Laura Rijns

All Publications

• BALANCING SCAFFOLD DEGRADATION AND NEO-TISSUE FORMATION IN IN-SITU TISSUE ENGINEERED VASCULAR GRAFTS. Tissue engineering. Part A Uiterwijk, M., Coolen, B., Rijswijk van, J. W., Söntjens, S., van Houtem, M., Szymczyk, W., Rijns, L., Janssen, H., Wal van der, A., Mol de, B., Bouten, C., Strijkers, G., Dankers, P., Kluin, J. 2024

  Abstract

  An essential aspect of cardiovascular in situ tissue engineering (TE) is to ensure balance between scaffold degradation and neo-tissue formation. We evaluated the degradation velocity and neo-tissue formation of three electrospun supramolecular bisurea-based biodegradable scaffolds that differ in their soft-block backbone compositions only. Scaffolds were implanted as interposition grafts in the abdominal aorta in rats, and evaluated at different time points (t = 1, 6, 12, 24 and 40 weeks) on function, tissue formation, strength and scaffold degradation. The fully carbonate-based biomaterial showed minor degradation after 40 weeks in vivo, while the other two ester-containing biomaterials showed (near) complete degradation within 6 to 12 weeks. Local dilatation was only observed in these faster degrading scaffolds. All materials showed to some extent calcifications, at early as well as late time points. Histological evaluation showed equal and non-native like neo-tissue formation after total degradation. The fully carbonate based scaffolds lagged in neo-tissue formation, presumably as its degradation was (far from) complete at 40 weeks. A significant difference in vessel wall contrast enhancement was observed by MRI between grafts with total compared to minimal degraded scaffolds.

  View details for DOI 10.1089/ten.TEA.2023.0019

  View details for PubMedID 38420632

• Bisurea-Based Supramolecular Polymers for Tunable Biomaterials. Chemistry (Weinheim an der Bergstrasse, Germany) Vleugels, M., Bosman, R., da Camino, P., Wijker, S., Fehér, B., Spiering, J., Rijns, L., Bellan, R., Dankers, P., Palmans, A. R. 2023: e202303361

  Abstract

  Water-soluble supramolecular polymers show great potential to develop dynamic biomaterials with tailored properties. Here, we elucidate the morphology, stability and dynamicity of supramolecular polymers derived from bisurea-based monomers. An accessible synthetic approach from 2,4-toluene diisocyanate (TDI) as the starting material is developed. TDI has two isocyanates that differ in intrinsic reactivity, which allows to obtain functional, desymmetrized monomers in a one-step procedure. We explore how the hydrophobic/hydrophilic ratio affects the properties of the formed supramolecular polymers by increasing the number of methylene units from 10 to 12 keeping the hydrophilic hexa(ethylene glycol) constant. All bisurea-based monomers form long, fibrous structures with 3-5 monomers in the cross-section in water, indicating a proper hydrophobic\hydrophilic balance. The stability of the supramolecular polymers increases with an increasing amount of methylene units, whereas the dynamic nature of the monomers decreases. The introduction of one Cy3 dye affords modified supramolecular monomers, which co-assemble with the unmodified monomers into fibrous structures. All systems show excellent water-compatibility and no toxicity for different cell-lines. Importantly, in cell culture media, the fibrous structures remain present, highlighting the stability of these supramolecular polymers in physiological conditions. The results obtained here motivate further investigation of these bisurea-based building blocks as dynamic biomaterial.

  View details for DOI 10.1002/chem.202303361

  View details for PubMedID 38032693

• Importance of Molecular and Bulk Dynamics in Supramolecular Hydrogels in Dictating Cellular Spreading CHEMISTRY OF MATERIALS Rijns, L., Peeters, J. W., Hendrikse, S. S., Vleugels, M. J., Lou, X., Janssen, H. M., Meijer, E. W., Dankers, P. W. 2023; 35 (19): 8203-8217

  View details for DOI 10.1021/acs.chemmater.3c01676

  View details for Web of Science ID 001069987200001

• Controlled, supramolecular polymer formulation to engineer hydrogels with tunable mechanical and dynamic properties JOURNAL OF POLYMER SCIENCE Rutten, M. A., Rijns, L., Dankers, P. W. 2023

  View details for DOI 10.1002/pol.20230283

  View details for Web of Science ID 001072556800001

• The Importance of Effective Ligand Concentration to Direct Epithelial Cell Polarity in Dynamic Hydrogels. Advanced materials (Deerfield Beach, Fla.) Rijns, L., Hagelaars, M. J., van der Tol, J. J., Loerakker, S., Bouten, C. V., Dankers, P. Y. 2023: e2300873

  Abstract

  Epithelial cysts and organoids are multicellular hollow structures formed by correctly polarized epithelial cells. Important in steering these cysts from single cells is the dynamic regulation of extracellular matrix presented ligands, and matrix dynamics. Here, control over the effective ligand concentration is introduced, decoupled from bulk and local mechanical properties, in synthetic dynamic supramolecular hydrogels formed through noncovalent crosslinking of supramolecular fibers. Control over the effective ligand concentration is realized by 1) keeping the ligand concentration constant, but changing the concentration of nonfunctionalized molecules or by 2) varying the ligand concentration, while keeping the concentration of non-functionalized molecules constant. The results show that in 2D, the effective ligand concentration within the supramolecular fibers rather than gel stiffness (from 0.1 to 8 kPa) regulates epithelial polarity. In 3D, increasing the effective ligand concentration from 0.5 × 10-3 to 2 × 10-3 m strengthens the effect of increased gel stiffness from 0.1 to 2 kPa, to synergistically yield more correctly polarized cysts. Through integrin manipulation, it is shown that epithelial polarity is regulated by tension-based homeostasis between cells and matrix. The results reveal the effective ligand concentration as influential factor in regulating epithelial polarity and provide insights on engineering of synthetic biomaterials for cell and organoid culture.

  View details for DOI 10.1002/adma.202300873

  View details for PubMedID 37264535

• Engineering Strategies to Move from Understanding to Steering Renal Tubulogenesis. Tissue engineering. Part B, Reviews Hagelaars, M. J., Rijns, L., Dankers, P. Y., Loerakker, S., Bouten, C. V. 2023; 29 (3): 203-216

  Abstract

  Rebuilding the kidney in the context of tissue engineering offers a major challenge as the organ is structurally complex and has a high variety of specific functions. Recreation of kidney function is inherently connected to the formation of tubules since the functional subunit of the kidney, the nephron, is based on tubular structures. In vivo, tubulogenesis culminates in a perfectly shaped, patterned, and functional renal tubule via different morphogenic processes that depend on delicately orchestrated chemical, physical, and mechanical interactions between cells and between cells and their microenvironment. This review summarizes the current understanding of the role of the microenvironment in the morphogenic processes involved in in vivo renal tubulogenesis. We highlight the current state-of-the-art of renal tubular engineering and provide a view on the design elements that can be extracted from these studies. Next, we discuss how computational modeling can aid in specifying and identifying design parameters and provide directions on how these design parameters can be incorporated in biomaterials for the purpose of engineering renal tubulogenesis. Finally, we propose that a step-by-step reciprocal interaction between understanding and engineering is necessary to effectively guide renal tubulogenesis. Impact statement Tubular tissue engineering lies at the foundation of regenerating kidney tissue function, as the functional subunit of the kidney, the nephron, is based on tubular structures. Guiding renal tubulogenesis toward functional renal tubules requires in-depth knowledge of the developmental processes that lead to the formation of native tubules as well as engineering approaches to steer these processes. In this study, we review the role of the microenvironment in the developmental processes that lead to functional renal tubules and give directions how this knowledge can be harnessed for biomaterial-based tubular engineering using computational models.

  View details for DOI 10.1089/ten.TEB.2022.0120

  View details for PubMedID 36173101

• Introducing carbohydrate patterning in mannose-decorated supramolecular assemblies and hydrogels. Chemical communications (Cambridge, England) Rijns, L., Su, L., Maxeiner, K., Morgese, G., Ng, D. Y., Weil, T., Dankers, P. Y. 2023; 59 (15): 2090-2093

  Abstract

  Benzene-1,3,5-tricarboxamide (BTA) glyco-monomers containing one, two or three mannose units are synthesized and formulated into differently patterned supramolecular glycopolymers through homo-assembly or co-assembly with non-functionalized BTAs. Unfortunately, no cellular activity could be detected. Excitingly, these glyco-BTA monomers could be formulated into hydrogels, paving the way for (immune) cell culture.

  View details for DOI 10.1039/d2cc06064g

  View details for PubMedID 36723198

  View details for PubMedCentralID PMC9933453

• Engineered hydrogels for mechanobiology NATURE REVIEWS METHODS PRIMERS Blache, U., Ford, E. M., Ha, B., Rijns, L., Chaudhuri, O., Dankers, P. W., Kloxin, A. M., Snedeker, J. G., Gentleman, E. 2022; 2 (1)

  View details for DOI 10.1038/s43586-022-00179-7

  View details for Web of Science ID 000899042600002

• Towards understanding the messengers of extracellular space: Computational models of outside-in integrin reaction networks. Computational and structural biotechnology journal Karagöz, Z., Rijns, L., Dankers, P. Y., van Griensven, M., Carlier, A. 2021; 19: 303-314

  Abstract

  The interactions between cells and their extracellular matrix (ECM) are critically important for homeostatic control of cell growth, proliferation, differentiation and apoptosis. Transmembrane integrin molecules facilitate the communication between ECM and the cell. Since the characterization of integrins in the late 1980s, there has been great advancement in understanding the function of integrins at different subcellular levels. However, the versatility in molecular pathways integrins are involved in, the high diversity in their interaction partners both outside and inside the cell as well as on the cell membrane and the short lifetime of events happening at the cell-ECM interface make it difficult to elucidate all the details regarding integrin function experimentally. To overcome the experimental challenges and advance the understanding of integrin biology, computational modeling tools have been used extensively. In this review, we summarize the computational models of integrin signaling while we explain the function of integrins at three main subcellular levels (outside the cell, cell membrane, cytosol). We also discuss how these computational modeling efforts can be helpful in other disciplines such as biomaterial design. As such, this review is a didactic modeling summary for biomaterial researchers interested in complementing their experimental work with computational tools or for seasoned computational scientists that would like to advance current in silico integrin models.

  View details for DOI 10.1016/j.csbj.2020.12.025

  View details for PubMedID 33425258

  View details for PubMedCentralID PMC7779863