Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system
Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system
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DOI：
10.1016/j.actbio.2016.02.040
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发表时间：
2016-04-15
影响因子：
9.7
通讯作者：
Liu, Xiaohua
中科院分区：
文献类型：
--
作者：
Li, Xiangwei;Ma, Chi;Liu, Xiaohua
虽然使用组织工程策略进行牙髓再生的研究已经有十多年了，但在真正模拟临床牙髓治疗的全长人牙根中使用一端密封成功地再生牙髓组织尚未实现。为了解决这一挑战，我们设计并合成了一种独特的分层生长因子负载纳米纤维微球支架系统。在该系统中，血管内皮生长因子（VEGF）与肝素结合，并被包裹在肝素共轭明胶纳米球中，并进一步固定在可注射的聚l -乳酸（PLLA）微球的纳米纤维中。这种分级微球系统不仅可以防止VEGF变性和降解，而且还可以很好地控制其持续释放。此外，纳米纤维PLLA微球将细胞外基质模拟结构与高度多孔的可注射形式相结合，有效地容纳牙髓干细胞（DPSCs）并支持其增殖和牙髓组织形成。我们的体内研究表明，牙髓样组织的再生成功，覆盖了整个根管的根尖和中三分之一，并达到了冠状三分之一。此外，大量血管在整个管道中再生。我们的工作首次证明了在全长根管中髓质组织再生的成功，使其成为再生牙髓学的重要一步。全牙根管中牙髓组织的再生一直是再生牙髓学领域的最大挑战之一，也是其临床应用的最大障碍之一。在这项研究中，我们开发了一种独特的方法来解决这一挑战，并首次成功地在全长根管中再生活髓组织，使其成为再生牙髓学的重要一步。本研究将对牙科生物材料和颅面组织工程界产生积极的科学影响和兴趣。(C) 2016材料学报Elsevier Ltd.出版。版权所有。
While pulp regeneration using tissue engineering strategy has been explored for over a decade, successful regeneration of pulp tissues in a full-length human root with a one-end seal that truly simulates clinical endodontic treatment has not been achieved. To address this challenge, we designed and synthesized a unique hierarchical growth factor-loaded nanofibrous microsphere scaffolding system. In this system, vascular endothelial growth factor (VEGF) binds with heparin and is encapsulated in heparin conjugated gelatin nanospheres, which are further immobilized in the nanofibers of an injectable poly (L-lactic acid) (PLLA) microsphere. This hierarchical microsphere system not only protects the VEGF from denaturation and degradation, but also provides excellent control of its sustained release. In addition, the nanofibrous PLLA microsphere integrates the extracellular matrix-mimicking architecture with a highly porous injectable form, efficiently accommodating dental pulp stem cells (DPSCs) and supporting their proliferation and pulp tissue formation. Our in vivo study showed the successful regeneration of pulp like tissues that fulfilled the entire apical and middle thirds and reached the coronal third of the full-length root canal. In addition, a large number of blood vessels were regenerated throughout the canal. For the first time, our work demonstrates the success of pulp tissue regeneration in a full-length root canal, making it a significant step toward regenerative endodontics.Statement of SignificanceThe regeneration of pulp tissues in a full-length tooth root canal has been one of the greatest challenges in the field of regenerative endodontics, and one of the biggest barriers for its clinical application. In this study, we developed a unique approach to tackle this challenge, and for the first time, we successfully regenerated living pulp tissues in a full-length root canal, making it a significant step toward regenerative endodontics.This study will make positive scientific impact and interest the broad and multidisciplinary readership in the dental biomaterials and craniofacial tissue engineering community. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.