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首页> 外文期刊>Cell and Tissue Research >Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair
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Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair

机译：编码BMP2的腺相关病毒的合成支架涂层可促进内源性骨修复

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Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.
机译：功能化的生物材料支架通过引入成骨线索来刺激内源性修复机制，为治疗大骨缺损提供了一种替代骨移植的潜在选择。我们首先量化了编码骨形态发生蛋白2（scAAV2.5-BMP2）的自我互补腺相关病毒载体增强人干细胞成骨分化能力。在二维培养中，与对照相比，scAAV2.5-BMP2转导的人间充质干细胞（hMSC）显示出BMP2产量和碱性磷酸酶活性显着增加。接种于scAA​​V2.5-BMP2涂层的三维多孔聚合物聚（ε-己内酯）（PCL）支架上的hMSCs和人羊水衍生干细胞（hAFS细胞）在12个月中与对照组相比也显示BMP2产量显着增加尽管仅用hMSC接种的支架显示出显着增加的矿物质形成，但培养了数周的时间。将涂有scAAV2.5-BMP2的PCL支架植入具有临界大小的免疫受损的大鼠股骨缺损中，无论是否预接种hMSC，分别代表离体和体内基因治疗。 12周后，与对照相比，用脱细胞的scAAV2.5-BMP2涂层支架处理的缺损显示出骨桥增加，并且骨向内生长和力学性能显着提高，而用hMSCs预先植入的scAAV2.5-BMP2支架处理的缺损未能与控件相比显示出显着差异。汇总后，用scAAV2.5-BMP2涂层的支架进行缺陷处理（无论是否包含预接种的hMSC），与对照组相比，导致在所有时间点缺陷矿物质的形成显着增加，并且机械性能提高。因此，这项研究为原位组织工程化的骨再生提供了一种新型的无脱细胞无骨移植内源性修复疗法。

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