The Effects of Dynamic Loading on Bone Fracture Healing Under Ilizarov Circular Fixators.

Early weight bearing appears to enhance bone fracture healing under Ilizarov circular fixators (ICFs). However, the role of early weight bearing in the healing process remains unclear. This study aims to provide insights into the effects of early weight bearing on healing of bone fractures stabilized with ICFs, with the aid of mathematical modeling. A computational model of fracture site was developed using poro-elastic formulation to simulate the transport of mesenchymal stem cells (MSCs), fibroblasts, chondrocytes, osteoblasts, osteogenic growth factor (OGF), and chondrogenic growth factor (CGF) and MSC differentiation during the early stage of healing, under various combinations of fracture gap sizes (GS), ICF wire pretension forces, and axial loads. 1 h of physiologically relevant cyclic axial loading followed by 23 h of rest in the post-inflammation phase (i.e., callus with granulation tissue) was simulated. The results show that physiologically relevant dynamic loading could significantly enhance cell and growth factor concentrations in the fracture site in a time and spatially dependent manner. 1 h cyclic loading (axial load with amplitude, PA, of 200 N at 1 Hz) increased the content of chondrocytes up to 37% (in all zones of callus), CGF up to 28% (in endosteal and periosteal callus) and OGF up to 50% (in endosteal and cortical callus) by the end of the 24 h period simulated. This suggests that the synergistic effect of dynamic loading-induced advective transport and mechanical stimuli due to early weight bearing is likely to enhance secondary healing. Furthermore, the study suggests that relatively higher PA values or lower ICF wire pretension forces or smaller GS could result in increased chondrocyte and GF content within the callus.

Influence of muscle loading on early-stage bone fracture healing.

Designing weight-bearing exercises for patients with lower-limb bone fractures is challenging and requires a systematic approach that accounts for patient-specific loading conditions. However, 'trial-and-error' approaches are commonplace in clinical settings due to the lack of a fundamental understanding of the effect of weight-bearing exercises on the bone healing process. Whilst computational modelling has the potential to assist clinicians in designing effective patient-specific weight-bearing exercises, current models do not explicitly account for the effects of muscle loading, which could play an important role in mediating the mechanical microenvironment of a fracture site. We combined a fracture healing model involving a tibial fracture stabilised with a locking compression plate (LCP) with a detailed musculoskeletal model of the lower limb to determine interfragmentary strains in the vicinity of the fracture site during both full weight-bearing (100% body weight) and partial weight-bearing (50% body weight) standing. We found that muscle loading significantly altered model predictions of interfragmentary strains. For a fractured bone with a standard LCP configuration (bone-plate distance = 2 mm, working length = 30 mm) subject to full weight-bearing, the predicted strains at the near and far cortices were 23% and 11% higher when muscle loading was included compared to the case when muscle loading was omitted. The knee and ankle muscles accounted for 38% of the contact force exerted at the knee joint during quiet standing and contributed significantly to the strains calculated at the fracture site. Thus, models of bone fracture healing ought to account explicitly for the effects of muscle loading. Furthermore, the study indicated that LCP configuration parameters play a crucial role in influencing the fracture site microenvironment. The results highlighted the dominance of working length over bone-plate distance in controlling the flexibility of fracture sites stabilised with LCP devices.

Optimal time-dependent levels of weight-bearing for bone fracture healing under Ilizarov circular fixators.

It is known that weight-bearing exercises under Ilizarov circular fixators (ICF) could enhance bone fracture healing by mechano-regulation. However, interfragmentary movements at the fracture site induced by weight-bearing may inhibit angiogenesis and ultimately delay the healing process. To tackle this challenge, a computational model is presented in this study which considers the spatial and temporal changes in mechanical properties of fracture callus to predict optimal levels of weight-bearing during fracture healing under ICF. The study takes sheep fractures as example and shows that the developed model has the capability of predicting patient specific, time-dependent optimal levels of weight-bearing which enhances mechano-regulation mediated healing without hindering the angiogenesis process. The results demonstrate that allowable level of weight-bearing and timings depend on fracture gap size. For normal body weights (BW) and moderate fracture gap sizes (e.g. 3 mm), weight-bearing with 30% BW could start by week 4 post-operation and gradually increase to 100% BW by week 11. In contrast, for relatively large fracture gap sizes (i.e. 6 mm), weight-bearing is recommended to commence in later stages of healing (e.g. week 11 post-operation). Furthermore, increasing ICF stiffness (e.g. using half pins instead of pretension wires) can increase the level of weight-bearing significantly in the early stages up to a certain time point (e.g. week 8 post-operation) beyond which no noticeable benefits could be achieved. The findings of this study have potential applications in designing post-operative weight bearing exercises.

A probabilistic approach for modelling bone fracture healing under Ilizarov circular fixator.

Bone fracture treatments using Ilizarov circular fixator (ICF) involve dealing with uncertainties about a range of critical factors that control the mechanical microenvironment of the fracture site such as ICF configuration, fracture gap size, physiological loading etc. To date, the effects of the uncertainties about these critical factors on the mechanical microenvironment of the fracture site have not been fully understood. The purpose of this study is to tackle this challenge by using computational modelling in conjunction with engineering reliability analysis. Particularly, the effects of uncertainties in fracture gap size (GS), level of weight-bearing (P), ICF wire pretension (T) and wire diameter (WD) on the fracture site mechanical microenvironment at the beginning of the reparative phase of healing was investigated in this study. The results show that the mechanical microenvironment of fracture site stabilised with ICF is very sensitive to the uncertainties in P and GS. For example, an increase in the coefficient of variation of P (COVP ) from 0.1 to 0.9 (i.e., an increase in the uncertainty in P) could reduce the probability of achieving a favourable mechanical microenvironment within the fracture site (i.e., Probability of Success, PoS) by more than 50%, while an increase in the coefficient of variation of GS (COVGS ) from 0.1 to 0.9 could decrease PoS by around 30%. In contrast, an increase in the uncertainties in T and WD (COV increase from 0.1 to 0.9) has little influence on the fracture site mechanical microenvironment (PoS changes <5%).

Bone fracture healing under Ilizarov fixator: Influence of fixator configuration, fracture geometry, and loading.

This study aims to enhance the understanding of the relationship between Ilizarov fixator configuration and its effects on bone fracture healing. Using Taylor spatial frame (TSF) as an example, the roles of critical parameters (ie, TSF ring diameter, wire pre-tension, fracture gap size, and axial load) that govern fracture healing during the early stages were investigated by using computational modelling in conjunction with mechanical testing involving an advanced 3D optical measurement system. The computational model was first validated using the mechanical test results and then used to simulate mesenchymal stem cell (MSC) differentiations within different regions of the fracture site under various combinations of TSF ring diameter, wire pre-tension, fracture gap size, and axial load values. Predicted spatially dependent MSC differentiation patterns and the influence of each parameter on differentiations were compared with in vivo results, and good agreement was seen between the two. Gap size was identified as the most influential parameter in MSC differentiation, and the influence of axial loading and TSF configuration (ie, ring diameter and wire pre-tension) on cell differentiation was seen to be gap size dependent. Most changes in cell differentiation were predicted in the external callus (periosteal), which is the crucial region of the callus in the early stages. However, for small gap sizes (eg, 1 mm), significant changes were predicted in the endosteal callus as well. The study exhibits the potential of computational models in assessing the performance of Ilizarov fixators as well as assisting surgeons in patient-specific clinical treatment planning.