Evaluation of BMP-2 and VEGF loaded 3D printed hydroxyapatite composite scaffolds with enhanced osteogenic capacity in vitro and in vivo
Evaluation of BMP-2 and VEGF loaded 3D printed hydroxyapatite composite scaffolds with enhanced osteogenic capacity in vitro and in vivo
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DOI：
10.1016/j.msec.2020.110893
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发表时间：
2020-07-01
影响因子：
7.9
通讯作者：
Ma, Jun
中科院分区：
文献类型：
--
作者：
Chen, Shangsi;Shi, Yufei;Ma, Jun
大面积骨缺损的修复是骨科手术中的一个挑战性课题。具有生长因子受控释放的多孔支架已经研究了多年。本研究通过低温3D打印和逐层（LBL）组装涂层制备了羟基磷灰石复合支架。将骨形态发生蛋白-2（BMP-2）和血管内皮生长因子（VEGF）负载到复合支架中。体外分析双生长因子的释放。通过在支架上培养MC 3 T3-E1细胞来评估细胞生长和成骨分化。在一个建立的兔模型的临界大小的颅骨缺损（直径15毫米），骨和血管生成性能后，植入支架进行了评价，通过显微计算机断层扫描（micro-CT）和染色切片。结果表明，该支架具有良好的多孔结构，并能持续释放两种生长因子。显微CT分析显示，BMP-2/VEGF复合支架材料能促进新骨形成。I型胶原和凝集素的免疫组化染色结果表明，BMP-2和VEGF诱导的成骨和血管生成能力更好。这些结果表明，新型复合支架结合BMP-2/VEGF具有成骨和血管生成能力，可以促进新骨的形成，并具有良好的质量。因此，负载BMP-2/VEGF的3D打印支架的组合可能为临床应用中的骨修复和再生提供潜在的解决方案。
Large-sized bone defect repair is a challenging task in orthopedic surgery. Porous scaffolds with controlled release of growth factors have been investigated for many years. In this study, a hydroxyapatite composite scaffold was prepared by 3D printing at low temperature and coating with layer-by-layer (LBL) assembly. Bone morphogenic protein-2 (BMP-2) and vascular endothelial growth factors (VEGF) were loaded into the composite scaffolds. The release of dual growth factors was analyzed in vitro. The cell growth and osteogenic differentiation were assessed by culturing MC3T3-E1 cells onto the scaffolds. In an established rabbit model of critical-sized calvarial defect (15 mm in diameter), the osteogenic and angiogenic properties after implantation of scaffolds were evaluated by micro-computed tomography (micro-CT) and stained sections. Our results showed that the scaffolds possessed well-designed porous structure and could release two growth factors in a sustained way. The micro-CT analysis showed that the scaffolds with BMP-2/VEGF could accelerate new bone formation. Findings of immunochemical staining of collagen type I and lectin indicated that better osteogenic and angiogenic properties induced by BMP-2 and VEGF. These results suggested that the novel composite scaffolds combined with BMP-2/VEGF had both osteogenic and angiogenic abilities which could enhance new bone formation with good quality. Thus, the combination of 3D printed scaffolds loaded with BMP-2/VEGF might provide a potential solution for bone repair and regeneration in clinical applications.