Probiotics: Can it modulate fracture healing?

OBJECTIVE: Fractures remain a huge burden and their management adversely affects individuals' function and productivity during the lengthy healing period. Gut microbiota exerts a systemic influence on diverse aspects of host physiology, including bone. The primary objective of this study was to evaluate if oral probiotic treatment before or after a fracture in a mouse model could increase cytokines and biomarkers essential for bone healing with subsequent improvement in the biomechanical properties of the healed callus. METHODS: Femoral osteotomy and intramedullary pinning were performed on C57BL/6 mice. Group 1 received either control PBS or probiotic via oral gavage for 5 weeks before fracture (pre-fracture). Group 2 received equivalent treatments for 4 weeks only after fracture (post-fracture). Fracture calluses were harvested on day 3 and 7 for RT-qPCR to quantify osteogenic-related inflammatory cytokines and bone biomarkers. Fractured femurs were evaluated day 28 post-osteotomy via microstructural analysis (µCT) and biomechanical testing (torsion). RESULTS: Mice treated with probiotics pre-fracture (group 1) showed significantly increased gene expression on day 3 of cytokines TGF-ß, IL-6 and IL-17F and a corresponding increase in gene expression on day 7 for Col1 and Runx2. Significant improvement was also seen in bone volume fraction, bone mineral density, tissue mineral density, maximum yield torque, stiffness and strain energy. Mice treated with probiotics post-fracture (group 2), demonstrated no changes in cytokine or bone marker gene expression with no significant changes on microstructural analysis. However, significant increases were seen in twist angle at failure and strain energy, with a corresponding reduction in torsional stiffness. CONCLUSION: Our results suggest that oral probiotic administration, before or after a fracture, may sufficiently alter the gut flora microenvironment leading to improved bone healing biomechanical properties. The use of probiotics may provide a cost-effective and low-risk adjunctive therapy to improve fracture healing.

Is three-point fixation needed to mechanically stabilize zygomaticomaxillary complex fractures?

Fixation is critical in zygomaticomaxillary complex (ZMC) fractures to avoid malunion; however, controversy exists as to how much hardware is required to achieve adequate stability. Current fixation regimens may not represent the minimum stabilization needed for uneventful healing. Craniomaxillofacial (CMF) computational models have shown limited load transmission through the infraorbital rim (IOR), and a previous experimental study of ZMC fractures has suggested that IOR plating does not alter CMF bone strain patterns. This study aimed to measure the impact of stabilization on fracture site displacement under muscle loading, testing the hypothesis that three-point fixation is not critical for ZMC fracture stability. Four ZMC complex fractures were simulated on two cadaveric samples and stabilized with three-point plating. Displacements simulating mouth openings of 20 mm and 30 mm were applied to the mandible using a custom apparatus. Fracture gap displacement under load was measured at multiple points along each fracture line, and bone strain was captured using a combination of uniaxial and rosette gauges. Data capture was repeated with the IOR plate removed (two-point fixation) and with the zygomaticomaxillary plate removed (one-point fixation). Fracture displacement under muscle loading was consistent, with gaps of less than 1 mm in 95% of cases (range 0.05-1.44 mm), reflecting clinical stability. Large variabilities were observed in the strain measurements, which may reflect the complexity of CMFS load patterns and the sensitivity of strain values to gauge placement. This study supports the concept of hardware reduction, suggesting that two-point (or even one-point) fixation may provide sufficient stability for a ZMC fracture under applied muscle loading.

Pilot Study of Optical Topographic Imaging Based Neuronavigation for Mastoidectomy.

BACKGROUND: Mastoidectomy involves drilling the temporal bone while avoiding the facial nerve, semicircular canals, sigmoid sinus, and tegmen. Optical topographic imaging (OTI) is a novel registration technique that allows rapid registration with minimal navigational error. To date, no studies have examined the use of OTI in skull-base procedures. METHODS: In this cadaveric study, 8 mastoidectomies were performed in 2 groups-4 free-hand (FH) and 4 OTI-assisted mastoidectomies. Registration accuracy for OTI navigation was quantified with root mean square (RMS) and target registration error (TRE). Procedural time, percent of mastoid resected, and the proximity of the mastoidectomy cavity to critical structures were determined. RESULTS: The average RMS and TRE associated with OTI-based registration were 1.44 mm (±0.83 mm) and 2.17 mm (±0.89 mm), respectively. The volume removed, expressed as a percentage of the total mastoid volume, was 37.5% (±10.2%) versus 31.2% (±2.3%), P = 0.31, for FH and OTI-assisted mastoidectomy. There were no statistically significant differences between FH and OTI-assisted mastoidectomies with respect to proximity to critical structures or procedural time. CONCLUSIONS: This work is the first examining the application of OTI neuronavigation in lateral skull-base procedures. This pilot study revealed the RMS and TRE for OTI-based navigation in the lateral skull base are 1.44 mm (±0.83 mm) and 2.17 mm (±0.89 mm), respectively. This pilot study demonstrates that an OTI-based system is sufficiently accurate and may address barriers to widespread adoption of navigation for lateral skull-base procedures.

Bullseye EVD: preclinical evaluation of an intra-procedural system to confirm external ventricular drainage catheter positioning.

PURPOSE: External ventricular drainage (EVD) is a life-saving procedure indicated for elevated intracranial pressure. A catheter is inserted into the ventricles to drain cerebrospinal fluid and release the pressure on the brain. However, the standard freehand EVD technique results in catheter malpositioning in up to 60.1% of procedures. This proof-of-concept study aimed to evaluate the registration accuracy of a novel image-based verification system "Bullseye EVD" in a preclinical cadaveric model of catheter placement. METHODS: Experimentation was performed on both sides of 3 cadaveric heads (n = 6). After a pre-interventional CT scan, a guidewire simulating the EVD catheter was inserted as in a clinical EVD procedure. 3D structured light images (Einscan, Shining 3D, China) were acquired of an optical tracker placed over the guidewire on the surface of the scalp, along with three distinct cranial regions (scalp, face, and ear). A computer vision algorithm was employed to determine the guidewire position based on the pre-interventional CT scan and the intra-procedural optical imaging. A post-interventional CT scan was used to validate the performance of the Bullseye optical imaging system in terms of trajectory and offset errors. RESULTS: Optical images which combined facial features and exposed scalp within the surgical field resulted in the lowest trajectory and offset errors of 1.28° ± 0.38° and 0.33 ± 0.19 mm, respectively. Mean duration of the optical imaging procedure was 128 ± 35 s. CONCLUSIONS: The Bullseye EVD system presents an accurate patient-specific method to verify freehand EVD positioning. Use of facial features was critical to registration accuracy. Workflow automation and development of a user interface must be considered for future clinical evaluation.

Can CD200R1 Agonists Slow the Progression of Osteoarthritis Secondary to Injury?

Post-traumatic knee osteoarthritis is characterized by cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes. Therapeutic targeting of inflammatory activity in the knee immediately post injury may alter the course of osteoarthritis development. This study aimed to determine whether CD200R1 agonists, namely the protein therapeutic CD200Fc or the synthetic DNA aptamer CCS13, both known to act as anti-inflammatory agents, are able to delay the pathogenesis of injury-associated knee osteoarthritis in a murine model. Ten week old male C57BL/6 mice were randomized and surgical destabilization of the medial meniscus (DMM) to induce knee arthritis or sham surgery as a control were performed. CCS13 was evaluated as a therapeutic treatment along with CD200Fc and a phosphate-buffered saline vehicle control. Oligonucleotides were injected intra-articularly beginning one week after surgery, with a total of six injections administered prior to sacrifice at 12 weeks post-surgery. Histopathological assessment was used as the primary outcome measure to assess cartilage and synovial changes, while µCT imaging was used to compare the changes to the subchondral bone between untreated and treated arthritic groups. We did not find any attenuation of cartilage degeneration or synovitis in DMM mice with CD200Fc or CCS13 at 12 weeks post-surgery, nor stereological differences in the properties of subchondral bone. The use of CD200R1 agonists to blunt the inflammatory response in the knee are insufficient to prevent disease progression in the mouse DMM model of OA without anatomical restoration of the normal joint biomechanics.