OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Mary L Bouxsein; Stephen K Boyd; Blaine A Christiansen; Robert E Guldberg; Karl J Jepsen; Ralph Müller Journal: J Bone Miner Res Date: 2010-07 Impact factor: 6.741
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Authors: Esther Cory; Ara Nazarian; Vahid Entezari; Vartan Vartanians; Ralph Müller; Brian D Snyder Journal: J Biomech Date: 2009-12-08 Impact factor: 2.712
Authors: Monica Florio; Kannan Gunasekaran; Marina Stolina; Xiaodong Li; Ling Liu; Barbara Tipton; Hossein Salimi-Moosavi; Franklin J Asuncion; Chaoyang Li; Banghua Sun; Hong Lin Tan; Li Zhang; Chun-Ya Han; Ryan Case; Amy N Duguay; Mario Grisanti; Jennitte Stevens; James K Pretorius; Efrain Pacheco; Heidi Jones; Qing Chen; Brian D Soriano; Jie Wen; Brenda Heron; Frederick W Jacobsen; Emil Brisan; William G Richards; Hua Zhu Ke; Michael S Ominsky Journal: Nat Commun Date: 2016-05-27 Impact factor: 14.919