A virtual patient.  That’s what we’re looking for to reduce costs and accelerate the innovation of medical devices and treatments, including those using 3D printing.  And it is these virtual patients that can be a crucial component in helping entrepreneurs and researchers bolster their products for clinical trials. We sat down with five experts who are making computer, or in silico, simulations a reality to benefit patients worldwide.  Here’s a recap of the progress they’ve made and the challenges to come from our 3DHEALS event.

The conventional pathway for developing a medical device can be fraught with expense if problems are found too late in the process.  In silico simulations provide an avenue for researchers and companies to discover effective solutions faster and detect issues earlier.

Already, the United States Food and Drug Administration (FDA) has recognized the increasing utility of computational modeling and recently established guidance on assessing the credibility of in silico evidence for medical device submissions.

Virtual Patients, Not Too Far Away

Simon Sonntag, CEO and Co-Founder of Virtonomy, is streamlining the use of these types of computer simulations using virtual patient cohorts, or simulated versions of patients that mimic a variety of anatomical conditions with the goal of maximal population coverage.  This could be a potentially cost-effective way to test 3D-printed devices before clinical trials and provide evidence for the trials themselves.

Sonntag described how testing a device for transcatheter applications, such as replacing a heart valve, can be challenging due to the variability in vessel tortuosity and diameters between patients.  Virtonomy’s database of computed tomography scans enables them to model a diverse range of vascular geometries for the transfemoral, inferior vena cava, subclavian/jugular vein, and transseptal via the fossa ovalis access routes.

For vessel straightening, the company can simulate the device materials, catheterization process, arterial material, surrounding organs and bones, and calcification. 3D models like these allow users to readily tune anatomical features with their software, testing worse-case scenarios and inclusion-exclusion criteria that can then be used as evidence for regulatory assessments.

Within only a 3-week submission window for a severely ill patient, the company was able to perform in silico fatigue simulations, which provided critical evidence to the German regulatory agency that approved the implantation of the heart valve repair system.

In Silico Simulation Can Help 3D Printed Implants

Companies are also developing software for other parts of the body.  Kelsey Crossman, Business Development Manager for Simq, describes how the company’s software performs biomechanical simulations of maxillary and mandibular patient-specific implants.  Their product, Simq VIT, automates device validation by simulating physiological load conditions and generates FDA-compliant reports as valuable objective evidence of the design process.  The implant can then be 3D printed with greater confidence in point-of-care applications or sent to a manufacturer.

Crossman says their software simulates various chewing conditions, allowing engineers and clinicians to revise their designs based on deformation data before they print.  The company has also developed simulations for virtual patient cohorts and is expanding to thoracic applications.

In Silico Simulation Compliments 3D Printing in Complex Surgical Cases

Also using simulation techniques, Dr. Péter Éltes, Head of the In Silico Biomechanics Laboratory at the National Center for Spinal Disorders in Hungary, recognizes that simply designing custom implants that fit the natural geometry after the surgical removal of structures is not enough.

Dr. Éltes’ recent study uses finite element analysis to determine the stability of lumbopelvic reconstruction after removal of the sacral bone due to a tumor.  Through their in silico analysis, they find that reducing the lumbopelvic distance is needed to increase stability.  Future custom-made 3D-printed implants can now be designed with this added stability technique in mind, showing the potential of computer simulations to inform the engineering of commercial and research 3D-printed medical devices for better clinical outcomes.

Regulatory Landscape Promising but Remains Promising

We have already seen that in silico simulations hold promise in accelerating clinical trials.  Building justification for that potential, Steven Kreuzer, Senior Managing Engineer at Exponent Inc., co-led a team involving the FDA and Dassault Systèmes to retrospectively examine the benefits in silico simulation would have had for an approved mitral transcatheter edge-to-edge repair device to reduce heart valve regurgitation.

Kreuzer describes how they created a tunable virtual patient model for various heart valve anatomies, accounting for differences in thickness, stiffness, and other properties between different valve leaflets.  They then created virtual patient cohorts with a wide distribution of valve properties, looking at the grade reduction in regurgitation among the patients to evaluate the acute device performance.

In Silico Simulation for Pharma Developers, A Different Beast

In silico simulation has applications in drug discovery and development, in addition to medical devices.  Anthony Fejes, CEO and Co-Founder of HTuO Biosciences, is preparing to commercialize the company’s software, which performs physics-based simulations to predict drug behavior. Their software bridges the gap between the high accuracy of quantum mechanics-based simulations and the scalability of molecular modeling software.

In external validation, Fejes showed that the company’s product AtomForge could reduce errors in modeling molecule torsion angles by 82% and out-of-plane errors by 84% for the worst-case scenario, a significant improvement compared to a prior state-of-the-art, the generalized AMBER force field, on the nonsteroidal anti-inflammatory drug mefenamic acid.  The company has also shown lower errors for other drugs that are difficult to simulate compared to OpenFF, another state-of-the-art method.

Perhaps one day, we could combine such drug simulation platforms with 3D bioprinted tissues for in vitro studies of drug candidates, potentially accelerating the process further compared to traditional animal testing.

While in silico simulations have been shown to be a promising avenue for a larger number of use cases, various challenges remain.  For example, Kreuzer notes that work still needs to be done to garner wider acceptance of these technologies for clinical trials.

Sonntag also points out that there could be hurdles if there are differences in the kinds of in silico clinical trial data certain countries will accept, emphasizing the importance of harmonizing regulatory standards internationally.

Additionally, certain artificial intelligence-based simulations may require large amounts of training data, limiting their applicability.

Our speakers show that computational simulations have immense potential to continue growing in their number of use cases, and the 3D printing industry will benefit from the acceleration of the device development and clinical trial process.  To listen in on the full discussion with our speakers, you can watch the recording of our event, and subscribe to join our upcoming events live.

Peter Hsu

Peter Hsu is an editorial intern for 3DHEALS.  He is currently an undergraduate at the University of Illinois Urbana-Champaign and studies bioengineering with a focus on cell and tissue engineering.  He is also minoring in computer science with interests in artificial intelligence and image processing.  Peter conducts research on using computer vision methods to analyze human tissue images and improving the robustness of machine learning workflows.  He is interested in the use of AI to assist tissue engineering and bioprinting research for medical applications.  He is passionate about science communication and leads STEM outreach lessons at schools in the central Illinois area.

Related Links:

Event Recap: Innovation in Melt-Electrowriting (MEW) & 3D Printing

In Silico Simulation for Medtech and Biopharma (Full Recording, On Demand, 2024)

Interview with Zsolt Pásztor: In Silico Simulation and 3D Printing

Interview with Simon Sonntag: CEO, Virtonomy

Virtual Reality Software For Molecular Modeling and Structure-Based Drug Design

3D Printing for Medical Simulation (On Demand)

Design for Medical 3D Printing (On Demand)

Point of Care 3D Printing (On Demand)

Interview with Kelsey Crossman: Simq Simulation