title: Pulp regeneration in a full-length human tooth root using a hierarchical nanofibrous microsphere system.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, USA; Department of Endodontics, School of Stomatology, Jilin University, Changchun 130021, PR China.
authors.forename: Xiangwei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, USA; Department of Stomatology, and Institute of Hard Tissue Development and Regeneration, The 2nd Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University, Changchun 130021, PR China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Biomedical Sciences, Texas A&M University Baylor College of Dentistry, Dallas, TX 75246, USA. Electronic address: xliu@bcd.tamhsc.edu.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003782:Dental Pulp / Q000187:drug effects / Q000502:physiology*; D005780:Gelatin / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D008863:Microspheres; D057139:Nanofibers / Q000737:chemistry*; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D034421:Sus scrofa; D014092:Tooth Root / Q000187:drug effects / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D005780:Gelatin; D006493:Heparin
keywords: Angiogenesis; Human dental pulp stem cell; Nanofibrous microspheres; Pulp regeneration; VEGF