Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, 5020 Salzburg, Austria.
Department of Orthopedics and Traumatology, Salzburg University Hospital, Paracelsus Medical University, 5020 Salzburg, Austria.
Int J Mol Sci. 2021 Dec 28;23(1):283. doi: 10.3390/ijms23010283.
The repair of large bone defects remains challenging and often requires graft material due to limited availability of autologous bone. In clinical settings, collagen sponges loaded with excessive amounts of bone morphogenetic protein 2 (rhBMP-2) are occasionally used for the treatment of bone non-unions, increasing the risk of adverse events. Therefore, strategies to reduce rhBMP-2 dosage are desirable. Silk scaffolds show great promise due to their favorable biocompatibility and their utility for various biofabrication methods. For this study, we generated silk scaffolds with axially aligned pores, which were subsequently treated with 10× simulated body fluid (SBF) to generate an apatitic calcium phosphate coating. Using a rat femoral critical sized defect model (CSD) we evaluated if the resulting scaffold allows the reduction of BMP-2 dosage to promote efficient bone repair by providing appropriate guidance cues. Highly porous, anisotropic silk scaffolds were produced, demonstrating good cytocompatibility in vitro and treatment with 10× SBF resulted in efficient surface coating. In vivo, the coated silk scaffolds loaded with a low dose of rhBMP-2 demonstrated significantly improved bone regeneration when compared to the unmineralized scaffold. Overall, our findings show that this simple and cost-efficient technique yields scaffolds that enhance rhBMP-2 mediated bone healing.
大骨缺损的修复仍然具有挑战性,由于自体骨的可用性有限,通常需要移植物材料。在临床环境中,偶尔会使用负载过量骨形态发生蛋白 2(rhBMP-2)的胶原海绵来治疗骨不连,从而增加不良事件的风险。因此,减少 rhBMP-2 剂量的策略是可取的。丝素支架由于其良好的生物相容性和各种生物制造方法的实用性,显示出巨大的应用前景。在这项研究中,我们生成了具有轴向排列孔的丝素支架,随后用 10×模拟体液(SBF)处理以生成磷灰石钙涂层。使用大鼠股骨临界尺寸缺损模型(CSD),我们评估了所得支架是否通过提供适当的引导线索来减少 BMP-2 剂量以促进有效的骨修复。生成了具有高多孔性和各向异性的丝素支架,体外表现出良好的细胞相容性,用 10×SBF 处理后,表面涂层效果显著。在体内,与未矿化支架相比,负载低剂量 rhBMP-2 的涂层丝素支架显著改善了骨再生。总的来说,我们的研究结果表明,这种简单且具有成本效益的技术可以产生增强 rhBMP-2 介导的骨愈合的支架。