C⁴Bio

After having received applications from all over the world, the selected participants for the first test campaign on uniaxial tensile testing of porcine aorta are shown below.

Context

Computational modeling is successfully used to address safety-critical issues and to provide evidence in the regulatory approval process in the aerospace, automotive, and nuclear industries for quite some time. The healthcare industry is also moving towards this in silico approach, which can be used in all phases of R&D, from the design of the product, over development to the regulatory approval and post-marketing stage. Besides a clear definition of the context of use and a rigorous verification and validation process (as provided by ASME V&V40), the quality of the model input has a great influence on the model credibility. Therefore, the accurate representation of the involved biological tissues is identified as a significant barrier for in silico medicine to truly impact the healthcare industry and become an accepted method for evidence generation in the regulatory approval process.

Problem statement

Although the scientific literature abounds with articles experimentally characterizing biological tissues, the reported parameters often show a high variability, partially due to the absence of widely recognized testing standards for biological tissue.

The aim of the challenge is to achieve community consensus regarding the testing protocols for material characterization of biological tissue and disseminate this consensus to the relevant standards bodies (i.a. ISO & ASME). The physical properties of interest can be thermal, mechanical or electrophysiological. In the first stage, this challenge will focus on mechanical tissue properties collected through in vitro experiments.

In vitro mechanical characterization of biological material entails many aspects, including tissue collection, preservation, preparation, experimental set-up, protocol development, execution and post processing. A wide variety of testing methods exist which are often specific to the tissue, the material parameters of interest and the clinical situation of interest. Standardization in this broad field is non-trivial. The challenge will therefore be organized in different test campaigns, each time focusing on a single aspect.

Four phases

For each test campaign the following four phases (click for more information) are identified:

• Variability quantification (test round 1)
  Quantify the variability of material mechanical properties resulting from 'identical' experiments performed by different research groups. The participants are requested to apply their own methodology to perform the experiments on a sample set provided by C⁴Bio, and send back a description of their methodology along with the obtained results. During a colloquium to be attended by all participants, C⁴Bio will bundle all received data and report on the variation in the applied methodology as well as the variability of the test results.
• Consensus definition (colloquium)
  During the same colloquium, all participants will engage in a discussion to reach a consensus methodology covering each aspect of the test, with the aim of maximizing practicality, accuracy, reproducibility and acceptability. Apart from the participating teams, experts from standards-related organizations will join the discussion.
• Consensus evaluation (test round 2)
  Evaluate the benefit of the consensus methodology. Participants will then repeat the experiment based on the consensus methodology during a second testing campaign. The reduction in interlaboratory variability as compared to the first testing round will be quantified. The outcome will again be discussed among all participants for small improvements on the first version of the consensus methodology as well as on guidelines for reporting.
• Dissemination
  Make the outcome publicly available. The final consensus methodology will be published as guidelines for experimentalists through a white paper, which the participants will be invited to co-author. Secondly, the data collected in the second round of experiments will be made publicly available in a centralized database.

This procedure will be performed for common testing methods (uniaxial tensile testing, planar biaxial tensile testing, extension-inflation testing, unconfined and confined compression testing, etc.) and for relevant tissue types, each time reaching a new consensus methodology as well as expanding the database.

Current test campaign

The first test campaign has started in January 2021 and is focusing on uniaxial tensile testing of soft biological tissue (in casu porcine aorta) to obtain linearized stiffness moduli and ultimate stress and strain values.

The tensile test is a fundamental test in engineering, largely documented and already standardized for metals, composites and plastics. This kind of loading and its outcome parameters can be considered as one of the most common, simple and useful in the biomechanical engineering field, making it the ideal place to start.

Currently, the campaign is in the tensile test is iterating between the consensus definition and consensus evaluation. A list of contributing authors can be found here .

Upcoming test campaigns

The second test campaign will tackle planar biaxial tensile testing, which is another very commonly used method for tissue characterization that has various sources of variability. The tentative registration deadline of this campaign will be April 1st 2022.

Suggestions?

Do you have suggestions for an upcoming test campaign? Contact us

We invite all research groups with experience in material characterization of biological tissue to join this initiative. The prerequisites are:

• The availability of infrastructure suitable for current test campaign.
• The clearance to test biological tissue in your lab.
• A demonstrated experience in mechanical experiments on biological tissue through scientific references.
• The willingness to publicly share the experimental results (i.e. in the resulting white paper and database).

For practical reasons, the number of participating groups is limited to 20. A selection will be made based on:

• Expertise and track record on testing of biological tissue.
• Potential for the group to join in the following campaigns (i.e. expertise in and facilities for more than one test method).
• Geographical spread.

Participants taking part in a test campaign will:

• be part of a unique consortium consisting of academic and industry experts at the forefront of standardization in material characterization of biological tissue.
• drive forward the field of in silico medicine by contributing to a key breakthrough in one of the most significant barriers to ubiquitous adoption of computational biological models.
• be involved as co-authors in the resulting white paper.