter with a 1.5-mm hole in the center. All scaffolds had a 3-mm thickness. A portion of round SFBKs was cross-linked with stromal cell-derived factor 1 (SDF-1), and ring-shaped scaffolds underwent in vitro angiogenic stimulation, in vivo vascularization, or both. These scaffolds were assembled by fitting a round SFBK into the center of a vascularized SFBK scaffold before implantation into a rat model with critical-sized calvarial defects. Implantation with puzzle-fitted scaffolds promoted bone regeneration, and the scaffold that underwent both SDF-1 immobilization and vascularization processes showed the greatest efficacy in the healing of defects. The bone healing efficacy of puzzle-fitted scaffolds involved their ability to stimulate microvascular network formation, collagen synthesis, and stem cell recruitment at defects. -released calcium ions also participated in synergistic bone regeneration. These results suggest that the strategy of fitting SDF-1-linked SFBK into a vascularized ring-SFBK scaffold is useful in recruiting multipotent stem cells via newly formed blood vessels toward the center of scaffolds. This induces balanced and uniform bone regeneration. Overall, this study highlights the needs of calcium release, neovascularization, and stem cell recruitment for synergistic enhancement of bone regeneration.
本研究设计了一种新策略，以开发一种功能得到改善的支架，通过协同激活血管生成和细胞募集来促进大骨缺损的愈合。为此，我们制备了圆形和环形丝素蛋白/（SFBK）复合支架。圆形支架直径为1.5毫米，环形支架直径为6毫米，中心有一个1.5毫米的孔。所有支架厚度均为3毫米。一部分圆形SFBK与基质细胞衍生因子1（SDF-1）交联，环形支架进行体外血管生成刺激、体内血管化或两者皆有。这些支架通过将圆形SFBK安装到血管化SFBK支架的中心进行组装，然后植入具有临界尺寸颅骨缺损的大鼠模型中。植入拼接式支架促进了骨再生，同时经历SDF-1固定和血管化过程的支架在缺损愈合中显示出最大疗效。拼接式支架的骨愈合效果涉及其刺激缺损处微血管网络形成、胶原蛋白合成和干细胞募集的能力。释放的钙离子也参与了协同骨再生。这些结果表明，将与SDF-1连接的SFBK安装到血管化环形SFBK支架中的策略，有助于通过新形成的血管将多能干细胞募集到支架中心。这诱导了平衡且均匀的骨再生。总体而言，本研究强调了钙释放、新血管形成和干细胞募集对于协同增强骨再生的必要性。
