Autologous chondrocyte grafting promotes bone formation in the posterolateral spine

Abstract

Background context Pseudarthrosis following spinal fusion remains problematic despite modern surgical and grafting techniques. In surgical spinal fusion, new bone forms via intramembranous and endochondral ossification, with endochondral ossification occurring in the hypoxic zones of the fusion bed. During bone development and fracture healing, the key cellular mediator of endochondral ossification is the hypertrophic chondrocyte given its ability to function in hypoxia and induce neovascularization and ossification. We therefore hypothesize that hypertrophic chondrocytes may be an effective bone graft alternative. Purpose Spinal fusion procedures have increased substantially; yet 5% to 35% of all spinal fusions may result in pseudoarthrosis. Pseudoarthrosis may occur because of implant failure, infection, or biological failure, among other reasons. Advances in surgical techniques and bone grafting have improved fusion; however pseudarthrosis rates remain unacceptably high. Thus, the goal of this study is to investigate hypertrophic chondrocytes as a potential biological graft alternative. Methods Using a validated murine fracture model, hypertrophic chondrocytes were harvested from fracture calluses and transplanted into the posterolateral spines of identical mice. New bone formation was assessed by X‐ray, microcomputed tomography (μCT), and in vivo fluorescent imaging. Results were compared against a standard iliac crest bone graft and a sham surgery control group. Funding for this work was provided by the Department of Orthopaedics and Rehabilitation, the OREF (Grant #16‐150), and The Caitlin Lovejoy Fund. Results Radiography, μCT, and in vivo fluorescent imaging demonstrated that hypertrophic chondrocytes promoted bone formation at rates equivalent to iliac crest autograft. Additionally, μCT analysis demonstrated similar fusion rates in a subset of mice from the iliac crest and hypertrophic chondrocyte groups. Conclusions This proof‐of‐concept study indicates that hypertrophic chondrocytes can promote bone formation comparable to iliac crest bone graft. These findings provide the foundation for future studies to investigate the potential therapeutic use of hypertrophic chondrocytes in spinal fusion.

Cyclic Tensile Stress to Rat Thoracolumbar Ligamentum Flavum Inducing the Ossification of Ligamentum Flavum

“…Therefore, we consider that RUNX-2 has the potential to be a sensitive indicator of dynamically monitoring the OLF process. OPN accelerates the neovascularization and osteogenic differentiation of ligament fibroblasts by interacting with VEGF, CD44, and integrin β3 27–29 . The above mechanisms together play a major role in the OLF generated by tension.…”

“…OPN accelerates the neovascularization and osteogenic differentiation of ligament fibroblasts by interacting with VEGF, CD44, and integrin b3. [27][28][29] The above mechanisms together play a major role in the OLF generated by tension.…”

Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

“…As mentioned before, hypertrophic chondrocytes within the fracture callus stimulate osteogenesis and vasculogenesis during bone fracture healing, and hypertrophic chondrocytes isolated from fracture calluses, even from callus tissue directly, have demonstrated the capacity to promote bone regeneration. 69 , 70 These inherent biological features suggest that the use of hypertrophic chondrocytes is a logical therapeutic strategy for bone regeneration.…”