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Dual Delivery of Alendronate and E7-BMP-2 Peptide via Calcium Chelation to Mineralized Nanofiber Fragments for Alveolar Bone Regeneration
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-03-13 , DOI: 10.1021/acsbiomaterials.0c00145
Sunil Kumar Boda 1, 2 , Hongjun Wang 1 , Johnson V. John 1 , Richard A. Reinhardt 3 , Jingwei Xie 1
Affiliation  

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.

中文翻译:

通过钙螯合双重递送阿仑膦酸盐和E7-BMP-2肽到矿化的纳米纤维碎片,用于肺泡骨再生。

牙种植体的固定和稳定性取决于底层牙槽骨的质量。目前的研究调查了矿物质化的纳米纤维碎片中钙螯合骨治疗剂的双重递送是否可以帮助体内再生牙槽骨。阿仑膦酸盐(ALN)或/和缀合至heptaglutamate部分骨形态发生蛋白2 -模拟肽(E7-BMP-2)掺入到聚交酯的矿化纳米纤维片段-乙交酯-胶原蛋白-明胶(PCG重量比为2:1:1)通过钙偶联/螯合作用。将两毫克单负荷(ALN)和共负荷(ALN + E7-BMP-2)矿化的纳米纤维PCG移植物填充到大鼠上颌骨的临界尺寸(直径2 mm×深度2 mm)的牙槽骨缺损中,并进行愈合。 4个星期 X射线微计算机断层摄影术分析所取回的上颌骨,与未填充的缺损对照组相比,显着提高了ALN和ALN + E7-BMP-2组的新骨形成参数。但是,在单纳米纤维移植物和共加载纳米纤维移植物之间未发现明显差异。此外,组织切片的组织病理学分析揭示了ALN和ALN + E7-BMP-2组中新骨组织的岛状,而对照缺损被牙龈组织覆盖。一起,
更新日期:2020-04-23
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