Publications by authors named "Katrien V Bernaerts"

15 Publications

  • Page 1 of 1

Expansion of Ovarian Cancer Stem-like Cells in Poly(ethylene glycol)-Cross-Linked Poly(methyl vinyl ether--maleic acid) and Alginate Double-Network Hydrogels.

ACS Biomater Sci Eng 2020 06 21;6(6):3310-3326. Epub 2020 Apr 21.

State Key Lab of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

A better understanding of cancer stem cells (CSCs) is essential for research on cancer therapy and drug resistance. Currently, increasingly more investigations are focused on obtaining CSCs to study the mechanism of their enhanced malignancy. In this work, three kinds of double-network hydrogels (PEMM/alginate), consisting of poly(ethylene glycol) (PEG) covalently cross-linked poly(methyl vinyl ether--maleic acid) (P(MVE--MA)) (network 1, denoted as PEMM) and Sr (or Ca, Fe) ionically cross-linked alginates (network 2, denoted as SrAlg, CaAlg, or FeAlg), were prepared. The stiffness, morphology, and components of the PEMM/alginate hydrogels were systematically investigated to understand their effects on CSC enrichment. Only the PEMM/FeAlg hydrogels could support the long-term growth, proliferation, and spheroid formation of SK-OV-3 cells. The expression of CSC-related markers was evaluated with the levels of protein and gene at different stages. The cell spheroids cultured in the PEMM/FeAlg hydrogels acquired certain CSC-like properties, thus drug resistance was enhanced, especially in the PEMM-1/FeAlg hydrogel. tumorigenicity experiments also confirmed the presence of more CSCs in the PEMM-1/FeAlg hydrogel. The results suggest that matrix stiffness, morphology, and cations act synergistically on the regulation of the epithelial-mesenchymal transition (EMT), interleukin-6 (IL-6), and Wnt pathways, affecting the invasiveness of ovarian cancer and the conversion of the non-CSCs into CSCs. The PEMM-1/FeAlg hydrogel with lower elastic modulus, a more macroporous morphology, and higher swelling rate can significantly enhance the stemness, malignancy, and tumorigenicity of SK-OV-3 cells.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01967DOI Listing
June 2020

Chitooligosaccharides for wound healing biomaterials engineering.

Mater Sci Eng C Mater Biol Appl 2020 Dec 20;117:111266. Epub 2020 Jul 20.

BioMatter-Biomass Transformation Lab (BTL), École Polytechnique de Bruxelles, Université Libre de Bruxelles, Avenue F.D. Roosevelt, 50 - CP 165/61, 1050 Brussels, Belgium. Electronic address:

Chitooligosaccharides (CHOS) are oligomers of β-(1-4) linked N-acetylglucosamine and D-glucosamine that are produced from chitin or chitosan using different enzymatic or chemical methods. CHOS are water-soluble and non-cytotoxic with diverse bioactivities such as antibacterial, anti-inflammation, anti-obesity, anti-tumor and antioxidant. These biological features make CHOS promising compounds for several medical and food applications. In this review, we critically summarize the biological activities of CHOS in biomaterials engineering with a particular focus on CHOS applications for skin tissue healing and regeneration. We also present an updated overview of CHOS fabrications into wound dressing biomaterials for several in vitro and in vivo studies.
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http://dx.doi.org/10.1016/j.msec.2020.111266DOI Listing
December 2020

Additive Manufacturing Using Melt Extruded Thermoplastics for Tissue Engineering.

Methods Mol Biol 2021 ;2147:75-99

Department of Complex Tissue Regeneration, MERLN Institute for Technology Inspired Regenerative Medicine, Maastricht, The Netherlands.

Melt extrusion of thermoplastic materials is an important technique for fabricating tissue engineering scaffolds by additive manufacturing methods. Scaffold manufacturing is commonly achieved by one of the following extrusion-based techniques: fused deposition modelling (FDM), 3D-fiber deposition (3DF), and bioextrusion. FDM needs the input material to be strictly in the form of a filament, whereas 3DF and bioextrusion can be used to process input material in several forms, such as pellets or powder. This chapter outlines a common workflow for all these methods, going from the material to a scaffold, while highlighting the special requirements of particular methods. A few ways of characterizing the scaffolds are also briefly described.
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http://dx.doi.org/10.1007/978-1-0716-0611-7_7DOI Listing
March 2021

Hydrothermal polymerization towards fully biobased polyazomethines.

Chem Commun (Camb) 2020 Aug 14;56(64):9194-9197. Epub 2020 Jul 14.

Biobased Materials, Faculty of Science and Engineering, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

Microwave assisted polycondensation for the synthesis of (partially) biobased polyazomethines in water (hydrothermal polymerization) was investigated for the first time in this study. The polyazomethines prepared via this environmentally friendly and simple method show comparable characteristics as the polymers prepared via traditional methods in organic solvents.
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http://dx.doi.org/10.1039/d0cc03026kDOI Listing
August 2020

The Forgotten Pyrazines: Exploring the Dakin-West Reaction.

Chemistry 2020 Jun 5;26(36):8090-8100. Epub 2020 Jun 5.

Aachen Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Urmonderbaan 22, 6167 RD, Geleen, The Netherlands.

Pyrazines are an underreported class of N-heterocycles available from nitrogen-rich biomass presenting an interesting functional alternative for current aromatics. In this work, access to pyrazines obtained from amino acids by using the 90 year old Dakin-West reaction was explored. After a qualitative screening several functional proteinogenic amino acids proved good substrates for this reaction, which were successfully scaled to multigram scale synthesis of the corresponding intermediate α-acetamido ketones. Subsequently, the conditions towards pyrazine formation using δ-amino-levulinic acid were optimized, and these were employed to synthesize a relevant set of five functional dimethylpyrazines in high purity. These pyrazines can be considered a versatile toolbox of aromatic building blocks for a wide range of applications, such as in the synthesis of polymers or metal-organic frameworks.
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http://dx.doi.org/10.1002/chem.202000475DOI Listing
June 2020

UV-Curable Biobased Polyacrylates Based on a Multifunctional Monomer Derived from Furfural.

Macromolecules 2020 Feb 7;53(4):1388-1404. Epub 2020 Feb 7.

Aachen-Maastricht Institute for Biobased Materials (AMIBM), Faculty of Science and Engineering, Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands.

The controlled polymerization of a new biobased monomer, 4-oxocyclopent-2-en-1-yl acrylate (4CPA), was established via reversible addition-fragmentation chain transfer (RAFT) (co)polymerization to yield polymers bearing pendent cyclopentenone units. 4CPA contains two reactive functionalities, namely, a vinyl group and an internal double bond, and is an unsymmetrical monomer. Therefore, competition between the internal double bond and the vinyl group eventually leads to gel formation. With RAFT polymerization, when aiming for a degree of polymerization (DP) of 100, maximum 4CPA conversions of the vinyl group between 19.0 and 45.2% were obtained without gel formation or extensive broadening of the dispersity. When the same conditions were applied in the copolymerization of 4CPA with lauryl acrylate (LA), methyl acrylate (MA), and isobornyl acrylate, 4CPA conversions of the vinyl group between 63 and 95% were reached. The additional functionality of 4CPA in copolymers was demonstrated by model studies with 4-oxocyclopent-2-en-1-yl acetate (), which readily dimerized under UV light via [2 + 2] photocyclodimerization. First-principles quantum mechanical simulations supported the experimental observations made in NMR. Based on the calculated energetics and chemical shifts, a mixture of head-to-head and head-to-tail dimers of () were identified. Using the dimerization mechanism, solvent-cast LA and MA copolymers containing 30 mol % 4CPA were cross-linked under UV light to obtain thin films. The cross-linked films were characterized by dynamic scanning calorimetry, dynamic mechanical analysis, IR, and swelling experiments. This is the first case where 4CPA is described as a monomer for functional biobased polymers that can undergo additional UV curing via photodimerization.
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http://dx.doi.org/10.1021/acs.macromol.9b02659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045705PMC
February 2020

Towards High-performance Materials Based on Carbohydrate-Derived Polyamide Blends.

Polymers (Basel) 2019 Mar 4;11(3). Epub 2019 Mar 4.

Faculty of Science and Engineering, Biobased Materials, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

A bio-derived monomer called 2,3:4,5-di--isopropylidene-galactarate acid/ester (GalXMe) has great potential in polymer production. The unique properties of this molecule, such as its rigidity and bulkiness, contribute to the good thermal properties and appealing transparency of the material. The main problem, however, is that like other biobased materials, the polymers derived thereof are very brittle. In this study, we report on the melt blending of GalXMe polyamides (PAs) with different commercial PA grades using extrusion as well as blend characterization. Biobased PA blends showed limited to no miscibility with other polyamides. However, their incorporation resulted in strong materials with high Young moduli. The increase in modulus of the prepared GalXMe blends with commercial PAs ranged from up to 75% for blends with aliphatic polyamide composed of 1,6-diaminohexane and 1,12-dodecanedioic acid PA(6,12) to up to 82% for blends with cycloaliphatic polyamide composed of 4,4'-methylenebis(cyclohexylamine) and 1,12-dodecanedioic acid PA(PACM,12). Investigation into the mechanism of blending revealed that for some polyamides a transamidation reaction improved the blend compatibility. The thermal stability of the biobased PAs depended on which diamine was used. Polymers with aliphatic/aromatic or alicyclic diamines showed no degradation, whereas with fully aromatic diamines such as p-phenylenediamine, some degradation processes were observed under extrusion conditions (260/270 °C).
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http://dx.doi.org/10.3390/polym11030413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473389PMC
March 2019

A Prospective Life Cycle Assessment (LCA) of Monomer Synthesis: Comparison of Biocatalytic and Oxidative Chemistry.

ChemSusChem 2019 Apr 27;12(7):1349-1360. Epub 2019 Feb 27.

Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD, Geleen, The Netherlands.

Biotechnological processes are typically perceived to be greener than chemical processes. A life cycle assessment (LCA) was performed to compare the chemical and biochemical synthesis of lactones obtained by Baeyer-Villiger oxidation. The LCA is prospective (based on experiments at a small scale with primary data) because the process is at an early stage. The results show that the synthesis route has no significant effect on the climate change impact [(1.65±0.59) kg  g vs. (1.64±0.67) kg  g ]. Key process performance metrics affecting the environmental impact were evaluated by performing a sensitivity analysis. Recycling of solvents and enzyme were shown to provide an advantage to the enzymatic synthesis. Additionally, the climate change impact was decreased by 71 % if renewable electricity was used. The study shows that comparative LCAs can be used to usefully support decisions at an early stage of process development.
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http://dx.doi.org/10.1002/cssc.201900007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563695PMC
April 2019

Solvent-Free Method for the Copolymerization of Labile Sugar-Derived Building Blocks into Polyamides.

ACS Sustain Chem Eng 2018 Oct 7;6(10):13504-13517. Epub 2018 Sep 7.

Faculty of Science and Engineering, Biobased Materials, Maastricht University, P.O. Box 616, 6200MD Maastricht, The Netherlands.

This research focuses on the preparation of biobased copolyamides containing biacetalized galactaric acid (GalX), namely, 2,3:4,5-di--isopropylidene-galactaric acid (GalXMe) and 2,3:4,5-di--methylene-galactaric acid (GalXH), in bulk by melt polycondensation of salt monomers. In order to allow the incorporation of temperature-sensitive sugar-derived building blocks into copolyamides at temperatures below the degradation temperature of the monomers and below their melting temperatures, a clever selection of salt monomers is required, such that the sugar-derived salt monomer dissolves in the other salt monomers. The polymerization was investigated by temperature dependent FT-IR and optical microscopy. The structure of the obtained copolyamides was elucidated by NMR and matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) techniques. The positive outcome of this modified polycondensation method depends on the solubility of sugar-derived polyamide salts in polyamide salts of comonomers and the difference between their melting temperatures, however does not depend on the melting temperature of the used sugar-derived monomer. A variety of comonomers was screened in order to establish the underlying mechanisms of the process.
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http://dx.doi.org/10.1021/acssuschemeng.8b03587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179453PMC
October 2018

Toward Upscaled Biocatalytic Preparation of Lactone Building Blocks for Polymer Applications.

Org Process Res Dev 2018 Jul 12;22(7):803-812. Epub 2018 Jun 12.

Aachen-Maastricht Institute for Biobased Materials (AMIBM), Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands.

Although Baeyer-Villiger monooxygenases (BVMOs) have gained attention in recent years, there are few cases of their upscaled application for lactone synthesis. A thermostable cyclohexanone monooxygenase from (TmCHMO) was applied to the oxidation of 3,3,5-trimethylcyclohexanone using a glucose dehydrogenase (GDH) for cofactor regeneration. The reaction progress was improved by optimizing the biocatalyst loading, with investigation into oxygen limitations. The product concentration and productivity were increased by keeping the substrate concentration below the inhibitory level via continuous substrate feeding (CSF). This substrate feeding strategy was evaluated against two biphasic reactions using either toluene or -butyl acetate as immiscible organic solvents. A product concentration of 38 g L and a space-time yield of 1.35 g L h were achieved during the gram-scale synthesis of the two regioisomeric lactones by applying the CSF strategy. These improvements contribute to the large-scale application of BVMOs in the synthesis of branched building blocks for polymer applications.
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http://dx.doi.org/10.1021/acs.oprd.8b00079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156103PMC
July 2018

Elastic materials for tissue engineering applications: Natural, synthetic, and hybrid polymers.

Acta Biomater 2018 10 28;79:60-82. Epub 2018 Aug 28.

Aachen-Maastricht Institute for Biobased Materials (AMIBM), Faculty of Science and Engineering, Maastricht University, Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD Geleen, The Netherlands. Electronic address:

Elastin and collagen are the two main components of elastic tissues and provide the tissue with elasticity and mechanical strength, respectively. Whereas collagen is adequately produced in vitro, production of elastin in tissue-engineered constructs is often inadequate when engineering elastic tissues. Therefore, elasticity has to be artificially introduced into tissue-engineered scaffolds. The elasticity of scaffold materials can be attributed to either natural sources, when native elastin or recombinant techniques are used to provide natural polymers, or synthetic sources, when polymers are synthesized. While synthetic elastomers often lack the biocompatibility needed for tissue engineering applications, the production of natural materials in adequate amounts or with proper mechanical strength remains a challenge. However, combining natural and synthetic materials to create hybrid components could overcome these issues. This review explains the synthesis, mechanical properties, and structure of native elastin as well as the theories on how this extracellular matrix component provides elasticity in vivo. Furthermore, current methods, ranging from proteins and synthetic polymers to hybrid structures that are being investigated for providing elasticity to tissue engineering constructs, are comprehensively discussed.

Statement Of Significance: Tissue engineered scaffolds are being developed as treatment options for malfunctioning tissues throughout the body. It is essential that the scaffold is a close mimic of the native tissue with regards to both mechanical and biological functionalities. Therefore, the production of elastic scaffolds is of key importance to fabricate tissue engineered scaffolds of the elastic tissues such as heart valves and blood vessels. Combining naturally derived and synthetic materials to reach this goal proves to be an interesting area where a highly tunable material that unites mechanical and biological functionalities can be obtained.
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http://dx.doi.org/10.1016/j.actbio.2018.08.027DOI Listing
October 2018

Application of a thermostable Baeyer-Villiger monooxygenase for the synthesis of branched polyester precursors.

J Chem Technol Biotechnol 2018 Aug 16;93(8):2131-2140. Epub 2018 Apr 16.

Maastricht University Aachen-Maastricht Institute for Biobased Materials (AMIBM) Urmonderbaan The Netherlands.

Background: It is widely accepted that the poor thermostability of Baeyer-Villiger monooxygenases limits their use as biocatalysts for applied biocatalysis in industrial applications. The goal of this study was to investigate the biocatalytic oxidation of 3,3,5-trimethylcyclohexanone using a thermostable cyclohexanone monooxygenase from Thermocrispum municipale (TmCHMO) for the synthesis of branched ϵ-caprolactone derivatives as building blocks for tuned polymeric backbones. In this multi-enzymatic reaction, the thermostable cyclohexanone monooxygenase was fused to a phosphite dehydrogenase (PTDH) in order to ensure co-factor regeneration.

Results: Using reaction engineering, the reaction rate and product formation of the regio-isomeric branched lactones were improved and the use of co-solvents and the initial substrate load were investigated. Substrate inhibition and poor product solubility were overcome using continuous substrate feeding regimes, as well as a biphasic reaction system with toluene as water-immiscible organic solvent. A maximum volumetric productivity, or space-time-yield, of 1.20 g L h was achieved with continuous feeding of substrate using methanol as co-solvent, while a maximum product concentration of 11.6 g L was achieved with toluene acting as a second phase and substrate reservoir.

Conclusion: These improvements in key process metrics therefore demonstrate progress towards the up-scaled Baeyer-Villiger monooxygenase-biocatalyzed synthesis of the target building blocks for polymer application. © 2018 The Authors. published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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http://dx.doi.org/10.1002/jctb.5623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055809PMC
August 2018

Quantification of biases in predictions of protein stability changes upon mutations.

Bioinformatics 2018 11;34(21):3659-3665

Department of BioModeling BioInformatics & BioProcesses, Université Libre de Bruxelles, Brussels, Belgium.

Motivation: Bioinformatics tools that predict protein stability changes upon point mutations have made a lot of progress in the last decades and have become accurate and fast enough to make computational mutagenesis experiments feasible, even on a proteome scale. Despite these achievements, they still suffer from important issues that must be solved to allow further improving their performances and utilizing them to deepen our insights into protein folding and stability mechanisms. One of these problems is their bias toward the learning datasets which, being dominated by destabilizing mutations, causes predictions to be better for destabilizing than for stabilizing mutations.

Results: We thoroughly analyzed the biases in the prediction of folding free energy changes upon point mutations (ΔΔG0) and proposed some unbiased solutions. We started by constructing a dataset Ssym of experimentally measured ΔΔG0s with an equal number of stabilizing and destabilizing mutations, by collecting mutations for which the structure of both the wild-type and mutant protein is available. On this balanced dataset, we assessed the performances of 15 widely used ΔΔG0 predictors. After the astonishing observation that almost all these methods are strongly biased toward destabilizing mutations, especially those that use black-box machine learning, we proposed an elegant way to solve the bias issue by imposing physical symmetries under inverse mutations on the model structure, which we implemented in PoPMuSiCsym. This new predictor constitutes an efficient trade-off between accuracy and absence of biases. Some final considerations and suggestions for further improvement of the predictors are discussed.

Supplementary Information: Supplementary data are available at Bioinformatics online.

Note: The article 10.1093/bioinformatics/bty340/, published alongside this paper, also addresses the problem of biases in protein stability change predictions.
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http://dx.doi.org/10.1093/bioinformatics/bty348DOI Listing
November 2018

Structure-Property Relations in New Cyclic Galactaric Acid Derived Monomers and Polymers Therefrom: Possibilities and Challenges.

Macromol Rapid Commun 2018 Jul 14;39(14):e1800077. Epub 2018 Apr 14.

Faculty of Humanities and Sciences, Biobased Materials, Maastricht University, P.O. Box 616, 6200MD, Maastricht, The Netherlands.

In order to fully exploit the potential of carbohydrate-based monomers, different (and some new) functionalities are introduced on galactaric acid via acetalization, and subsequently, partially-biobased polyamides are prepared therefrom via polycondensation in the melt. Compared to nonsubstituted linear monomer, faster advancement of the reaction is observed for the different biacetal derivatives of galactaric acid. This kinetic observation is of great significance since it allows conducting a polymerization reaction at lower temperatures than normally expected for polyamides, which allows overcoming typical challenges (e.g., thermal degradation) encountered upon polymerization of carbohydrate-derived monomers in the melt. The polymers derived from the modified galactaric acid monomers vary in terms of glass transition temperature, thermal stability, hydrophilicity, and functionality.
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http://dx.doi.org/10.1002/marc.201800077DOI Listing
July 2018

Exploring the Substrate Scope of Baeyer-Villiger Monooxygenases with Branched Lactones as Entry towards Polyesters.

Chembiochem 2018 02 29;19(4):354-360. Epub 2017 Nov 29.

Maastricht University, Aachen-Maastricht Institute for Biobased Materials (AMIBM), Brightlands Chemelot Campus, Urmonderbaan 22, 6167 RD, Geleen, The Netherlands.

Baeyer-Villiger monooxygenases (BVMOs) are biocatalysts that are able to convert cyclic ketones into lactones by the insertion of oxygen. The aim of this study was to explore the substrate scope of several BVMOs with (biobased) cyclic ketones as precursors for the synthesis of branched polyesters. The product structure and the degree of conversion of several biotransformations were determined after conversions by using self-sufficient BVMOs. Full regioselectivity towards the normal lactones of jasmatone and menthone was observed, whereas the oxidation of other substrates such as α,β-thujone and 3,3,5-trimethylcyclohexanone resulted in mixtures of regioisomers. This exploration of the substrate scope of both established and newly discovered BVMOs towards biobased ketones contributes to the development of branched polyesters from renewable resources.
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http://dx.doi.org/10.1002/cbic.201700427DOI Listing
February 2018