Bone formation around unstable implants is enhanced by a WNT protein therapeutic in a preclinical in vivo model.

Benjamin R Coyac, Brian Leahy, Zhijun Li, Giuseppe Salvi, Xing Yin, John B Brunski, Jill A Helms

Clinical oral implants research 2020 Nov

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Our objective was to test the hypothesis that local delivery of a WNT protein therapeutic would support osseointegration of an unstable implant placed into an oversized osteotomy and subjected to functional loading. Using a split-mouth design in an ovariectomized (OVX) rat model, 50 titanium implants were placed in oversized osteotomies. Implants were subjected to functional loading. One-half of the implants were treated with a liposomal formulation of WNT3A protein (L-WNT3A); the other half received an identical liposomal formulation containing phosphate-buffered saline (PBS). Finite element modeling estimated peri-implant strains caused by functional loading. Histological, molecular, cellular, and quantitative micro-computed tomographic (µCT) imaging analyses were performed on samples from post-implant days (PID) 3, 7, and 14. Lateral implant stability was quantified at PID 7 and 14. Finite element analyses predicted levels of peri-implant strains incompatible with new bone formation. Micro-CT imaging, histological, and quantitative immunohistochemical (IHC) analyses confirmed that PBS-treated implants underwent fibrous encapsulation. In those cases where the peri-implant environment was treated with L-WNT3A, µCT imaging, histological, and quantitative IHC analyses demonstrated a significant increase in expression of proliferative (PCNA) and osteogenic (Runx2, Osterix) markers. One week after L-WNT3A treatment, new bone formation was evident, and two weeks later, L-WNT3A-treated gaps had a stiffer interface compared to PBS-treated gaps. In a rat model, unstable implants undergo fibrous encapsulation. If the same unstable implants are treated with L-WNT3A at the time of placement, then it results in significantly more peri-implant bone and greater interfacial stiffness. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Citation

Benjamin R Coyac, Brian Leahy, Zhijun Li, Giuseppe Salvi, Xing Yin, John B Brunski, Jill A Helms. Bone formation around unstable implants is enhanced by a WNT protein therapeutic in a preclinical in vivo model. Clinical oral implants research. 2020 Nov;31(11):1125-1137