Boda Sunil Kumar, Wang Hongjun, John Johnson V, Reinhardt Richard A, Xie Jingwei
Department of Surgery-Transplant and Mary & Dick Holland Regenerative Medicine Program, College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
Minnesota Dental Research Center for Biomaterials and Biomechanics (MDRCBB), Department of Restorative Sciences, School of Dentistry, University of Minnesota, Minneapolis, Minnesota 55455, United States.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2368-2375. doi: 10.1021/acsbiomaterials.0c00145. Epub 2020 Mar 20.
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 . 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--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.
牙种植体的固定和稳定性取决于其下方牙槽骨的质量。本研究调查了从矿化纳米纤维片段中双重递送钙螯合骨治疗剂是否有助于牙槽骨再生。通过钙偶联/螯合，将阿仑膦酸盐（ALN）或/和与七谷氨酸部分偶联的骨形态发生蛋白-2模拟肽（E7-BMP-2）掺入聚丙交酯-乙交酯-胶原蛋白-明胶（重量比为2:1:1的PCG）的矿化纳米纤维片段中。将2mg单负载（ALN）和共负载（ALN + E7-BMP-2）的矿化纳米纤维PCG移植物填充到大鼠上颌骨的临界尺寸（直径2mm×深度2mm）牙槽骨缺损中，并让其愈合4周。对取出的上颌骨进行X射线微计算机断层扫描分析显示，与未填充缺损的对照组相比，ALN组和ALN + E7-BMP-2组的新骨形成参数显著升高。然而，单负载和共负载纳米纤维移植物之间未观察到显著差异。此外，组织切片的组织病理学分析显示，ALN组和ALN + E7-BMP-2组中有新骨组织岛，而对照缺损处覆盖着牙龈组织。总之，所提出的使用矿化纳米纤维片段持续递送双重钙螯合治疗剂的策略在促进骨再生方面可能具有潜在应用。
