草榴社区

Simpleware Case Study: In Silico Trial Investigating the Safety of a New Personalized 3D Printed High Tibial Osteotomy Device

Personalized 3D printed high tibial osteotomy (HTO)

Overview

One way to treat early knee osteoarthritis is through a high tibial osteotomy (HTO). However, HTO is challenging and may cause complications. In this study, a new personalized HTO device has been developed using Simpleware software to create virtual models from 28 real patients.

The evidence from this study was particularly notable for being the first computer-modelled trial in the world to demonstrate the safety of an orthopaedic device compared to standard treatment.

The results showed that the personalized device was as safe as the standard device, and was used to gain MHRA approval in the UK for ongoing clinical trials to increase the use of HTO as a treatment option.

Highlights

  • Novel in silico trial used to compare mechanical safety of a personalized 3D printed high tibial osteotomy (HTO) device to an existing generic device
  • Simpleware software used to generate 28 simulation-ready models from patient CT data, as well as scans of the generic device
  • Results show no increased risk to the safety of the new device, supporting the case for personalized HTO

Reference

MacLeod, A.R., et al., 2021. . Communications Medicine, 1(6).

Thanks to

University of Bath; University of Oxford; Polytechnic University of Catalonia; Royal Devon & Exeter NHS Trust; Rice University

"Simpleware software was instrumental in creating the finite element models used for this study, performing the segmentation, meshing and assignment of material properties based on bone density."

Prof Richie Gill, University of Bath

Introduction

High tibial osteotomy (HTO) is a simple and effective treatment for early knee osteoarthritis. Younger patients may prefer HTO over total knee replacements which are more common for older people as they have less demand for long-lasting performance. However, few surgeons consider this procedure due to the difficulty of achieving accurate planned corrections. In this case study, a novel in silico clinical trial compares the mechanical safety of a new, personalized 3D printed HTO plate with an existing generic model to better evaluate its safety and effectiveness.

HTO involves creating an opening or closing wedge osteotomy in the proximal tibial to change the varus alignment, therefore altering the mechanical axis of the leg, and reducing the load in the painful compartment. Osteotomy is commonly stabilized using an osteosynthesis plate, with common complications including pain and discomfort from soft-tissue irritation. Achieving sufficient plate flexibility is therefore crucial for long-term bone healing and positive patient outcomes. As patient-specific plates are optimized to individual bone geometries, this may improve their fit and reduce complications. In addition, digital 3D planning with personalized tibial geometries allows pre-operative determination of screw lengths and orientations that can help reduce operative time.

In silico clinical trials enable simulation of multiple surgeries on virtual copies of the same individual to compare on a paired basis the mechanical outcomes and risk of failure between new and established interventions, whereby each participant is their own control. These trials follow the same conventions and control protocols as physical clinical trials. This study particularly focused on the peak mechanical stress in the implanted plates during physiological loading, as determined by finite element analysis (FEA). No increased risk of failure was identified for the new personalized device compared to the existing generic device, increasing confidence in the use of HTO.

Data Preparation and Image Processing

30 knee osteoarthritis patients underwent CT scanning, with 2 patients disqualified due to poor CT scanning results, leaving a cohort of 28 anonymized datasets. A power analysis was performed for standard sized TomoFix HTO plates (DePuy Synthes) using experimentally measured variation in stiffness and strength. This input helped determine the suitability of the patient cohort size. The TomoFix HTO plate is a widely implanted HTO device and was used as the ‘generic device’ in this study.

The CT data was imported into Simpleware software for segmentation, and five key landmarks of interest were identified. The required osteotomy correction angle was calculated using MATLAB so that the altered mechanical axis passed through a point 62.5% of the distance from the medial to the lateral tibial plateau. Virtual HTO surgery was performed on each patient to alter the mechanical axis of the knee by creating an opening wedge osteotomy, Ansys SpaceClaim was used for this procedure, with guidance from an orthopedic surgeon specializing in knee surgery.

3D HTO geometries created using 草榴社区 Simpleware software for designing a surgical guide in Ansys SpaceClaim

Example 3D geometries created using 草榴社区 Simpleware software for designing a surgical guide in Ansys SpaceClaim software.

(a) The planning software generates the geometries of both the HTO stabilization plate, and the surgical guide contoured to the patient’s individual tibia surface geometry; (b) the planning software also records all screw lengths required. ( by Zaffagnini et al. /  / Resized from original).

After the virtual surgeries were performed, each virtual patient was duplicated. One copy had the osteotomy stabilized using the generic plate, and the other using the personalized plate (TOKA, Orthoscape), thus forming the two groups of the trial. For the generic group, the TomoFix high tibial plate was micro-CT scanned (Nikon Metrology) and processed in Simpleware software. For the personalized group, patient-specific implant geometries were created using specialized planning software (Renishaw plc), taking into account the surface of the tibia and the degree of correction for each patient. All simulated knees were virtually implanted with both implant types, therefore generating a total of 56 intervention cases as FE models for simulation in Ansys software.

FE Simulation

The FE models were created, and simulation carried out based on a validated methodology and model, including the method for representing the screw and plate, as well as contact interactions between the components. Patient-specific material properties were applied from each patient’s CT data, using heterogeneous linear elastic properties. Other factors, such as normal contact stiffness, were determined based on experimental testing and Ansys default contact settings. The progression of bone healing was represented by increasing the Young’s modulus of the osteotomy region, with data from previous studies used to quantify the extent of osteotomy gap healing at different time points.

Meshing parameters were based on a previous validated study, and checks made to ensure suitability for the simulation. Muscle forces and joint reaction forces for normal physiological activities were also calculated using a subject-specific musculoskeletal model, with forces automatically registered to the individual patient geometries using a custom transformation and scaling script in MATLAB. Three common activities were considered: fast walking gait, chair rise, and squat, and five key instances selected for each activity based on locations of peak tibial contact force, implemented as load steps 1 to 15 in the FE models.

Simulations were run for both patient models for the physiological activities, three screw configurations, and osteotomy gap bone healing stages at different time intervals: healing stage 1 covered the immediate post-operative period (not simulated but included in the ClinicalTrials.gov entry, and included for consistency), healing stage 2 was 2-weeks after surgery, healing stage 3 was 6 weeks after surgery, and healing stage 4 was 12 weeks after surgery.

The principal outcome variable was the maximum Von Mises stress within the plates, within the bone adjacent to the screws used to fix the plates, and within the inter-fragmentary movement at the osteotomy site. Fatigue failure was taken into account as a variable for all metal implants, based on fatigue testing. Statistical analysis of the effect of the three screw configurations was also conducted.

Maximum Von Mises Stress (MPa) in each type of HTO plate

Maximum Von Mises Stress (MPa) in each type of HTO plate at healing stage 2 (HS2) for each load step for screw configurations 1, 2 and 3.

The circles are the maximum Von Mises Stress for each virtual subject implanted with the Generic plate, and the plus symbols are for the Personalized plate, at each loading step (n=28 independent models for each arm, Generic and Personalized) ( by MacLeod et al. /  / Resized from original).

Results

Solving of the FE models was computationally intense, requiring 500,477 core hours on a high-performance computing cluster. The results indicated that the effects of screw configuration on the Von Mises stress in each type of plate were not statistically significant, with a large degree of overlap between the confidence intervals, while the effect of the healing stage was very dramatic in reducing the maximum Von Mises stresses in both sets of plates. In addition, differences in bone strain around the screw insertions for the two plates were small and not significant. However, the differences in inter-fragmentary movement between the two devices was more significant at healing stage 4 (12 weeks post-operatively) due to increased micro-motion in the personalized device.

As the main failure mechanism for these devices is fatigue failure, the key result was the odds ratio indicative of the relative risk of failure between the personalized and generic groups at different healing stages. While the personalized HTO plates consistently had larger stress values than their generic counterparts, the delta values were relatively small. More importantly, the personalized HTO plates had no difference in their risk of failure compared to generic plates, whilst being more mechanically efficient and less stiff. These results demonstrated that 3D printed, patient-specific plates can address critical challenges such as accuracy, stiffness, and geometric conformity, which limit the current use of HTO surgery, while also enabling simpler and quicker surgeries.

Conclusions

The breakthrough use of in silico trials for orthopaedic safety testing and informing clinical trials showed no increased risk of failure for the personalized design versus the generic design.

The results support further clinical studies looking at the benefits of patient-specific over standard realignment surgery, and the potential of this method for treating early knee arthritis. Future in silico trials could broaden the scope of the study beyond mechanical safety and stability, for example in terms of relative efficacy.

This study formed part of regulatory evidence accepted by MHRA in approval for a subsequent clinical patient trial (the PASHiOn clinical trial). The safety phase in 5 patients using 3D printed HTO plates led to positive outcomes, with one patient being able to participate in a competitive bike ride within 6 months. The intervention involved X-ray and CT scans of patient shin bones (tibia) being used to digitally plan HTO surgery, from which a patient-specific 3D printed surgical guide and stabilization plate were generated. The surgical guide enabled the surgeon to make the cuts and create the appropriate opening wedge which is then stabilized by the plate.

A 25-patient single-group trial at the Rizzoli Institute in Bologna was also conducted and demonstrated successful treatment of patients with the device. The personalized HTO system demonstrated accurate correction in terms of both coronal and sagittal alignment, with excellent patient reported outcomes at a one-year follow-up. An ongoing randomized control trial in the UK () will now compare the novel personalized method with a traditional method.

Professor Richie Gill from the University of Bath commented on the innovative aspect of the research and the contribution of in silico trials to ongoing testing with a larger patient cohort:

"The big difference is there isn't that guesswork which is happening at the time of surgery. I think more surgeons are interested in doing this type of joint-preserving surgery. You can do it at a sooner point in the disease progression than you can with a knee replacement, so we are hoping to make it more widely available."

Learn More

  • Read the full on this study
  • See how personalized HTO is already
  • Read papers from the Rizzoli Orthopaedic Institute in Bologna on the first clinical trial with 25 patients: 
  • Except where otherwise noted, content on this page is licensed under a .

Any Questions?

Do you have any questions about this case study or how to use Simpleware software for your own workflows?