Coupled analysis of active biological processes for meniscus tissue regeneration -Experiments, statistical data processing, and data-informed in-silico modeling

Coupled analysis of active biological processes for meniscus tissue regeneration - Experiments, statistical data processing, and data-informed in-silico modeling

PIs: Bernd Simeon, Christina Surulescu, Claudia Redenbach, Andreas Seitz

Aim:

The project deals with the modeling, simulation and experimental validation of meniscus tissue regeneration and the involved phenomena on cell and tissue level, based on a non-woven scaffold that is colonized by stem cells.

Description:

Meniscal lesions are among the most common injuries of the knee joint. While tears in the vascularized, outer region of the meniscus can be treated by different suture techniques with good clinical outcomes, tears in the inner, avascular zone have only limited regeneration potential and result in partial or even total meniscectomy and a high risk of chondral damage that finally might end up in premature osteoarthritis. There is, thus, a strong need for an alternative treatment. Although artificial tissues such as polyurethane or allogenic collagen implants have been introduced in recent years as replacement materials, an adequate and durable meniscal replacement is still missing. Our overall goal is thus the development of a regenerative approach where an artificial scaffold is seeded with mesenchymal stem cells that differentiate into chondrocytes and build up a stable collagen structure. Patient-specific data of real menisci serve as target parameters for our interdisciplinary investigations. While we have made great strides towards this goal in the still running first project phase, there are several challenging issues ahead that can only be addressed in a long-term study and a corresponding second project phase. More specifically, the proposed second project phase will advance the present mathematical models, mainly diffusion-reaction-advection equations with mechanical coupling terms, their numerical simulation, and the experimental cell culturing framework to a new level. There, improvements of the in-vitro experiment can be identified and derived from exploration of the in-silico model , and the experiments as well as quantitative image analysis enable in turn a more detailed and data-informed mathematical description. Control variables in this regard are not only the biological and chemical processes, but also characteristic properties of the scaffold geometry. By expanding the experimental studies and the computational model to patient-specific meniscus tissues, we propose to create a hypothetical ex-vivo framework that can provide insight into the relevant processes after an implantation with artificial replacement tissues. Our proposal combines mathematical modeling on multiple scales for a new problem class, numerical simulation in space and time with emphasis on model order reduction and parameter identification, and advanced in-vitro experiments with artificial scaffolds and native meniscus tissues. Additional expertise from quantitative image analysis strengthens our interdisciplinary approach, yielding important new data and also carrying the potential for scaffold design. Summarizing, the major outcome of this project will set up the rationale for the future design of regenerative meniscus replacement material.

Involved Institutions:

RPTU Kaiserslautern-Landau, Dept. of Mathematics
Universität Ulm, Institute of Orthopaedic Research and Biomechanics

Links:

https://math.rptu.de

https://www.uni-ulm.de/en/med/institute-of-orthopaedic-research-and-biomechanics/

Applicants:

Bernd Simeon

RPTU Kaiserslautern-Landau, Dept. of Mathematics

Christina Surulescu

RPTU Kaiserslautern-Landau, Dept. of Mathematics

Claudia Redenbach

RPTU Kaiserslautern-Landau, Dept. of Mathematics

Andreas Seitz

Universität Ulm, Institute of Orthopaedic Research and Biomechanics

Henry Jäger

RPTU Kaiserslautern-Landau, Dept. of Mathematics

Publications

2025

Nogatz, T.; Redenbach, C.; Schladitz, K.

MorphFlow: Estimating Motion in In-Situ Tests of Concrete Artikel

In: Exp Mech, Bd. 65, Nr. 1, S. 35–53, 2025, ISSN: 1741-2765.

Abstract | Links | BibTeX

@article{Nogatz2024,

title = {MorphFlow: Estimating Motion in In-Situ Tests of Concrete},

author = {T. Nogatz and C. Redenbach and K. Schladitz},

doi = {10.1007/s11340-024-01104-7},

issn = {1741-2765},

year  = {2025},

date = {2025-01-00},

urldate = {2025-01-00},

journal = {Exp Mech},

volume = {65},

number = {1},

pages = {35--53},

publisher = {Springer Science and Business Media LLC},

abstract = {<jats:title>Abstract</jats:title>

          <jats:sec>

            <jats:title>Background</jats:title>

            <jats:p>

              <jats:italic>In situ</jats:italic> Computed Tomography is a valuable tool to investigate failure mechanics of materials in 3D. For brittle materials with sudden fracture like concrete however, state-of-the-art methods such as Digital Volume Correlation fail to produce displacement fields that display the discontinuous behavior of load induced cracking correctly.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Objective</jats:title>

            <jats:p>The main objective is to develop an algorithm that calculates displacement fields for large-scale <jats:italic>in situ</jats:italic> experiments on concrete.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Methods</jats:title>

            <jats:p>The algorithm presented is based on a 3D Optical Flow method solved by a primal-dual procedure and equipped with a coarse-to-fine scheme based on morphological wavelets. The algorithm is publicly available. Our evaluation focuses on the beneficial use of morphological wavelets over classical ones, and on the ability to produce reliable results with limited data. Applying the primal-dual scheme to <jats:italic>in situ</jats:italic> tests and using morphological wavelets are novel contributions.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Results</jats:title>

            <jats:p>The results show that our algorithm cannot only cope with large volume images, but also produces discontinuous displacement fields that yield high strain in fractured regions. It does not only perform better than state-of-the-art methods, but also achieves sufficient results on reduced data. The morphological wavelets play a key role in this finding - they even allow to deduce cracks of widths less than a voxel.</jats:p>

          </jats:sec>

          <jats:sec>

            <jats:title>Conclusion</jats:title>

            <jats:p>Displacement calculation for <jats:italic>in situ</jats:italic> tests of brittle materials requires voxel-accurate displacement fields that allow for discontinuities. The presented algorithm fulfills these requirements and therefore is a powerful tool for future understanding of failure mechanics in concrete.</jats:p>

          </jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Schließen

Abstract

Background

In situ Computed Tomography is a valuable tool to investigate failure mechanics of materials in 3D. For brittle materials with sudden fracture like concrete however, state-of-the-art methods such as Digital Volume Correlation fail to produce displacement fields that display the discontinuous behavior of load induced cracking correctly.

Objective
The main objective is to develop an algorithm that calculates displacement fields for large-scale in situ experiments on concrete.

Methods
The algorithm presented is based on a 3D Optical Flow method solved by a primal-dual procedure and equipped with a coarse-to-fine scheme based on morphological wavelets. The algorithm is publicly available. Our evaluation focuses on the beneficial use of morphological wavelets over classical ones, and on the ability to produce reliable results with limited data. Applying the primal-dual scheme to in situ tests and using morphological wavelets are novel contributions.

Results
The results show that our algorithm cannot only cope with large volume images, but also produces discontinuous displacement fields that yield high strain in fractured regions. It does not only perform better than state-of-the-art methods, but also achieves sufficient results on reduced data. The morphological wavelets play a key role in this finding - they even allow to deduce cracks of widths less than a voxel.

Conclusion
Displacement calculation for in situ tests of brittle materials requires voxel-accurate displacement fields that allow for discontinuities. The presented algorithm fulfills these requirements and therefore is a powerful tool for future understanding of failure mechanics in concrete.

Schließen

2024

Jäger, Henry; Grosjean, Elise; Plunder, Steffen; Redenbach, Claudia; Keilmann, Alex; Simeon, Bernd; Surulescu, Christina

Cell seeding dynamics in a porous scaffold material designed for meniscus tissue regeneration Artikel

In: Proc Appl Math and Mech, Bd. 24, Nr. 2, 2024, ISSN: 1617-7061.

Abstract | Links | BibTeX

Schwer, Jonas; Ignatius, Anita; Seitz, Andreas Martin

The biomechanical properties of human menisci: A systematic review Artikel

In: Acta Biomaterialia, Bd. 175, S. 1–26, 2024, ISSN: 1742-7061.

Links | BibTeX

Grosjean, Elise; Keilmann, Alex; Jäger, Henry; Mohanan, Shimi; Redenbach, Claudia; Simeon, Bernd; Surulescu, Christina; Roy, Luisa; Seitz, Andreas; Teixeira, Graciosa; Dauner, Martin; Linti, Carsten; Schmidt, Günter

An in-silico approach to meniscus tissue regeneration: Modeling, numerical simulation, and experimental analysis Sonstige

2024.

Links | BibTeX