title: Characterization of a Vascular Endothelial Growth Factor-loaded Bioresorbable Delivery System for Pulp Regeneration.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is a signal protein that stimulates angiogenesis and vasculogenesis and has been used in tissue regeneration and pulp regeneration experimental models. The purpose of this study was to develop a delivery system composed of a biodegradable fiber and controlled release of VEGF to promote cell viability and secure an adequate blood supply for the survival of human stem cells of the apical papilla (SCAP) favoring endodontic regenerative procedures.
  
  
  METHODS
  We developed a polydioxanone fiber, 50 μm in diameter, loaded with VEGF at a linear concentration of 12.2 ng/cm. Cytotoxic effects of the VEGF-loaded fiber (VF) on SCAP and mouse fibroblasts were assessed by using a multiparametric assay kit (XTT-NR-CVDE [Xenometrix, Allschwil, Switzerland]). We evaluated VF-induced mRNA expression of downstream growth factors by using a human growth factor Taqman array in real-time polymerase chain reaction. We also assessed the in vivo subcutaneous reaction of C57BL/6 mice to implants of VF alone and human root fragments (10 mm in length) filled with VF after 10, 20, and 45 days. Statistical analyses were performed by using analysis of variance and Student t tests or non-parametric alternatives.
  
  
  RESULTS
  Enzyme-linked immunosorbent assay verified detectable concentrations of released VEGF in solution for 25 days. No cytotoxicity was observed on SCAP and mouse fibroblasts treated with VEGF. In addition, VEGF treatment also induced the expression of additional growth factors with roles in tissue and blood vessel formation and neuroprotective function. Implantation of VF and root fragments filled with VF showed biocompatibility in vivo, promoting new blood vessels and connective tissue formation into the root canal space with negligible inflammation.
  
  
  CONCLUSIONS
  Our results show that the VF used in this study is biocompatible and may be a promising scaffold for additional optimization and use in endodontic regenerative procedures.
authors.affiliation: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Mamatha
authors.initials: M
authors.lastname: Yadlapati
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo (FOB/USP), Bauru, São Paulo, Brazil; Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Claudia
authors.initials: C
authors.lastname: Biguetti
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo (FOB/USP), Bauru, São Paulo, Brazil; Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas; Department of Conservative Dentistry, University of Chile School of Dentistry, Santiago, Chile.
authors.forename: Franco
authors.initials: F
authors.lastname: Cavalla
authors.affiliation: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Francisco
authors.initials: F
authors.lastname: Nieves
authors.affiliation: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bessey
authors.affiliation: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Pedram
authors.initials: P
authors.lastname: Bohluli
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of São Paulo (FOB/USP), Bauru, São Paulo, Brazil.
authors.forename: Gustavo Pompermaier
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas; Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.affiliation: Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas; Department of Diagnostic and Biomedical Sciences, University of Texas School of Dentistry at Houston, Houston, Texas.
authors.forename: Walid D
authors.initials: WD
authors.lastname: Fakhouri
authors.affiliation: Department of Endodontics, University of Texas School of Dentistry at Houston, Houston, Texas; Center for Craniofacial Research, University of Texas School of Dentistry at Houston, Houston, Texas. Electronic address: Renato.M.Silva@uth.tmc.edu.
authors.forename: Renato Menezes
authors.initials: RM
authors.lastname: Silva
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D003771:Dental Papilla / Q000187:drug effects / Q000502:physiology; D003782:Dental Pulp / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016687:Polydioxanone; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D014092:Tooth Root / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001672:Biocompatible Materials; D042461:Vascular Endothelial Growth Factor A; D016687:Polydioxanone
keywords: Biomaterials; VEGF; growth factors; pulp regeneration