Bone Morphology and Vascular Supply of Pedicled Distal Radius Bone Using Nano-Computed Tomography.

BACKGROUND: The goal of this study was to use nano-computed tomography to describe the intraosseous vascularity and structural characteristics of commonly used distal radius vascularized bone grafts for treatment of scaphoid nonunion. METHODS: We obtained 8 fresh frozen human cadaver forearm specimens for infusion of barium contrast. Specimens were scanned and segmented to quantify the vascular volume and trabecular density within 3 common graft regions, including 1, 2 intercompartmental supraretinacular artery (1,2 ICSRA), fourth extensor compartment artery (4 ECA), and volar carpal artery (VCA), as well as thirds of the scaphoid. Outcomes also included mean and maximum cortical thickness and number of cortical perforators. Single-specimen analyses were also performed comparing vascularity and trabecular density of each graft with scaphoid regions of a single specimen. Statistical analysis was performed using analysis of variance with post hoc Tukey testing when P value was less than .05. RESULTS: There was no significant difference between groups in the mean percent vascularity (P = .76). The ratio of trabecular bone in each graft to scaphoid thirds was less than 1. The mean cortical thickness (0.79 mm, 95% confidence interval [CI], 0.66-0.93 mm) and maximum cortical thickness (1.45 mm, 95% CI, 1.27-1.63 mm) of VCA grafts were both significantly greater than those of 4 ECA and 1,2 ICSRA (P < .001). CONCLUSIONS: There were no differences between vascular density of the 3 grafts and the scaphoid. Pedicled distal radius bone grafts have similar vascularity but morphometric differences such as cortical thickness and trabecular density which have unclear clinical implications.

Biomechanical Comparison of a Novel Multiplanar, Perpendicular Whipstitch With the Krackow Stitch and Standard Commercial Whipstitch.

Background: Using alternating orthogonal suture throws with the looped whipstitch technique may allow enhanced suture fixation. Hypothesis: It was hypothesized that this novel multiplanar, perpendicular looped whipstitch (MP) technique would have improved biomechanical properties compared with the standard looped whipstitch (WS) and Krackow stitch (KS). Study Design: Controlled laboratory study. Methods: A total of 30 cadaveric tibialis anterior tendons were randomly assigned into 3 groups of 10. Tendons were secured to a custom clamp, and the other end was sutured using 1 of 3 techniques: the KS, WS, or novel MP. The MP was performed with alternating orthogonal throws starting right to left, then front to back, left to right, and back to front. Each technique used 4 passes of No. 2 FiberWire spaced 5 mm apart and ending 10 mm from the tendon end. Tendons were preloaded to 5 N, pretensioned to 50 N at 100 mm/min for 3 cycles, returned to 5 N for 1 minute, cycled from 5 to 100 N at 200 mm/min for 100 cycles, and then loaded to failure at 20 mm/min. Elongation was recorded after pretensioning and cycling and was measured both across the suture-tendon interface and from the base of the suture-tendon interface to markings on the suture limbs (construct elongation). One-way analyses of variance were performed, with Bonferroni post hoc analysis when appropriate. Results: There were no differences in cross-sectional area or stiffness among the 3 techniques. The ultimate load for WS (183.33 ± 57.44 N) was less compared with both MP (270.76 ± 39.36 N) and KS (298.90 ± 25.94 N) (P ≤ .001 for both). There was less construct elongation for KS compared with WS and MP for total displacement, measured from pretensioning to the end of cycling (P < .001). All 3 techniques saw a decrease in length (shortening) at the suture-tendon interface during testing. There was more shortening at the suture-tendon interface for WS compared with KS (P = .006). Conclusion: The KS appears superior, as it maximized strength while minimizing construct elongation or graft shortening. The ultimate load of the MP technique was greater than that of the standard technique but not significantly different from that of the KS technique. Clinical Relevance: The KS is preferred. If using a WS, multiplanar, perpendicular passes should be considered.

Novel Lineage-Tracing System to Identify Site-Specific Ectopic Bone Precursor Cells.

Heterotopic ossification (HO) is a form of pathological cell-fate change of mesenchymal stem/precursor cells (MSCs) that occurs following traumatic injury, limiting range of motion in extremities and causing pain. MSCs have been shown to differentiate to form bone; however, their lineage and aberrant processes after trauma are not well understood. Utilizing a well-established mouse HO model and inducible lineage-tracing mouse (Hoxa11-CreERT2;ROSA26-LSL-TdTomato), we found that Hoxa11-lineage cells represent HO progenitors specifically in the zeugopod. Bioinformatic single-cell transcriptomic and epigenomic analyses showed Hoxa11-lineage cells are regionally restricted mesenchymal cells that, after injury, gain the potential to undergo differentiation toward chondrocytes, osteoblasts, and adipocytes. This study identifies Hoxa11-lineage cells as zeugopod-specific ectopic bone progenitors and elucidates the fate specification and multipotency that mesenchymal cells acquire after injury. Furthermore, this highlights homeobox patterning genes as useful tools to trace region-specific progenitors and enable location-specific gene deletion.

Immobilization after injury alters extracellular matrix and stem cell fate.

Cells sense the extracellular environment and mechanical stimuli and translate these signals into intracellular responses through mechanotransduction, which alters cell maintenance, proliferation, and differentiation. Here we use a mouse model of trauma-induced heterotopic ossification (HO) to examine how cell-extrinsic forces impact mesenchymal progenitor cell (MPC) fate. After injury, single-cell (sc) RNA sequencing of the injury site reveals an early increase in MPC genes associated with pathways of cell adhesion and ECM-receptor interactions, and MPC trajectories to cartilage and bone. Immunostaining uncovers active mechanotransduction after injury with increased focal adhesion kinase signaling and nuclear translocation of transcriptional coactivator TAZ, inhibition of which mitigates HO. Similarly, joint immobilization decreases mechanotransductive signaling, and completely inhibits HO. Joint immobilization decreases collagen alignment and increases adipogenesis. Further, scRNA sequencing of the HO site after injury with or without immobilization identifies gene signatures in mobile MPCs correlating with osteogenesis, and signatures from immobile MPCs with adipogenesis. scATAC-seq in these same MPCs confirm that in mobile MPCs, chromatin regions around osteogenic genes are open, whereas in immobile MPCs, regions around adipogenic genes are open. Together these data suggest that joint immobilization after injury results in decreased ECM alignment, altered MPC mechanotransduction, and changes in genomic architecture favoring adipogenesis over osteogenesis, resulting in decreased formation of HO.