Osteogenesis imperfect (OI) is a geno- and phenotypically heterogeneous group of congenital collagen disorders characterized by fragility and microfractures resulting in long bone deformities. OI can lead to progressive femoral coxa vara from bone and muscular imbalance and continuous microfracture about the proximal femur. If left untreated, patients develop Trendelenburg gait, leg length discrepancy, further stress fracture and acute fracture at the apex of the deformity, impingement and hip joint degeneration. In the OI patient, femoral coxa vara cannot be treated in isolation and consideration must be given to protecting the whole bone with the primary goal of verticalization and improved biomechanical stability to allow early loading, safe standing, re-orientation of the physis and avoidance of untreated sequelae. Implant constructs should therefore be designed to accommodate and protect the whole bone. The normal paediatric femoral neck shaft angle (FNSA) ranges from 135 to 145 degrees. In OI the progressive pathomechanical changes result in FNSA of significantly less than 120 degrees and decreased Hilgenreiner epiphyseal angles (HEA). Proximal femoral valgus osteotomy is considered the standard surgical treatment for coxa vara and multiple surgical techniques have been described, each with their associated complications. In this paper we present the novel technique of controlling femoral version and coronal alignment using a tubular plate and long bone protection with the use of teleoscoping rods. After the decision to operate had been made, a CT scan of the femur was performed. A 1:1 scale 3D printed model (AXIAL3D, Belfast, UK) was made from the CT scan to allow for accurate implant templating and osteotomy planning. In all cases a subtrochanteric osteotomy was performed and fixed using a pre-bent 3.5 mm 1/3 tubular plate. The plate was bent to allow one end to be inserted into the proximal femur to act as a blade. A channel into the femoral neck was opened using a flat osteotome. The plate was then tapped into the femoral neck to the predetermined position. The final position needed to allow one of the plate holes to accommodate the growing rod. This had to be determined pre operatively using the 3D printed model and the implants. The femoral canal was reamed, and the growing rod was placed in the femur, passing through the hole in the plate to create a construct that could effectively protect both the femoral neck and the full length of the shaft. The distal part of the plate was then fixed to the shaft using eccentric screws around the nail to complete the construct.Introduction
Methodology
Recapitulating tissue elasticity can direct mesenchymal stromal cell (MSC) differentiation; however, it is unclear how substrate elasticity affects MSC metabolism. It is hypothesized MSCs subjected to stiffnesses, atypical of standard tissue culture plastic, display altered metabolic phenotypes during differentiation. In this study, such alterations in MSC metabolic profiles, based on the fluorescence lifetime of NAD(P)H, a critical co-factor in energy production, were monitored using Fluorescence lifetime imaging microscopy (FLIM) as an evaluation tool. Polyacrylamide substrates with varying stiffnesses were fabricated to model the native elasticity of cartilage and bone. MSCs cultured on these substrates exhibited potent alterations in their metabolic status over a 14-day period that were detectable as early as day 3 using FLIM. Overall, soft substrates induced a more glycolytic response after 10 days of culture that persisted at day 14 (as measured by protein-bound NAD(P)H contributions to the lifetime decay). Similarly, by day 10; MSCs on intermediate-stiffness substrates favoured glycolysis. MSCs on stiffer substrates initially displayed a glycolytic phenotype followed by a transition to oxidative phosphorylation by day 10. Staining for mineralised nodules and glycosaminoglycans verified MSCs on stiffer substrates differentiating towards an osteogenic lineage, while MSCs on intermediate substrates showed similarities with differentiated chondrocytes. Overall, it can be concluded that matrix stiffness can induce metabolic perturbations in MSCs for up to 14 days. From this research, ideal culture conditions in which the metabolics of MSCs could be manipulated to promote maximum potency could potentially be defined in the future.
