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2. Exploring silk fibroin aerogels via different coagulation approaches

Author

Zorgeenheid Orthopaedie Medisch, Orthopaedie Onderzoek, Viola, Martina, Chartier, Coraline, Mihajlovic, Marko, Buwalda, Sijtze, Pradille, Christophe, Budtova, Tatiana, Vermonden, Tina, Zorgeenheid Orthopaedie Medisch, Orthopaedie Onderzoek, Viola, Martina, Chartier, Coraline, Mihajlovic, Marko, Buwalda, Sijtze, Pradille, Christophe, Budtova, Tatiana, and Vermonden, Tina

Published
2024

3. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Experimentele Afd. Cardiologie 2, Regenerative Medicine and Stem Cells, Orthopaedie Onderzoek, Team Medisch, Circulatory Health, Onderzoek Cardiovasculair Reg. Med., Onderzoek Algemene Cardiologie, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Published
2024

4. Hypothermic and cryogenic preservation of cardiac tissue-engineered constructs

Author

Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, van Mil, Alain, Janssen, Jasmijn, Chirico, Nino, Ainsworth, Madison J, Cedillo-Servin, Gerardo, Viola, Martina, Dokter, Inge, Vermonden, Tina, Doevendans, Pieter A, Serra, Margarida, Voets, Ilja K, Malda, Jos, Castilho, Miguel, van Laake, Linda W, Sluijter, Joost P G, Sampaio-Pinto, Vasco, and van Mil, Alain

Abstract

Cardiac tissue engineering (cTE) has already advanced towards the first clinical trials, investigating safety and feasibility of cTE construct transplantation in failing hearts. However, the lack of well-established preservation methods poses a hindrance to further scalability, commercialization, and transportation, thereby reducing their clinical implementation. In this study, hypothermic preservation (4 °C) and two methods for cryopreservation ( i.e., a slow and fast cooling approach to -196 °C and -150 °C, respectively) were investigated as potential solutions to extend the cTE construct implantation window. The cTE model used consisted of human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts embedded in a natural-derived hydrogel and supported by a polymeric melt electrowritten hexagonal scaffold. Constructs, composed of cardiomyocytes of different maturity, were preserved for three days, using several commercially available preservation protocols and solutions. Cardiomyocyte viability, function (beat rate and calcium handling), and metabolic activity were investigated after rewarming. Our observations show that cardiomyocytes' age did not influence post-rewarming viability, however, it influenced construct function. Hypothermic preservation with HypoThermosol® ensured cardiomyocyte viability and function. Furthermore, fast freezing outperformed slow freezing, but both viability and function were severely reduced after rewarming. In conclusion, whereas long-term preservation remains a challenge, hypothermic preservation with HypoThermosol® represents a promising solution for cTE construct short-term preservation and potential transportation, aiding in off-the-shelf availability, ultimately increasing their clinical applicability.

Published
2024

5. Covalent Grafting of Functionalized MEW Fibers to Silk Fibroin Hydrogels to Obtain Reinforced Tissue Engineered Constructs

Author

Afd Pharmaceutics, Equine Musculoskeletal Biology, CS_Locomotion, Locomotion - Equine Sciences, Viola, Martina, Ainsworth, Madison J, Mihajlovic, Marko, Cedillo-Servin, Gerardo, van Steenbergen, Mies J, van Rijen, Mattie, de Ruijter, Mylène, Castilho, Miguel, Malda, Jos, Vermonden, Tina, Afd Pharmaceutics, Equine Musculoskeletal Biology, CS_Locomotion, Locomotion - Equine Sciences, Viola, Martina, Ainsworth, Madison J, Mihajlovic, Marko, Cedillo-Servin, Gerardo, van Steenbergen, Mies J, van Rijen, Mattie, de Ruijter, Mylène, Castilho, Miguel, Malda, Jos, and Vermonden, Tina

Published
2024

6. Covalent Grafting of Functionalized MEW Fibers to Silk Fibroin Hydrogels to Obtain Reinforced Tissue Engineered Constructs

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Viola, Martina, Ainsworth, Madison J., Mihajlovic, Marko, Cedillo-Servin, Gerardo, van Steenbergen, Mies J., van Rijen, Mattie, de Ruijter, Mylène, Castilho, Miguel, Malda, Jos, Vermonden, Tina, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Viola, Martina, Ainsworth, Madison J., Mihajlovic, Marko, Cedillo-Servin, Gerardo, van Steenbergen, Mies J., van Rijen, Mattie, de Ruijter, Mylène, Castilho, Miguel, Malda, Jos, and Vermonden, Tina

Published
2024

8. Exploring silk fibroin aerogels via different coagulation approaches

Author

Afd Pharmaceutics, Pharmaceutics, Viola, Martina, Chartier, Coraline, Mihajlovic, Marko, Buwalda, Sijtze, Pradille, Christophe, Budtova, Tatiana, Vermonden, Tina, Afd Pharmaceutics, Pharmaceutics, Viola, Martina, Chartier, Coraline, Mihajlovic, Marko, Buwalda, Sijtze, Pradille, Christophe, Budtova, Tatiana, and Vermonden, Tina

Published
2024

10. Stimuli-Responsive Hydrogels: The Dynamic Smart Biomaterials of Tomorrow

Author

Neumann, Myriam, di Marco, Greta, Iudin, Dmitrii, Viola, Martina, van Nostrum, Cornelus F., van Ravensteijn, Bas G.P., Vermonden, Tina, Neumann, Myriam, di Marco, Greta, Iudin, Dmitrii, Viola, Martina, van Nostrum, Cornelus F., van Ravensteijn, Bas G.P., and Vermonden, Tina

Abstract

In the past decade, stimuli-responsive hydrogels are increasingly studied as biomaterials for tissue engineering and regenerative medicine purposes. Smart hydrogels can not only replicate the physicochemical properties of the extracellular matrix but also mimic dynamic processes that are crucial for the regulation of cell behavior. Dynamic changes can be influenced by the hydrogel itself (isotropic vs anisotropic) or guided by applying localized triggers. The resulting swelling-shrinking, shape-morphing, as well as patterns have been shown to influence cell function in a spatiotemporally controlled manner. Furthermore, the use of stimuli-responsive hydrogels as bioinks in 4D bioprinting is very promising as they allow the biofabrication of complex microstructures. This perspective discusses recent cutting-edge advances as well as current challenges in the field of smart biomaterials for tissue engineering. Additionally, emerging trends and potential future directions are addressed.

Published
2023

11. Release Kinetics of Dexamethasone Phosphate from Porous Chitosan: Comparison of Aerogels and Cryogels

Author

Chartier, Coraline, Buwalda, Sytze, Ilochonwu, Blessing C., Van Den Berghe, Hélène, Bethry, Audrey, Vermonden, Tina, Viola, Martina, Nottelet, Benjamin, Budtova, Tatiana, Chartier, Coraline, Buwalda, Sytze, Ilochonwu, Blessing C., Van Den Berghe, Hélène, Bethry, Audrey, Vermonden, Tina, Viola, Martina, Nottelet, Benjamin, and Budtova, Tatiana

Abstract

Porous chitosan materials as potential wound dressings were prepared via dissolution of chitosan, nonsolvent-induced phase separation in NaOH-water, formation of a hydrogel, and either freeze-drying or supercritical CO2 drying, leading to “cryogels” and “aerogels”, respectively. The hydrophilic drug dexamethasone sodium phosphate was loaded by impregnation of chitosan hydrogel, and the release from cryogel or aerogel was monitored at two pH values relevant for wound healing. The goal was to compare the drug-loading efficiency and release behavior from aerogels and cryogels as a function of the drying method, the materials’ physicochemical properties (density, morphology), and the pH of the release medium. Cryogels exhibited a higher loading efficiency and a faster release in comparison with aerogels. A higher sample density and lower pH value of the release medium resulted in a more sustained release in the case of aerogels. In contrast, for cryogels, the density and pH of the release medium did not noticeably influence release kinetics. The Korsmeyer-Peppas model showed the best fit to describe the release from the porous chitosan materials into the different media.

Published
2023

12. Microstructured silk-fiber scaffolds with enhanced stretchability

Author

Afd Pharmaceutics, Afd Pharmacology, Pharmaceutics, Pharmacology, Locomotion - Equine Sciences, Viola, Martina, Cedillo-Servin, Gerardo, van Genderen, Anne Metje, Imhof, Isabella, Vena, Paula, Mihajlovic, Marko, Piluso, Susanna, Malda, Jos, Vermonden, Tina, Castilho, Miguel, Afd Pharmaceutics, Afd Pharmacology, Pharmaceutics, Pharmacology, Locomotion - Equine Sciences, Viola, Martina, Cedillo-Servin, Gerardo, van Genderen, Anne Metje, Imhof, Isabella, Vena, Paula, Mihajlovic, Marko, Piluso, Susanna, Malda, Jos, Vermonden, Tina, and Castilho, Miguel

Published
2023

13. Stimuli-Responsive Hydrogels: The Dynamic Smart Biomaterials of Tomorrow

Author

Afd Pharmaceutics, Pharmaceutics, Neumann, Myriam, di Marco, Greta, Iudin, Dmitrii, Viola, Martina, van Nostrum, Cornelus F., van Ravensteijn, Bas G.P., Vermonden, Tina, Afd Pharmaceutics, Pharmaceutics, Neumann, Myriam, di Marco, Greta, Iudin, Dmitrii, Viola, Martina, van Nostrum, Cornelus F., van Ravensteijn, Bas G.P., and Vermonden, Tina

Published
2023

14. Release Kinetics of Dexamethasone Phosphate from Porous Chitosan: Comparison of Aerogels and Cryogels

Author

Afd Pharmaceutics, Pharmaceutics, Chartier, Coraline, Buwalda, Sytze, Ilochonwu, Blessing C., Van Den Berghe, Hélène, Bethry, Audrey, Vermonden, Tina, Viola, Martina, Nottelet, Benjamin, Budtova, Tatiana, Afd Pharmaceutics, Pharmaceutics, Chartier, Coraline, Buwalda, Sytze, Ilochonwu, Blessing C., Van Den Berghe, Hélène, Bethry, Audrey, Vermonden, Tina, Viola, Martina, Nottelet, Benjamin, and Budtova, Tatiana

Published
2023

15. Viscoelastic Chondroitin Sulfate and Hyaluronic Acid Double-Network Hydrogels with Reversible Cross-Links

Author

Mihajlovic, Marko, Rikkers, Margot, Mihajlovic, Milos, Viola, Martina, Schuiringa, Gerke, Ilochonwu, Blessing C., Masereeuw, Rosalinde, Vonk, Lucienne, Malda, Jos, Ito, Keita, Vermonden, Tina, Pharmaceutics, Pharmacology, Afd Pharmaceutics, Afd Pharmacology, Equine Musculoskeletal Biology, dES RMSC, Pharmaceutical and Pharmacological Sciences, Pharmaceutics, Pharmacology, Afd Pharmaceutics, Afd Pharmacology, Equine Musculoskeletal Biology, dES RMSC, Supramolecular Polymer Chemistry, Orthopaedic Biomechanics, and Eindhoven MedTech Innovation Center

Subjects
Polymers and Plastics, Tissue Engineering, Chondroitin Sulfates, Bioprinting, Hydrazones, Bioengineering, Hydrogels, Biocompatible Materials, Hydrogels/chemistry, Biomaterials, Hyaluronic Acid/chemistry, Materials Chemistry, Chondroitin Sulfates/chemistry, Hyaluronic Acid
Abstract

Viscoelastic hydrogels are gaining interest as they possess necessary requirements for bioprinting and injectability. By means of reversible, dynamic covalent bonds, it is possible to achieve features that recapitulate the dynamic character of the extracellular matrix. Dually cross-linked and double-network (DN) hydrogels seem to be ideal for the design of novel biomaterials and bioinks, as a wide range of properties required for mimicking advanced and complex tissues can be achieved. In this study, we investigated the fabrication of chondroitin sulfate/hyaluronic acid (CS/HA)-based DN hydrogels, in which two networks are interpenetrated and cross-linked with the dynamic covalent bonds of very different lifetimes. Namely, Diels-Alder adducts (between methylfuran and maleimide) and hydrazone bonds (between aldehyde and hydrazide) were chosen as cross-links, leading to viscoelastic hydrogels. Furthermore, we show that viscoelasticity and the dynamic character of the resulting hydrogels could be tuned by changing the composition, that is, the ratio between the two types of cross-links. Also, due to a very dynamic nature and short lifetime of hydrazone cross-links (∼800 s), the DN hydrogel is easily processable (e.g., injectable) in the first stages of gelation, allowing the material to be used in extrusion-based 3D printing. The more long-lasting and robust Diels-Alder cross-links are responsible for giving the network enhanced mechanical strength and structural stability. Being highly charged and hydrophilic, the cross-linked CS and HA enable a high swelling capacity (maximum swelling ratio ranging from 6 to 12), which upon confinement results in osmotically stiffened constructs, able to mimic the mechanical properties of cartilage tissue, with the equilibrium moduli ranging from 0.3 to 0.5 MPa. Moreover, the mesenchymal stromal cells were viable in the presence of the hydrogels, and the effect of the degradation products on the macrophages suggests their safe use for further translational applications. The DN hydrogels with dynamic covalent cross-links hold great potential for the development of novel smart and tunable viscoelastic materials to be used as biomaterial inks or bioinks in bioprinting and regenerative medicine.

Published
2022

16. SILK-BASED MATERIALS TO CREATE HIGH RESOLUTION THREE-DIMENSIONAL STRUCTURES USING ELECTROHYDRODYNAMIC PRINTING

Author

Viola, Martina, Piluso, Susanna, Mihajlovic, Marko, Malda, Jos, Castilho, Miguel, Vermonden, Tina, Viola, Martina, Piluso, Susanna, Mihajlovic, Marko, Malda, Jos, Castilho, Miguel, and Vermonden, Tina

Abstract

Mimicking the complex hierarchical structure of the extracellular matrix (ECM) has always been a major goal in tissue engineering (TE) approaches [1] [2]. Despite the great advances in biomaterial processing technologies, the main limitation concerns the resolution of the fibers, which hampers the reproduction of ECM. Here, we combine Silk Fibroin (SF) [5], a highly potent biomaterial that intrinsically has the characteristics of making fibrous structures, with Electrohydrodynamic printing, an innovative 3D printing technique that allows patterning at micro and sub micro scale. To fabricate these complex structures, Electrohydrodynamic printing applies a voltage between the needle and the collector screen to charge the polymer solution, with a consequent thinning of the fibers, making it possible to reach optimal resolutions for recreating the hierarchical and fibrillar structure of ECM [3] [4]. We have studied SF in its chemical structure to allow a better understanding of the structural and mechanical behaviour of the material before and after printing. We have demonstrated the printability of SF with Electrohydrodynamic printing and, just by tuning the rheological properties, it is possible to obtain straight fibers with a resolution of 10‐20 mm. We have also demonstrated that these fibers can be physically crosslinked inducing the formation of b‐sheets structure in the protein chain; after crosslinking the fibers are stable and don't dissolve in water. SF is therefore proving to be an optimal material for this application and is gaining strong interest in soft tissue engineering.

Published
2022

17. Gold Nanoclusters: Imaging, Therapy, and Theranostic Roles in Biomedical Applications

Author

van de Looij, Sanne M., Hebels, Erik R., Viola, Martina, Hembury, Mathew, Oliveira, Sabrina, Vermonden, Tina, van de Looij, Sanne M., Hebels, Erik R., Viola, Martina, Hembury, Mathew, Oliveira, Sabrina, and Vermonden, Tina

Abstract

For the past two decades, atomic gold nanoclusters (AuNCs, ultrasmall clusters of several to 100 gold atoms, having a total diameter of <2 nm) have emerged as promising agents in the diagnosis and treatment of cancer. Owing to their small size, significant quantization occurs to their conduction band, which leads to emergent photonic properties and the disappearance of the plasmonic responses observed in larger gold nanoparticles. For example, AuNCs exhibit native luminescent properties, which have been well-explored in the literature. Using proteins, peptides, or other biomolecules as structural scaffolds or capping ligands, required for the stabilization of AuNCs, improves their biocompatibility, while retaining their distinct optical properties. This paved the way for the use of AuNCs in fluorescent bioimaging, which later developed into multimodal imaging combined with computer tomography and magnetic resonance imaging as examples. The development of AuNC-based systems for diagnostic applications in cancer treatment was then made possible by employing active or passive tumor targeting strategies. Finally, the potential therapeutic applications of AuNCs are extensive, having been used as light-activated and radiotherapy agents, as well as nanocarriers for chemotherapeutic drugs, which can be bound to the capping ligand or directly to the AuNCs via different mechanisms. In this review, we present an overview of the diverse biomedical applications of AuNCs in terms of cancer imaging, therapy, and combinations thereof, as well as highlighting some additional applications relevant to biomedical research.

Published
2022

19. Viscoelastic Chondroitin Sulfate and Hyaluronic Acid Double-Network Hydrogels with Reversible Cross-Links

Author

Pharmaceutics, Pharmacology, Afd Pharmaceutics, Afd Pharmacology, Equine Musculoskeletal Biology, dES RMSC, Mihajlovic, Marko, Rikkers, Margot, Mihajlovic, Milos, Viola, Martina, Schuiringa, Gerke, Ilochonwu, Blessing C., Masereeuw, Rosalinde, Vonk, Lucienne, Malda, Jos, Ito, Keita, Vermonden, Tina, Pharmaceutics, Pharmacology, Afd Pharmaceutics, Afd Pharmacology, Equine Musculoskeletal Biology, dES RMSC, Mihajlovic, Marko, Rikkers, Margot, Mihajlovic, Milos, Viola, Martina, Schuiringa, Gerke, Ilochonwu, Blessing C., Masereeuw, Rosalinde, Vonk, Lucienne, Malda, Jos, Ito, Keita, and Vermonden, Tina

Published
2022

21. Viscoelastic Chondroitin Sulfate and Hyaluronic Acid Double-Network Hydrogels with Reversible Cross-Links

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Mihajlovic, Marko, Rikkers, Margot, Mihajlovic, Milos, Viola, Martina, Schuiringa, Gerke, Ilochonwu, Blessing C., Masereeuw, Rosalinde, Vonk, Lucienne, Malda, Jos, Ito, Keita, Vermonden, Tina, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Mihajlovic, Marko, Rikkers, Margot, Mihajlovic, Milos, Viola, Martina, Schuiringa, Gerke, Ilochonwu, Blessing C., Masereeuw, Rosalinde, Vonk, Lucienne, Malda, Jos, Ito, Keita, and Vermonden, Tina

Published
2022

22. The Importance of Interfaces in Multi-Material Biofabricated Tissue Structures

Author

Viola, Martina, Piluso, Susanna, Groll, Jürgen, Vermonden, Tina, Malda, Jos, Castilho, Miguel, Viola, Martina, Piluso, Susanna, Groll, Jürgen, Vermonden, Tina, Malda, Jos, and Castilho, Miguel

Abstract

Biofabrication exploits additive manufacturing techniques for creating 3D structures with a precise geometry that aim to mimic a physiological cellular environment and to develop the growth of native tissues. The most recent approaches of 3D biofabrication integrate multiple technologies into a single biofabrication platform combining different materials within different length scales to achieve improved construct functionality. However, the importance of interfaces between the different material phases, has not been adequately explored. This is known to determine material's interaction and ultimately mechanical and biological performance of biofabricated parts. In this review, this gap is bridged by critically examining the interface between different material phases in (bio)fabricated structures, with a particular focus on how interfacial interactions can compromise or define the mechanical (and biological) properties of the engineered structures. It is believed that the importance of interfacial properties between the different constituents of a composite material, deserves particular attention in its role in modulating the final characteristics of 3D tissue-like structures.

Published
2021

23. The Importance of Interfaces in Multi-Material Biofabricated Tissue Structures

Author

Afd Pharmaceutics, Equine Musculoskeletal Biology, dES RMSC, Pharmaceutics, Viola, Martina, Piluso, Susanna, Groll, Jürgen, Vermonden, Tina, Malda, Jos, Castilho, Miguel, Afd Pharmaceutics, Equine Musculoskeletal Biology, dES RMSC, Pharmaceutics, Viola, Martina, Piluso, Susanna, Groll, Jürgen, Vermonden, Tina, Malda, Jos, and Castilho, Miguel

Published
2021

24. The Importance of Interfaces in Multi-Material Biofabricated Tissue Structures

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Other research (not in main researchprogram), Viola, Martina, Piluso, Susanna, Groll, Jürgen, Vermonden, Tina, Malda, Jos, Castilho, Miguel, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Other research (not in main researchprogram), Viola, Martina, Piluso, Susanna, Groll, Jürgen, Vermonden, Tina, Malda, Jos, and Castilho, Miguel

Published
2021

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