Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp.

Nanofibrous spongy microspheres for the delivery of hypoxia-primed human dental pulp stem cells to regenerate vascularized dental pulp.
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DOI:
10.1016/j.actbio.2016.01.032
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发表时间:
2016-03
期刊:
影响因子:
9.7
通讯作者:
Ma PX
Ma PX
中科院分区:
工程技术1区
文献类型:
--
作者:
Kuang R;Zhang Z;Jin X;Hu J;Shi S;Ni L;Ma PX

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牙髓感染和坏死是广泛存在的疾病。传统的牙髓治疗会导致牙齿失活和变弱。在这项工作中,我们合成了一种新的星形聚合物,可以自组装成独特的纳米纤维海绵微球(NF-SMS),用于将人牙髓干细胞(hDPSCs)携带到牙髓腔中以再生活牙髓组织。结果发现,与对照细胞载体相比,NF-SMS显著增强了hDPSCs的附着、增殖、成牙分化和血管生成。此外,在3D缺氧培养中,NF-SMS促进了hdpsc血管内皮生长因子(VEGF)的表达。将缺氧诱导的hdpsc /NF-SMS复合物注射到清洁的兔磨牙牙髓腔中,用于小鼠皮下植入。4周后,与对照组(hDPSCs单独培养组、NF-SMS单独培养组和hDPSCs/NF-SMS预培养组)相比,缺氧组显著增强牙髓腔内血管生成,促进牙本质-牙髓界面上成牙釉质样细胞的形成。此外,在大鼠原位牙髓修复模型中,注射缺氧诱导的hdpsc /NF-SMS,使其充分填充牙髓腔,再生出血管丰富、组织结构与天然牙髓相似的牙髓样组织。
Dental pulp infection and necrosis are widespread diseases. Conventional endodontic treatments result in a devitalized and weakened tooth. In this work, we synthesized novel star-shaped polymer to self-assemble into unique nanofibrous spongy microspheres (NF-SMS), which were used to carry human dental pulp stem cells (hDPSCs) into the pulp cavity to regenerate living dental pulp tissues. It was found that NF-SMS significantly enhanced hDPSCs attachment, proliferation, odontogenic differentiation and angiogenesis, as compared to control cell carriers. Additionally, NF-SMS promoted vascular endothelial growth factor (VEGF) expression of hDPSCs in a 3D hypoxic culture. Hypoxia-primed hDPSCs/NF-SMS complexes were injected into the cleaned pulp cavities of rabbit molars for subcutaneous implantation in mice. After 4 weeks, the hypoxia group significantly enhanced angiogenesis inside the pulp chamber and promoted the formation of ondontoblast-like cells lining along the dentin-pulp interface, as compared to the control groups (hDPSCs alone group, NF-SMS alone group, and hDPSCs/NF-SMS group pre-cultured under normoxic conditions). Furthermore, in an in situ dental pulp repair model in rats, hypoxia-primed hDPSCs/NF-SMS were injected to fully fill the pulp cavity and regenerate pulp-like tissues with a rich vasculature and a histological structure similar to the native pulp.
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