Bioactivating a bone substitute accelerates graft incorporation in a murine model of vertical ridge augmentation

Abstract

ObjectiveCompared 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. MethodsWild-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. ResultsTunneling 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. SignificanceLocal 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.