Biology of sinus floor augmentation with an autograft versus a bone graft substitute in a preclinical in vivo experimental model

Abstract

Objectives Compared to autografts, bone graft substitutes are slower to consolidate. If we understood why, this might open strategies to accelerate new bone formation and thus shorten the time to implant placement. In this study, we aimed at comparing autologous bone graft with a bovine bone graft substitute in a preclinical sinus lift model. Materials and Methods The mouse posterior paranasal sinus served as a recipient site for grafting. Autograft from the oral cavity was compared against bone graft substitute using molecular, cellular, and histological analyses conducted on post‐grafting days (PSD) 0, 9, 18, and 120. Results Either autografts or bone graft substitutes were positioned on the sinus floor and remained in situ throughout the study. At the time of grafting and until day 9, bone graft substitutes were devoid of cells and alkaline phosphatase (ALP) activity while autografts were comprised of viable cells and showed strong ALP (mineralization) activity. Consequently, new bone formed faster in autografts compared to bone graft substitutes (140.21 ± 41.21 µm vs. 41.70 ± 10.09 µm, respectively, PSD9, p = .0143). By PSD18, osteogenesis was evident in autografted and xenografted sites. Osteoclasts identified by tartrate resistant acid phosphatase attached to, but did not resorb the bone graft substitute matrix. Autograft matrix, however, underwent extensive resorption. Transgenic mice revealed that Wnt‐responsive osteoprogenitor cells originated primarily from the internal periosteum of the maxillary bone, and not from the Schneiderian membrane. Conclusion Autografts produce new bone sooner, but bovine bone graft substitutes eventually consolidate and then resist resorption. Enhancing osteoprogenitor cell recruitment to a bone graft substitute constitutes a viable strategy for accelerating bone formation in a sinus lift procedure.

Insights into skeletal stem cells

“…Internal periosteum-derived Wnt-responsive progenitors of the maxillary bone was found to contribute to new bone formation. 167 …”

A WNT protein therapeutic accelerates consolidation of a bone graft substitute in a pre‐clinical sinus augmentation model

“…Because they do not contain cells, new bone formation around bovine BGSs was solely dependent upon the recruitment of osteoprogenitor cells from the local environment, followed by their differentiation into matrix‐secreting osteoblasts (Figure 2 and see Coyac et al, 2021).…”

“…We provide insights into the basis for this slower rate of consolidation by demonstrating that autografts contain osteoprogenitor cells, whereas BGSs must recruit osteoprogenitor cells from native bone. While they may consolidate faster, autografts also tend to show greater resorption (Coyac et al, 2021). Here we provide evidence that this resorption diminishes implant support.…”

“…This is the rate-limiting step when a BGS is employed (Figure 3); consequently, our therapeutic approach was focused on accelerating the rate of consolidation. Having identified a source of osteoprogenitor cells, that is, from the maxillary internal periosteum (Appendix Figure 2), and demonstrating that these osteoprogenitor cells were responsive to a WNT stimulus (Coyac et al, 2021), we tested whether combining WNT3A protein with a BGS would render the combination product osteoinductive.…”

Sinus Augmentation for Implant Placement Utilizing a Novel Synthetic Graft Material with Delayed Immediate Socket Grafting: A 2-Year Case Study

“…Various materials have been advocated and utilized falling into the categories of allograft, xenograft and synthetic materials. Each category has been well documented for the utilization in sinus augmentation procedures in the literature [ 1 , 2 , 3 ]. Several factors weigh in decisions when selecting a type of osseous graft material.…”