PLGA/β-TCP composite scaffold incorporating salvianolic acid B promotes bone fusion by angiogenesis and osteogenesis in a rat spinal fusion model. (March 2019)

• Record Type: Journal Article
• Authors: Lin, Sien; Cui, Liao; Chen, Guanghua; Huang, Jianping; Yang, Yanhua; Zou, Kaijie; Lai, Yuxiao; Wang, Xinluan; Zou, Liyi; Wu, Tie; Cheng, Jack Chun Yiu; Li, Gang; Wei, Bo; Lee, Wayne Yuk Wai
• Is Part Of: Biomaterials. Volume 196(2019)
• Page Start: 109
• Page End: 121
• Publication Date: 2019-03
• Subjects: Spinal fusion -- Tissue engineering -- Salvianolic acid B -- Osteogenesis -- Angiogenesis -- Bone graft; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2018.04.004
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Spinal disorders often require surgical treatment called spinal fusion to restore a stabilized spine where bone grafts are implanted for the fusion of adjacent vertebras. In this study, we developed a bioactive composite scaffold incorporated with salvianolic acid B (SB), an active component extracted from Danshen. This study aimed to evaluate the effects of SB-incorporated porous scaffold on spinal fusion models. The composite scaffolds composed of poly (lactic-co-glycolic acid) and tricalcium phosphate (PLGA/β-TCP) were fabricated with low-temperature rapid prototyping technique, which incorporated SB at low (SB-L), middle (SB-M), high (SB-H) doses, and pure PLGA/β-TCP as blank control (Con). The release profile of SB from the scaffolds was determined by high performance liquid chromatography. Osteoconductive and osteoinductive properties of the scaffolds were reflected by the osteogenic differentiation ability of rat primary mesenchymal stem cells. The angiogenesis was determined by the forming of tube-like structures resembling capillaries using endothelial cell line (EA hy9.26). A well-established spinal fusion model was used to evaluate the in vivo bony fusion. Animals were transplanted with scaffolds, or autografts from iliac crest as positive controls. Micro-computed tomography (CT) analysis, CT-based angiography, manual palpation test, histomorphometry, and histology were performed after 8 weeks of transplantation. Results revealed that incorporated SB was steadily released from the scaffolds. The aliquot of released SB promoted osteogenesis and angiogenesis in vitro in a dose-dependent manner. In animal study, a dose-dependent effect of SB on new bone formation, mineral apposition rate, and vessel density within the scaffold were demonstrated. Manual palpation test showed little numerical improvement in fusion rate when compared with the blank controls. In summary, our results suggested that SB-incorporated PLGA/β-TCP composite scaffold could enhance bony fusion through the promotion of osteogenesis and angiogenesis. Graphical abstract: Salvianolic acid B (SB) has been proved to be a bioactive phytomolecue with osteoinductive and angiogenic effect. We designed a porous scaffold based on PLGA/β-TCP incorporated with SB by low-temperature 3D printing technology. Our results also suggested that SB incorporation could enhance bony fusion of PLGA/β-TCP composite scaffold through the promoting effect of SB on osteogenesis and angiogenesis.Image 1