Understanding the relationship between interfragmentary movement and callus growth in fracture healing: A novel computational approach

Introduction & Aims Optimising fracture treatments requires a sound understanding of relationships between stability, callus development and healing outcomes. This has been the goal of computational modelling, but discrepancies remain between simulations and experimental results. We compared healing patterns vs fixation stiffness between a novel computational callus growth model and corresponding experimental data. Hypothesis We hypothesised that callus growth is stimulated by diffusible signals, whose production is in turn regulated by mechanical conditions at the fracture site. We proposed that introducing this scheme into computational models would better replicate the observed tissue patterns and the inverse relationship between callus size and fixation stiffness. Method Finite element models of bone healing under stiff and flexible fixation were constructed, based on the parameters of a parallel rat femoral osteotomy study. An iterative procedure was implemented, to simulate the development of callus and its mechanical regulation. Tissue changes were regulated according to published mechano-biological criteria. Predictions of healing patterns were compared between standard models, with a pre-defined domain for callus development, and a novel approach, in which periosteal callus growth is driven by a diffusible signal. Production of this signal was driven by local mechanical conditions. Finally, each model’s predictions were compared to the corresponding histological data. Results Models in which healing progressed within a prescribed callus domain predicted that greater interfragmentary movements would displace early periosteal bone formation further from the fracture. This results from artificially large distortional strains predicted near the fracture edge. While experiments showed increased hard callus size under flexible fixation, this was not reflected in the standard models. Allowing the callus to grow from a thin soft tissue layer, in response to a mechanically stimulated diffusible signal, results in a callus shape and tissue distribution closer to those observed histologically. Importantly, the callus volume increased with increasing interfragmentary movement. Conclusions A novel method to incorporate callus growth into computational models of fracture healing allowed us to successfully capture the relationship between callus size and fixation stability observed in our rat experiments. This approach expands our toolkit for understanding the influence of different fixation strategies on healing outcomes

Creation of a validated 3D finite-element model of an ovine tibia

Ovine models are widely used in orthopaedics and trauma research. We present the development and validation of an FE model of an ovine tibia for use in the testing of tibia fracture fixation plates. The FE model was generated from CT data of a cadaveric tibia and validated by mechanical testing of the bone. An offset 3-pt bend test was conducted with strain gauges placed on the anterior and posterior surfaces of the diaphysis. The loads applied during testing were applied to the model after digitising their location and orientation with a 3D digitiser. A comparison of the surface strains was conducted. Initial results show a good correlation between the mechanical test and the FE model with calculated strain values within 2% of the measured strains. Further improvements are expected with the incorporation of bone density-specific material properties in the model

Computational simulation of bone fracture healing under inverse dynamization

Adaptive finite element models have allowed researchers to test hypothetical relationships between the local mechanical environment and the healing of bone fractures. However, their predictive power has not yet been demonstrated by testing hypotheses ahead of experimental testing. In this study, an established mechano-biological scheme was used in an iterative finite element simulation of sheep tibial osteotomy healing under a hypothetical fixation regime, “inverse dynamisation”. Tissue distributions, interfragmentary movement and stiffness across the fracture site were compared between stiff and flexible fixation conditions and scenarios in which fixation stiffness was increased at a discrete time-point. The modelling work was conducted blind to the experimental study to be published subsequently. The simulations predicted the fastest and most direct healing under constant stiff fixation, and the slowest healing under flexible fixation. Although low fixation stiffness promoted more callus formation prior to bridging, this conferred little additional stiffness to the fracture in the first 5 weeks. Thus, while switching to stiffer fixation facilitated rapid subsequent bridging of the fracture, no advantage of inverse dynamisation could be demonstrated. In vivo data remains necessary to conclusively test this treatment protocol and this will, in turn, provide an evaluation of the model’s performance. The publication of both hypotheses and their computational simulation, prior to experimental testing, offers an appealing means to test the predictive power of mechano-biological models

Bone Plate

The bone plate (1) has a lower surface (2), an upper surface (3), a thickness T measured between the lower and upper surfaces (2;3), a longitudinal axis (4) and a plurality of plate holes (5) running from the lower surface (2) to the upper surface (3). The bone plate (1) further has a slot (6) extending from the lower surface (2) towards the upper surface (3) and having a width W measured at the lower surface (2) and parallel to the longitudinal axis (4). The slot (6) extends to a maximum distance D measured from the lower surface (2) towards the upper surface (3) of 0.4 - 0.9 times the thickness T of the bone plate (1). The slot (6) has a width measured parallel to the longitudinal axis (4) which at its maximum extension E is at least 0.8 mm, preferably of at least 3 mm. The slot (6) allows the plate (1) to bend longitudinally - additionally to the intrinsic bendability of the unslotted plate (1) - at most to the amount of 20°, preferably at most to the amount of 10°. Due to the bi-phasic properties of the bone plate (1) optimal bending properties and adaptability to anatomical surfaces are achieved

Biphasic plating – In vivo study of a novel fixation concept to enhance mechanobiological fracture healing

Background: Fracture fixation has advanced significantly with the introduction of locked plating and minimally invasive surgical techniques. However, healing complications occur in up to 10% of cases, of which a significant portion may be attributed to unfavorable mechanical conditions at the fracture. Moreover, state-of-the-art plates are prone to failure from excessive loading or fatigue. A novel biphasic plating concept has been developed to create reliable mechanical conditions for timely bone healing and simultaneously improve implant strength. This paper introduces the novel fixation concept and presents preclinical results from a large animal study. Methods: Twenty-four sheep underwent a mid-diaphyseal osteotomy stabilized with either the novel biphasic plate fixator or a control locking plate. Different fracture patterns regarding orientation and localization were investigated. Animals were free to fully bear weight during the post-operative period. After 12 weeks, the healing fractures were evaluated for bone formation using micro-computer tomography and strength and stiffness using biomechanical testing. Additionally, histological evaluation of soft tissue samples with respect to metal wear debris was performed. Results: No plate deformation or failures were observed under full weight bearing with the biphasic plate. Defects stabilized with the biphasic plate demonstrated robust callus formation compared to control group. Torsion tests after plate removal revealed no statistical difference in peak torsion to failure and stiffness for the different fracture patterns stabilized with the biphasic plate. However, the biphasic plate group specimens were 45% stronger (p=0.002) and 48% stiffer (p=0.007) than the controls. No histological signs of metal wear due to the biphasic feature could be found. Conclusions: The biphasic plate concept is aimed at improving the biomechanics of locked plating. The results of this large animal study demonstrate the feasibility and clinical potential of this novel stabilization concept.</p

Morphology of bony callus growth in healing of a sheep tibial osteotomy

Long bone fractures typically heal via formation of an external callus, which helps stabilise the bone fragments. Callus composition and morphology influence the mechanical environment, which in turn regulates the progression of healing. Therefore characterising callus development over time is crucial in understanding this mechanobiological regulation. Although bony callus is often assumed to grow towards the fracture from either side, this is not consistent with observations from large animal studies and clinical cases. Therefore, we sought to quantify the morphology of bony callus over time in a large animal model.Sheep tibiae were x-rayed weekly over eight weeks following an osteotomy (n=5), with fixation allowing up to 10% axial displacement under normal weight-bearing. After scaling radiographs by known landmarks and normalising greyscales, bony callus boundaries were defined by manual segmentation. The lateral callus area and coordinates of its centroid were calculated from each image.The external callus initially formed adjacent to the osteotomy site. Over the first four weeks, callus growth from its outer surfaces was characterised by its centre of area moving outwards and away from the osteotomy, on both proximal and distal fragments. Subsequent weeks showed consolidation and resorption from the outer surface of the callus.Our approach allowed bony callus development to be tracked in individuals throughout healing. Contrary to the view that periosteal bone formation originates distant from the fracture, our data showed bony callus adjacent to the defect from early stages, followed by approximately concentric growth. This discrepancy highlights the need for data specific to experimental conditions, and particularly early stages of healing, for evaluating theoretical models of mechanical regulation

Biphasic plating improves the mechanical performance of locked plating for distal femur fractures

Internal fixation by plate osteosynthesis is the gold standard treatment for distal femur fractures. Despite improvements that preserve the biological conditions for bone healing, there are concerns standard locked plating constructs may be overly stiff. Biphasic plating is a novel concept designed to provide suitable fracture motion and increased implant strength to support early full weight-bearing. This study aims to demonstrate that the Biphasic Plate can be incorporated into a pre-contoured distal femur plate while providing adequate flexibility and increased implant strength. The mechanical performance of the Biphasic Plate (BP) was investigated in comparison to a standard locking plate for the distal femur (LCP-DF). Constructs were formed by mounting the implants on a bone substitute. The construct stiffness and strength under axial loading and the magnitude of interfragmentary movement were determined using finite element analysis. The Biphasic Plate exhibited a bi-linear stiffness response; at low loads, the BP construct was 55% more compliant and at high loads 476% stiffer than the LCP-DF. The Biphasic Plate provided more consistent interfragmentary movement over a wider loading range. At partial weight-bearing loads, the Biphasic Plate produced larger interfragmentary movements (0.18 vs. 0.04 mm). However, at loads equivalent to full weight-bearing, the maximum movements were substantially smaller than the LCP-DF construct (1.5 vs. 3.5 mm). The increased flexibility at low loads was provided without sacrificing implant strength with peak stress in the Biphasic Plate 63% lower than the LCP-DF construct. The biphasic plating concept can be successfully incorporated into anatomically contoured distal femur plates while providing adequate flexibility and increasing implant strength.</p

Programable active fixator system for systematic in vivo investigation of bone healing processes

This manuscript introduces a programable active bone fixator system that enables systematic investigation of bone healing processes in a sheep animal model. In contrast to previous systems, this solution combines the ability to precisely control the mechanical conditions acting within a fracture with continuous monitoring of the healing progression and autonomous operation of the system throughout the experiment. The active fixator system was implemented on a double osteotomy model that shields the experimental fracture from the influence of the animal’s functional loading. A force sensor was integrated into the fixator to continuously measure stiffness of the repair tissue as an indicator for healing progression. A dedicated control unit was developed that allows programing of different loading protocols which are later executed autonomously by the active fixator. To verify the feasibility of the system, it was implanted in two sheep with different loading protocols, mimicking immediate and delayed weight‐bearing, respectively. The implanted devices operated according to the programmed protocols and delivered seamless data over the whole course of the experiment. The in vivo trial confirmed the feasibility of the system. Hence, it can be applied in further preclinical studies to better understand the influence of mechanical conditions on fracture healing.</p

The absence of immediate stimulation delays bone healing

Aim: Secondary bone healing requires an adequate level of mechanical stimulation expressed by the extent of interfragmentary motion in the fracture. However, there is no consensus about when the mechanical stimulation should be initiated to ensure a timely healing response. Therefore, this study aims to compare the effect of the immediate and delayed application of mechanical stimulation in a large animal model. Methods: Twelve Swiss White Alpine sheep underwent partial osteotomy of a tibia that was stabilised with an active fixator inducing well-controlled mechanical stimulation. Animals were randomly assigned into two groups with different stimulation protocols. The immediate group received daily stimulation (1000 cycles/day) from the first day post-operation, while in the delayed group, stimulation began only on the 22nd day post-operation. Healing progression was evaluated daily by measuring the in vivo stiffness of the repair tissue and by quantifying callus area on weekly radiographs. All animals were euthanised five weeks post-op. Post-mortem callus volume was determined from high-resolution computer tomography (HRCT). Results: Fracture stiffness (p < 0.05) and callus area (p < 0.01) were significantly larger for the immediate group compared to the delayed stimulation group. In addition, the callus volume measured on the post-mortem HRCT showed 319 % greater callus volume for the immediate stimulation group (p < 0.01). Conclusions: This study demonstrates that a delay in the onset of mechanical stimulation retards fracture callus development and that mechanical stimulation already applied in the early post-op phase promotes bone healing.</p

Severity of Complications after Locking Plate Osteosynthesis in Distal Femur Fractures

Background: Locked plating for distal femur fractures is widely recommended and used. We systematically reviewed clinical studies assessing the benefits and harms of fracture fixation with locked plates in AO/OTA Type 32 and 33 femur fractures. Methods: A comprehensive literature search of PubMed, Embase, Cinahl, Web of Science, and the Cochrane Database was performed. The studies included randomized and non-randomized clinical trials, observational studies, and case series involving patients with distal femur fractures. Studies of other fracture patterns, studies conducted on children, pathological fractures, cadaveric studies, animal models, and those with non-clinical study designs were excluded. Results: 53 studies with 1788 patients were found to satisfy the inclusion and exclusion criteria. The most common harms were nonunion (14.8%), malunion (13%), fixation failure (5.3%), infection (3.7%), and symptomatic implant (3.1%). Time to full weight-bearing ranged from 5 to 24 weeks, averaging 12.3 weeks. The average duration of follow-up was 18.18 months, ranging from 0.5 to 108 months. Surgical time ranged between 40 and 540 min, with an average of 141 min. The length of stay in days was 12.7, ranging from 1 to 61. The average plate length was ten holes, ranging from 5 to 20 holes. Conclusion: This review aimed to systematically synthesize the available evidence on the risk associated with locked plating osteosynthesis in distal femur fractures. Nonunion is the most common harm and is the primary cause of reoperation. The overall combined risk of a major and critical complication (i.e., requiring reoperation) is approximately 20%