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首页> 外文期刊>Biomaterials Science >3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and osteogenesis
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3D-printed dimethyloxallyl glycine delivery scaffolds to improve angiogenesis and osteogenesis

机译：3D打印的二甲基草烯丙基甘氨酸递送支架可改善血管生成和成骨作用

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Angiogenesis-osteogenesis coupling processes are vital in bone tissue engineering. Normal biomaterials implanted in bone defects have issues in the sufficient formation of blood vessels, especially in the central part. Single delivery of vascular endothelial growth factors (VEGF) to foci in previous studies did not show satisfactory results due to low loading doses, a short protein half-life and low efficiency. Development of a hypoxia-mimicking microenvironment for cells by local prolyl-4-hydroxylase inhibitor release, which can stabilize hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression, is an alternative method. The aim of this study was to design a dimethyloxallyl glycine (DMOG) delivering scaffold composed of mesoporous bioactive glasses and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) polymers (MPHS scaffolds), so as to investigate whether the sustained release of DMOG promotes local angiogenesis and bone healing. The morphology and microstructure of composite scaffolds were characterized. The DMOG release patterns from scaffolds loaded with different DMOG dosages were evaluated, and the effects of DMOG delivery on human bone marrow stromal cell (hBMSC) adhesion, viability, proliferation, osteogenic differentiation and angiogenic-relative gene expressions with scaffolds were also investigated. In vivo studies were carried out to observe vascular formations and new bone ingrowth with DMOG-loaded scaffolds. The results showed that DMOG could be released in a sustained manner over 4 weeks from MPHS scaffolds and obviously enhance the angiogenesis and osteogenesis in the defects. Microfil perfusion showed a significantly increased formation of vessels in the defects with DMOG delivery. Furthermore, micro-CT imaging and fluorescence labeling indicated larger areas of bone formation for DMOG-loaded scaffolds. It is concluded that MPHS-DMOG scaffolds are promising for enhancing bone healing of osseous defects.
机译：血管生成-成骨耦合过程在骨组织工程中至关重要。植入骨缺损中的正常生物材料存在血管充分形成的问题，尤其是在中部。由于负载量低，蛋白半衰期短和效率低，在以前的研究中将血管内皮生长因子（VEGF）单次递送至病灶未显示出令人满意的结果。通过局部脯氨酰-4-羟化酶抑制剂释放来发展细胞模拟缺氧的微环境，可以稳定缺氧诱导因子1α（HIF-1 alpha）的表达，这是另一种方法。这项研究的目的是设计一种由中孔生物活性玻璃和聚（3-羟基丁酸酯-co-3-羟基己酸酯）聚合物（MPHS支架）组成的二甲基乙二烯丙基甘氨酸（DMOG）输送支架，以研究是否可持续释放DMOG促进局部血管生成和骨骼愈合。表征了复合支架的形态和微观结构。评估了载有不同DMOG剂量的支架的DMOG释放模式，并研究了DMOG递送对支架对人骨髓基质细胞（hBMSC）粘附，生存力，增殖，成骨分化和血管生成相关基因表达的影响。进行了体内研究，以观察使用DMOG负载的支架的血管形成和新骨向内生长。结果表明，DMOG可以在MPHS支架上持续释放4周以上，并明显增强缺损的血管生成和成骨作用。 Microfil灌注显示在DMOG输送中缺陷处血管的形成显着增加。此外，micro-CT成像和荧光标记显示了装载DMOG的支架更大的骨形成区域。结论是，MPHS-DMOG支架有望增强骨缺损的骨愈合。

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