Intravital longitudinal imaging of peri-implant endosseous wound healing reveals the role of nanosurfaces in regulating neovascular morphogenesis in vivo

Khosravi, Niloufar (Faculty of Dentistry, University of Toronto)
Maeda, Azusa (University Health Network, Toronto, ON)
DaCosta, Ralph S (University Health Network, Toronto, ON)
Davies, John E (Faculty of Dentistry, University of Toronto)

Introduction

Nanosurfaces have improved the clinical success rate of implants by increasing the rate at which osseointegration is achieved. However, the modulating effect of these complex surfaces during the early healing is not fully understood at the cellular level. Neovascularization is considered an essential prerequisite to osteogenesis as the mesenchymal progenitors of osteogenic cells have a perivascular origin. Thus, our aim is to examine the effect of nanosurfaces on the spatiotemporal pattern of neovascularization in vivo during peri-implant wound healing.

Materials and Methods

We developed a new experimental model that integrates a custom-designed murine cranial metallic implant with an optically transparent window chamber compatible with both confocal- or multiphoton-based imaging systems. We tracked the neovascularization and osteogenesis in the peri-implant wound site over clinically relevant time scales, from day 3 to 42 post-implantation as a function of implant topography. The 3D Morphometric analysis was performed to characterize the neovasculature over time.

Results

Microvascular density around the nano surface (NT) was significantly higher than the machined surface (MA) at day 7 (shown in the figure), 11, and 28 post-implantation. 3D analysis of the vascular network revealed that the nano surface contributes to the development of a radially arranged vascular structure with hierarchical branches spatially closer to the surface of the Ti-implant. Further µCT assessment of the bone formation showed contact osteogenesis in the healing volumes around the nanosurface. However, the nonmodified MA surface only exhibited distance osteogenesis.

Discussion and Conclusion

Nanosurfaces not only increased the rate of neovascularization, but also changed the organization, the spatial pattern, and the architecture of the re-established microvasculature following endosseous implantation that resulted in a change in the mechanism of peri-implant bone healing from distance to contact osteogenesis. The knowledge transferred from the current study provides one step forward towards designing endosseous implants capable of overcoming delayed peri-implant wound healing through controlling endogenous vascularization.


Acknowledgements

Advanced Optical Microscopy Facility (UHN), Animal Resources Center (UHN), Zimmer-Biomet Dental Inc, Canadian Institutes of Health Research (CIHR)

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