Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells.

Nanofibrous spongy microspheres enhance odontogenic differentiation of human dental pulp stem cells.
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DOI:
10.1002/adhm.201500308
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发表时间:
2015-09-16
影响因子:
10
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;Gupte MJ;Ni L;Ma PX

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虽然龋齿困扰着近100%的成年人和60-70%的儿童,但由于其复杂的解剖结构和成牙本质细胞的缺乏,牙本质再生具有挑战性。在这项研究中,一种新的可注射的细胞载体,纳米纤维海绵微球(NF-SMS),开发的牙本质再生。采用自组装和热致相分离技术合成了生物可降解、生物相容的聚L-乳酸-聚L-赖氨酸嵌段共聚物,并将其组装成纳米纤维素微球。我们假设,与没有孔结构的纳米纤维微球(NF-MS)和既没有纳米纤维也没有孔结构的传统固体微球(S-MS)相比,在整个纳米纤维微球中具有互连孔的NF-SMS可以增强人牙髓干细胞(hDPSC)的增殖和牙向分化。在培养的前9天期间,hDPSC在NF-SMS上比在NF-MS和S-MS上增殖显著更快(p < 0.05)。体外成牙诱导后,NF-SMS组的ALP含量、OCN、BSP、COL 1、DSPP基因表达水平、钙含量和DSPP蛋白含量均显著高于NF-MS和S-MS对照组。此外,6周后皮下注射的hDPSCs和微球到裸鼠,组织学分析表明,NF-SMS支持上级的牙本质样组织形成相比,NF-MS和S-MS。总之,结果支持我们的假设,并表明,新的NF-SMS作为一种可注射的细胞载体,牙本质再生的巨大潜力。纳米纤维海绵状微球(NF-SMS)被开发用于牙本质再生。与不含微孔的纳米纤维微球(NF-MS)和既不含纳米纤维也不含孔的常规固体微球(S-MS)相比,NF-SMS增强人牙髓干细胞的增殖和牙向分化。NF-SMS还可促进体内牙本质基质沉积,显示出作为牙本质再生的可注射细胞载体的巨大潜力。
While dental caries afflicts nearly 100% adults and 60–70% children, dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF-SMS), was developed for dentin regeneration. Biodegradable and biocompatible poly(L-lactic acid)-block-poly(L-lysine) copolymers were synthesized and fabricated into NF-SMS using self-assembly and thermally-induced phase separation techniques. We hypothesized that NF-SMS with interconnected pores throughout the nanofibrous microspheres could enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF-MS) without pore structure and conventional solid microspheres (S-MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferated significantly faster on NF-SMS than on NF-MS and S-MS (p < 0.05). Following in vitro odontogenic induction, all the examined odontogenic markers including ALP content, OCN, BSP, COL1, DSPP gene expression levels, calcium content and DSPP protein content were found significantly higher in the NF-SMS group than in the NF-MS and S-MS control groups. Furthermore, 6 wk after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis showed that NF-SMS supported superior dentin-like tissue formation compared to NF-MS and S-MS. Taken together, the results supported our hypothesis and suggest that the novel NF-SMS have great potential as an injectable cell carrier for dentin regeneration. Nanofibrous spongy microspheres (NF-SMS) are developed for dentin regeneration. NF-SMS enhance the proliferation and odontogenic differentiation of human dental pulp stem cells, compared to nanofibrous microspheres (NF-MS) without micro-pores and conventional solid microspheres (S-MS) with neither nanofibers nor pores. NF-SMS also enhance dentin matrix deposition in vivo, demonstrating great potential as an injectable cell carrier for dentin regeneration.