Synergistic effect of stem cells from human exfoliated deciduous teeth and rhBMP-2 delivered by injectable nanofibrous microspheres with different surface modifications on vascularized bone regeneration
Synergistic effect of stem cells from human exfoliated deciduous teeth and rhBMP-2 delivered by injectable nanofibrous microspheres with different surface modifications on vascularized bone regeneration
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人脱落乳牙干细胞与不同表面修饰的可注射纳米纤维微球递送的 rhBMP-2 对血管化骨再生的协同作用
DOI：
10.1016/j.cej.2019.03.151
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发表时间：
2019-08-15
影响因子：
15.1
通讯作者：
Cai, Qing
中科院分区：
文献类型：
--
作者：
Fang, Tengjiaozi;Yuan, Zuoying;Cai, Qing
为了为骨再生提供合适的三维微环境，我们选择了具有不同表面修饰的可注射聚乳酸纳米纤维微球（PLLA NF-Ms）作为细胞微载体或蛋白质载体。结果表明，聚多巴胺（PDA）修饰的NF-Ms （PDA-NF-Ms）对人脱落乳牙（SHED）干细胞具有良好的亲和力，与NF-Ms结合的肝素-多巴胺（Hep-Dopa NF-Ms）能够有效地固定化并缓慢释放重组人骨形态发生蛋白2 （rhBMP-2）。采用异位皮下植入和正位颅骨缺损裸鼠模型（φ = 4 mm）进行体内评价。结果表明，PDA-NF-Ms可支持4周以上的棚舍生存。所有转染SHED/PDA-NF-Ms的实验组均显示血管生成活性。但是，在异位植入中，没有发现SHED/PDA-NF-Ms对成骨的影响，这与颅缺损的结果不同。Hep-Dopa NF-Ms释放的rhBMP-2对异位和正位骨组织再生均有显著的引导作用。在8周时，BMP-2组和双组均显示大量原位骨形成，尽管micro-CT定量结果显示两者之间没有显著差异。SHED组和Dual组血管增多，证实再生骨组织质量提高。因此，在同时植入SHED/PDA-NF-Ms和rhbmp -2负载的Hep-Dopa NF-Ms后，人们对血管化骨组织的再生寄予了很高的期望。本研究中开发的策略代表了一种有希望的方法，令人满意地促进骨再生。
To provide a suitable 3D microenvironment for bone regeneration, we selected the injectable poly (l-lactic acid) nanofibrous microspheres (PLLA NF-Ms) with different surface modifications to serve as cell micro-carriers or protein vehicles on-demand. Results showed that polydopamine (PDA) modified NF-Ms (PDA-NF-Ms) exhibited good affinity for stem cells from human exfoliated deciduous teeth (SHED), and Heparin-Dopamine (Hep-Dopa) conjugated with NF-Ms (Hep-Dopa NF-Ms) are able to immobilize and slowly release recombinant human bone morphogenic protein-2 (rhBMP-2) efficiently. In vivo evaluations were carried out in both ectopic subcutaneous implantation and orthotopic cranial bone defect nude mouse models (phi = 4 mm). The results suggested that PDA-NF-Ms could support SHED survival over 4 weeks. All experimental groups with SHED/PDA-NF-Ms engraftment showed angiogenesis activity. But, no effect of SHED/PDA-NF-Ms on osteogenesis was found in ectopic implantation, which is different from the result in cranial defect. The rhBMP-2 released from Hep-Dopa NF-Ms could significantly guide bone tissue regeneration in both ectopic and orthotopic site. At 8 weeks, both BMP-2 group and dual group showed large amounts of bone formation in situ, despite the fact that quantitative results of micro-CT did not demonstrate significant difference between them. More blood vessels were observed in SHED and Dual groups, which verifies the quality improvement of regenerated osseous tissues. Regeneration of vascularized bone tissue was, thus, highly expected upon implanting SHED/PDA-NF-Ms and rhBMP-2-loaded Hep-Dopa NF-Ms together. The strategy developed in this study represents a promising method for satisfactorily promoting bone regeneration.