Publications of Liesbet Geris
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See detailComputational modelling of the effect of growth factors on human mesenchymal stem cell proliferation in 3D porous scaffolds
Mehrian, Mohammad ULiege; Papantoniou, Ioannis; Lambrechts, Toon et al

in Proceedings of the Virtual Physiological Human conference (VPH), Zaragoza, Spain, 5-7 September 2018 (2018, September 05)

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See detailThe future is digital: In silico tissue engineering
Geris, Liesbet ULiege; Lambrechts, Toon; Carlier, Aurélie et al

in Current Opinion in Biomedical Engineering (2018), 6

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See detailMulti-objective optimization of cost-efficient neotissue growth inside 3D scaffolds using evolutionary algorithms
Mehrian, Mohammad ULiege; olofsson, Simon; Misener, Ruth et al

in Proceedings of the 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE) (2018, March 26)

Tissue engineering is a fast progressing domain where solutions are provided for organ failure or tissue damage. Computer models can facilitate the design of optimal production process conditions leading ... [more ▼]

Tissue engineering is a fast progressing domain where solutions are provided for organ failure or tissue damage. Computer models can facilitate the design of optimal production process conditions leading to robust and economically viable products. We developed a computational model describing the neotissue growth (cells + their ECM) inside 3D scaffolds in a perfusion bioreactor. Here we apply multi-objective optimization (MOO) to maximize neotissue growth whilst minimizing the cost coming from medium refreshment and associated labor. [less ▲]

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See detailComputational modelling of human mesenchymal stem cell proliferation and extra cellular matrix production in 3D porous scaffolds in a perfusion bioreactor
Mehrian, Mohammad ULiege; Papantoniou, Ioannis; Lambrechts, Toon et al

in Proceedings of the 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE) (2018, March 26)

3D porous scaffolds are frequently used in tissue engineering (TE) applications in combination with bioreactor systems because of their ability to induce reproducible culture conditions that can control ... [more ▼]

3D porous scaffolds are frequently used in tissue engineering (TE) applications in combination with bioreactor systems because of their ability to induce reproducible culture conditions that can control specific cell behavior such as proliferation and extracellular matrix (ECM) production. A computational model describing neotissue growth inside 3D scaffolds in a perfusion bioreactor was developed, with neotissue being considered the combination of cells and their extra cellular matrix. In the model, the speed of neotissue growth depends on the flow-induced shear stress, curvature and the local concentrations of oxygen, glucose and lactate. The goal of this study is to make a distinction between the cell and the ECM fraction within the neotissue in the model to allow for a more detailed validation and optimization of the process. [less ▲]

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See detailComputational Bone Tissue Engineering: Virtual Models for Living Implants
Geris, Liesbet ULiege

Conference (2018)

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See detailComputational modeling of tissue regeneration
Geris, Liesbet ULiege

Scientific conference (2018)

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See detailMultiphysics modeling for skeletal tissue engineering
Geris, Liesbet ULiege

Conference (2018)

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See detailIn silico clinical trials for pediatric orphan diseases.
Carlier, Aurélie; Vasilevich, A.; de Boer, J. et al

in Scientific Reports (2018), 8(1), 2465

To date poor treatment options are available for patients with congenital pseudarthrosis of the tibia (CPT), a pediatric orphan disease. In this study we have performed an in silico clinical trial on 200 ... [more ▼]

To date poor treatment options are available for patients with congenital pseudarthrosis of the tibia (CPT), a pediatric orphan disease. In this study we have performed an in silico clinical trial on 200 virtual subjects, generated from a previously established model of murine bone regeneration, to tackle the challenges associated with the small, pediatric patient population. Each virtual subject was simulated to receive no treatment and bone morphogenetic protein (BMP) treatment. We have shown that the degree of severity of CPT is significantly reduced with BMP treatment, although the effect is highly subject-specific. Using machine learning techniques we were also able to stratify the virtual subject population in adverse responders, non-responders, responders and asymptomatic. In summary, this study shows the potential of in silico medicine technologies as well as their implications for other orphan diseases. [less ▲]

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See detailVirtual physiological human 2016: Translating the virtual physiological human to the clinic
Hoekstra, A. G.; Bavel, E. V.; Siebes, M. et al

in Interface Focus (2018), 8(1),

[No abstract available]

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See detailAdvancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo.
Mendes, L. F.; Katagiri, H.; Tam, W. L. et al

in Stem Cell Research and Therapy (2018), 9(1), 42

BACKGROUND: Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue ... [more ▼]

BACKGROUND: Chondrogenic mesenchymal stem cells (MSCs) have not yet been used to address the clinical demands of large osteochondral joint surface defects. In this study, self-assembling tissue intermediates (TIs) derived from human periosteum-derived stem/progenitor cells (hPDCs) were generated and validated for stable cartilage formation in vivo using two different animal models. METHODS: hPDCs were aggregated and cultured in the presence of a novel growth factor (GF) cocktail comprising of transforming growth factor (TGF)-beta1, bone morphogenetic protein (BMP)2, growth differentiation factor (GDF)5, BMP6, and fibroblast growth factor (FGF)2. Quantitative polymerase chain reaction (PCR) and immunohistochemistry were used to study in vitro differentiation. Aggregates were then implanted ectopically in nude mice and orthotopically in critical-size osteochondral defects in nude rats and evaluated by microcomputed tomography (microCT) and immunohistochemistry. RESULTS: Gene expression analysis after 28 days of in vitro culture revealed the expression of early and late chondrogenic markers and a significant upregulation of NOGGIN as compared to human articular chondrocytes (hACs). Histological examination revealed a bilayered structure comprising of chondrocytes at different stages of maturity. Ectopically, TIs generated both bone and mineralized cartilage at 8 weeks after implantation. Osteochondral defects treated with TIs displayed glycosaminoglycan (GAG) production, type-II collagen, and lubricin expression. Immunostaining for human nuclei protein suggested that hPDCs contributed to both subchondral bone and articular cartilage repair. CONCLUSION: Our data indicate that in vitro derived osteochondral-like tissues can be generated from hPDCs, which are capable of producing bone and cartilage ectopically and behave orthotopically as osteochondral units. [less ▲]

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See detailIn silico methods - Computational alternatives to animal testing.
Lang, Annemarie; Volkamer, Andrea; Behm, Laura et al

in ALTEX (2018), 35(1), 124-126

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See detailSimultaneous three-dimensional visualization of mineralized and soft skeletal tissues by a novel microCT contrast agent with polyoxometalate structure.
Kerckhofs, Greet; Stegen, Steve; van Gastel, Nick et al

in Biomaterials (2018), 159

Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced ... [more ▼]

Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced microfocus computed tomography (CE-CT), a Hafnium-based Wells-Dawson polyoxometalate (Hf-POM), which allows simultaneous 3D visualization of mineralized and non-mineralized skeletal tissues, such as mineralized bone and bone marrow vasculature and adipocytes. We validated the novel contrast agent, which has a neutral pH in solution, by detailed comparison with (immuno)histology on murine long bones as blueprint, and showed that Hf-POM-based CE-CT can be used for virtual 3D histology. Furthermore, we quantified the 3D structure of the different skeletal tissues, as well as their spatial relation to each other, during aging and diet-induced obesity. We discovered, based on a single CE-CT dataset per sample, clear differences between the groups in bone structure, vascular network organization, characteristics of the adipose tissue and proximity of the different tissues to each other. These findings highlight the complementarity and added value of Hf-POM-based CE-CT compared to standard histomorphometry. As this novel technology provides a detailed 3D simultaneous representation of the structural organization of mineralized bone and bone marrow vasculature and adipose tissue, it will enable to improve insight in the interactions between these three tissues in several bone pathologies and to evaluate the in vivo performance of biomaterials for skeletal regeneration. [less ▲]

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See detailMaximizing neotissue growth kinetics in a perfusion bioreactor: An in silico strategy using model reduction and Bayesian optimization
Mehrian, Mohammad ULiege; Guyot, Y.; Papantoniou, I. et al

in Biotechnology and Bioengineering (2017)

In regenerative medicine, computer models describing bioreactor processes can assist in designing optimal process conditions leading to robust and economically viable products. In this study, we started ... [more ▼]

In regenerative medicine, computer models describing bioreactor processes can assist in designing optimal process conditions leading to robust and economically viable products. In this study, we started from a (3D) mechanistic model describing the growth of neotissue, comprised of cells, and extracellular matrix, in a perfusion bioreactor set-up influenced by the scaffold geometry, flow-induced shear stress, and a number of metabolic factors. Subsequently, we applied model reduction by reformulating the problem from a set of partial differential equations into a set of ordinary differential equations. Comparing the reduced model results to the mechanistic model results and to dedicated experimental results assesses the reduction step quality. The obtained homogenized model is 105 fold faster than the 3D version, allowing the application of rigorous optimization techniques. Bayesian optimization was applied to find the medium refreshment regime in terms of frequency and percentage of medium replaced that would maximize neotissue growth kinetics during 21 days of culture. The simulation results indicated that maximum neotissue growth will occur for a high frequency and medium replacement percentage, a finding that is corroborated by reports in the literature. This study demonstrates an in silico strategy for bioprocess optimization paying particular attention to the reduction of the associated computational cost. © 2017 Wiley Periodicals, Inc. [less ▲]

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See detailBayesian Multi-Objective Optimisation of Neotissue Growth in a Perfusion Bioreactor Set-up
olofsson, Simon; Mehrian, Mohammad ULiege; Geris, Liesbet ULiege et al

in Computer Aided Chemical Engineering (2017, October 01)

We consider optimising bone neotissue growth in a 3D scaffold during dynamic perfusion bioreactor culture. The goal is to choose design variables by optimising two conflicting objectives: (i) maximising ... [more ▼]

We consider optimising bone neotissue growth in a 3D scaffold during dynamic perfusion bioreactor culture. The goal is to choose design variables by optimising two conflicting objectives: (i) maximising neotissue growth and (ii) minimising operating cost. Our contribution is a novel extension of Bayesian multi-objective optimisation to the case of one black-box (neotissue growth) and one analytical (operating cost) objective function, that helps determine, within a reasonable amount of time, what design variables best manage the trade-off between neotissue growth and operating cost. Our method is tested against and outperforms the most common approach in literature, genetic algorithms, and shows its important real-world applicability to problems that combine black-box models with easy-to-quantify objectives like cost. [less ▲]

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See detailModelling BMP-2 carrier device for bone tissue engineering application
Manhas, Varun ULiege; Carlier, Aurelie; Geris, Liesbet ULiege

Poster (2017, February 01)

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See detailMAXIMIZING NEOTISSUE GROWTH IN A PERFUSION BIOREACTOR USING BAYESIAN OPTIMIZATION
Mehrian, Mohammad ULiege; guyot, Yann; Papantoniou, Ioannis et al

Poster (2017, February 01)

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See detailModel-Based Optimization of the Medium Refreshment Regime During Neotissue Growth in a Perfusion Bioreactor
Mehrian, Mohammad ULiege; guyot, Yann; Papantoniou, Ioannis et al

in Proceedings of the Foundations of Computer Aided Process Operations / Chemical Process Control (FOCAPO/CPC) (2017, January 08)

Computational models are interesting tools to facilitate the translation from the laboratory to the patient. In regenerative medicine, computer models describing bioprocesses taking place in bioreactor ... [more ▼]

Computational models are interesting tools to facilitate the translation from the laboratory to the patient. In regenerative medicine, computer models describing bioprocesses taking place in bioreactor environment can assist in designing process conditions leading to robust and economically viable products. In this study we present a low-cost computational model describing the neotissue (cells + extracellular matrix) growth in a perfusion bioreactor set-up. The neotissue growth is influenced by the geometry of the scaffold, the flow-induced shear stress and a number of metabolic factors. After initial model validation, a Genetic Algorithm optimization technique is used to find the best medium refreshment regime (frequency and percentage of medium replaced) resulting in a maximal amount of neotissue being produced in the scaffold in a 28 days of culture period. [less ▲]

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See detailMathematical modeling in regenerative medicine: from bench to bedside
Geris, Liesbet ULiege

Conference (2017)

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