Dual Delivery of Alendronate and E7-BMP-2 Peptide via Calcium Chelation to Mineralized Nanofiber Fragments for Alveolar Bone Regeneration

Sunil Kumar Boda, Hongjun Wang, Johnson V. John, Richard A. Reinhardt, Jingwei Xie

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The fixation and stability of dental implants is governed by the quality of the underlying alveolar bone. The current study investigates if the dual delivery of calcium chelating bone therapeutics from mineralized nanofiber fragments can help regenerate alveolar bone in vivo. Alendronate (ALN) or/and bone morphogenetic protein-2-mimicking peptide conjugated to a heptaglutamate moiety (E7-BMP-2) were incorporated onto mineralized nanofiber fragments of polylactide-co-glycolide-collagen-gelatin (PCG in 2:1:1 weight ratios) via calcium coupling/chelation. Two mg of the single-loaded (ALN) and coloaded (ALN + E7-BMP-2) mineralized nanofiber PCG grafts was filled into critical-sized (2 mm diameter × 2 mm depth) alveolar bone defects in rat maxillae and let heal for 4 weeks. X-ray microcomputed tomography analysis of the retrieved maxillae revealed significantly elevated new bone formation parameters for the ALN and ALN + E7-BMP-2 groups compared with the unfilled defect controls. However, no significant differences between the single and coloaded nanofiber grafts were noted. Furthermore, the histopathological analysis of the tissue sections divulged islands of new bone tissue in the ALN and ALN + E7-BMP-2 groups, whereas the control defect was covered with gingival tissue. Together, the presented strategy using mineralized nanofiber fragments in the sustained delivery of dual calcium chelating therapeutics could have potential applications in enhancing bone regeneration.

Original languageEnglish (US)
Pages (from-to)2368-2375
Number of pages8
JournalACS Biomaterials Science and Engineering
Volume6
Issue number4
DOIs
StatePublished - Apr 13 2020

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute of General Medical Science (NIGMS) at the NIH (2P20 GM103480) and National Institute of Dental and Craniofacial Research (NIDCR) at the NIH (1R21DE027516), NE LB606, and startup funds from the University of Nebraska Medical Center. XPS measurements were performed in the Nebraska Nanoscale Facility: National Nanotechnology Coordinated Infrastructure and the Nebraska Center for Materials and Nanoscience, which are supported by the National Science Foundation under award NNCI-1542182, and the Nebraska Research Initiative (NRI).

Publisher Copyright:
© 2020 American Chemical Society.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • alendronate
  • alveolar bone regeneration
  • calcium chelation
  • E7-BMP-2 peptides
  • mineralized nanofiber fragments

PubMed: MeSH publication types

  • Journal Article

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