Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 6, Issue 4, Pages 2368-2375Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.0c00145
Keywords
alendronate; E7-BMP-2 peptides; calcium chelation; mineralized nanofiber fragments; alveolar bone regeneration
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Funding
- National Institute of General Medical Science (NIGMS) at the NIH [2P20 GM103480]
- National Institute of Dental and Craniofacial Research (NIDCR) at the NIH [1R21DE027516, NE LB606]
- University of Nebraska Medical Center
- National Science Foundation [NNCI-1542182]
- Nebraska Research Initiative (NRI)
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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 x 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.
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