Dual Delivery of Alendronate and E7-BMP‑2 Peptide\nvia Calcium Chelation to Mineralized Nanofiber Fragments for Alveolar\nBone Regeneration

Abstract

The fixation and\nstability of dental implants is governed by the\nquality of the underlying alveolar bone. The current study investigates\nif the dual delivery of calcium chelating bone therapeutics from mineralized\nnanofiber fragments can help regenerate alveolar bone <i>in vivo</i>. Alendronate (ALN) or/and bone morphogenetic protein-2-mimicking\npeptide conjugated to a heptaglutamate moiety (E7-BMP-2) were incorporated\nonto mineralized nanofiber fragments of polylactide-<i>co</i>-glycolide–collagen–gelatin (PCG in 2:1:1 weight ratios)\nvia calcium coupling/chelation. Two mg of the single-loaded (ALN)\nand coloaded (ALN + E7-BMP-2) mineralized nanofiber PCG grafts was\nfilled into critical-sized (2 mm diameter × 2 mm depth) alveolar\nbone defects in rat maxillae and let heal for 4 weeks. X-ray microcomputed\ntomography analysis of the retrieved maxillae revealed significantly\nelevated new bone formation parameters for the ALN and ALN + E7-BMP-2\ngroups compared with the unfilled defect controls. However, no significant\ndifferences between the single and coloaded nanofiber grafts were\nnoted. Furthermore, the histopathological analysis of the tissue sections\ndivulged islands of new bone tissue in the ALN and ALN + E7-BMP-2\ngroups, whereas the control defect was covered with gingival tissue.\nTogether, the presented strategy using mineralized nanofiber fragments\nin the sustained delivery of dual calcium chelating therapeutics could\nhave potential applications in enhancing bone regeneration.