Autologous bone grafts are commonly used to repair defects in skeletal tissue, however, due to their limited supply there is a clinical need for alternatives. Synthetic ceramics present a promising option but currently lack biological activity to stimulate bone regeneration. One potential approach to address this limitation is the incorporation of immunomodulatory agents. In this study, we investigate the application of microbial stimuli to stimulate bone formation. Three different microbial stimuli were incorporated in a biphasic calcium phosphate (BCP) ceramic: Bacille Calmette-Guérin (BCG), gamma-irradiated Staphylococcus aureus (γi-S. aureus), or γi-Candida albicans (γi-C. Albicans). The constructs were then implanted in both a rabbit posterolateral spinal fusion (PLF) and an intramuscular implant model for 10 weeks and compared to a nonstimulated control construct. For the PLF model, the formation of a bony bridge was evaluated by manual palpation, micro computed tomography, and histology. While complete fusion was not observed, the BCG condition was most promising with higher manual stiffness and almost twice as much bone volume in the central fusion mass compared to the control (9 ± 4.4% bone area vs. 4.6 ± 2.3%, respectively). Conversely, the γi-S. aureus or γi-C. albicans appeared to inhibit bone formation (1.4 ± 1.4% and 1.2 ± 0.6% bone area). Bone induction was not observed in any of the intramuscular implants. This study indicates that incorporating immunomodulatory agents in ceramic bone substitutes can affect bone formation, which can be positive when selected carefully. The readily available and clinically approved BCG showed promising results, which warrants further research for clinical translation.

Background: Lumbar interbody fusion (IF) is a common procedure to fuse the anterior spine. However, a lack of consensus on image-based fusion assessment limits the validity and comparison of IF studies. This systematic review aims to (1) report on IF assessment strategies and definitions and (2) summarize available literature on the diagnostic reliability and accuracy of these assessments. Methods: Two searches were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Search 1 identified studies on adult lumbar IF that provided a detailed description of image-based fusion assessment. Search 2 analyzed studies on the reliability of specific fusion criteria/classifications and the accuracy assessed with surgical exploration. Results: A total of 442 studies were included for search 1 and 8 studies for search 2. Fusion assessment throughout the literature was highly variable. Eighteen definitions and more than 250 unique fusion assessment methods were identified. The criteria that showed most consistent use were continuity of bony bridging, radiolucency around the cage, and angular motion <5°. However, reliability and accuracy studies were scarce. Conclusion: This review highlights the challenges in reaching consensus on IF assessment. The variability in IF assessment is very high, which limits the translatability of studies. Accuracy studies are needed to guide innovations of assessment. Future IF assessment strategies should focus on the standardization of computed tomography-based continuity of bony bridging. Knowledge from preclinical and imaging studies can add valuable information to this ongoing discussion.