Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system.
UNLABELLED
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 SIGNIFICANCE
The 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.
['Li|Xiangwei|X|', 'Ma|Chi|C|', 'Xie|Xiaohua|X|', 'Sun|Hongchen|H|', 'Liu|Xiaohua|X|']
D000818:Animals D002417:Cattle D002448:Cell Adhesion D049109:Cell Proliferation D003782:Dental Pulp D005780:Gelatin D006493:Heparin D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D007150:Immunohistochemistry D008863:Microspheres D057139:Nanofibers D012038:Regeneration D013234:Stem Cells D034421:Sus scrofa D014092:Tooth Root D042461:Vascular Endothelial Growth Factor A
Pulp regeneration Nanofibrous microspheres VEGF Angiogenesis Human dental pulp stem cell