State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Palo Alto, CA, USA.
Dent Mater. 2020 Oct;36(10):1303-1313. doi: 10.1016/j.dental.2020.06.003. Epub 2020 Jul 7.
Compared to autologous bone grafts, allogeneic bone grafts integrate slowly, which can adversely affect clinical outcomes. Here, our goal was to understand the molecular mechanisms underlying graft incorporation, and then test clinically feasible methods to accelerate this process.
Wild-type and transgenic Wnt "reporter" mice were used in a vertical ridge augmentation procedure. The surgery consisted of tunneling procedure to elevate the maxillary edentulous ridge periosteum, followed by the insertion of bone graft. Micro-computed tomographic imaging, and molecular/cellular analyses were used to follow the bone graft over time. Sclerostin null mice, and mice carrying an activated form of β-catenin were evaluated to understand how elevated Wnt signaling impacted edentulous ridge height and based on these data, a biomimetic strategy was employed to combine bone graft particles with a formulation of recombinant WNT protein. Thereafter, the rate of graft incorporation was evaluated.
Tunneling activated osteoprogenitor cell proliferation from the periosteum. If graft particles were present, then osteoprogenitor cells attached to the matrix and gave rise to new bone that augmented edentulous ridge height. Graft particles alone did not stimulate osteoprogenitor cell proliferation. Based on the thicker edentulous ridges in mice with amplified Wnt signaling, a strategy was undertaken to load bone graft particles with WNT; this combination was sufficient to accelerate the initial step of graft incorporation.
Local delivery of a WNT protein therapeutic has the potential to accelerate graft incorporation, and thus shorten the time to when the graft can support a dental implant.
与自体骨移植物相比，同种异体骨移植物的整合速度较慢，这可能会对临床结果产生不利影响。在这里，我们的目标是了解移植物整合的分子机制，然后测试临床上可行的方法来加速这一过程。
使用野生型和转基因 Wnt“报告”小鼠进行垂直牙槽嵴增高术。手术包括隧道手术以提升上颌无牙牙槽嵴骨膜，然后插入骨移植物。使用微计算机断层扫描成像和分子/细胞分析来随时间跟踪骨移植物。评估 Sclerostin 缺失小鼠和携带激活型β-catenin 的小鼠，以了解升高的 Wnt 信号如何影响无牙牙槽嵴高度，并根据这些数据，采用仿生策略将骨移植物颗粒与重组 WNT 蛋白制剂结合。然后，评估移植物整合的速度。
隧道激活了骨祖细胞从骨膜中的增殖。如果存在移植物颗粒，那么骨祖细胞就会附着在基质上，并产生新的骨，从而增加无牙牙槽嵴的高度。单独的移植物颗粒不会刺激骨祖细胞的增殖。基于 Wnt 信号放大的小鼠中牙槽嵴更厚，我们采取了一种策略，即将 WNT 加载到骨移植物颗粒上；这种组合足以加速移植物整合的初始步骤。
局部递送 WNT 蛋白治疗剂有可能加速移植物的整合，从而缩短移植物能够支持牙种植体的时间。
