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

Abstract

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.

Signaling pathways of dental implants’ osseointegration: a narrative review on two of the most relevant; NF-κB and Wnt pathways

“…At day 14, all peri-implant cells showed evidence of osteogenic differentiation and mineralization. At the same time point, lateral stability testing confirmed that the L-Wnt3A treated cases have stiffer interface than the control group [89].…”

Twelve‐month evaluation of a novel mineral–organic adhesive material used to stabilize dental implants placed in oversized osteotomies in vivo in an animal model

“…The animals were allowed to heal, and 3 months later, the oversized osteotomies were prepared, and implants placed. This model has been used in different animal models and with different materials (Coelho et al, 2013; Coyac et al, 2020; Lima Bueno et al, 2020). In the case of the negative control (no material around the implant) or the implants with bone xenograft around them, the implant was placed in the osteotomy first.…”

Changes in implant stability using different site preparation techniques: Osseodensification drills versus piezoelectric surgery. A multi‐center prospective randomized controlled clinical trial

“…The early stage of bone repair response after dental implant insertion is a complex phenomenon in which the combined action of inflammatory cascade and immune system regulate new bone formation and neo‐angiogenesis 1 . Among various factors influencing the healing process, excessive implant micro‐movement may compromise osseointegration by producing large interfacial strains which, especially in low‐quality bone, induce bone resorption and determine fibrous encapsulation of the fixture 2–4 . Therefore, one of the main goals in implant surgery is the achievement of adequate primary stability, which is strictly related to both bone quality and quantity, implant design, and implant site preparation characteristics 5 .…”

“… 1 Among various factors influencing the healing process, excessive implant micro‐movement may compromise osseointegration by producing large interfacial strains which, especially in low‐quality bone, induce bone resorption and determine fibrous encapsulation of the fixture. 2 , 3 , 4 Therefore, one of the main goals in implant surgery is the achievement of adequate primary stability, which is strictly related to both bone quality and quantity, implant design, and implant site preparation characteristics. 5 Implant bed preparation should be performed with minimal trauma to the bone, avoiding overheating, and excessive compression of the cortical layer to prevent an excessive inflammatory phase potentially causing massive bone resorption, delayed healing or implant failure.…”