Search

Nature uses discrete molecular building blocks to form polymers that assemble into multicomponent, multi-dynamic networks, inside (cytoskeleton) and outside (extracellular matrix) the cell. Both the intra-fibrous molecular dynamics and interactions between fibers dictate (non)linear mechanics, such as stress stiffening and relaxation, and ultimately biological function. Current synthetic systems capture only one dynamic process. Here, we present multi-dynamic hydrogels by uniting a stress-stiffening polymer with supramolecular polymers. Crucial is the molecular dynamics of the supramolecular polymers: They dictate the interaction strength with the stress-stiffening polymer and the subsequent dynamic mechanical properties of the mixed networks. The biological relevance of our multi-dynamic hydrogels is demonstrated by their ability to support fibroblast cell spreading. Future work may address the display of various dynamically presented bioactive cues to cells. [ABSTRACT FROM AUTHOR]

Soluble biochemical agents are being employed to generate kidney organoids from human‐induced pluripotent stem cells. However, this soluble factor approach does not consider the effect of the mechanical environment on lineage commitment. Here, a mechanoresponsive nano‐environment with cell‐adhesive properties composed of supramolecular hydrogelators that co‐assemble into fibrous superstructures to form a transient network is presented, which is used to encapsulate kidney organoids. The delayed sol‐gel transition of the transient network enables fibrous superstructures to diffuse into the densely packed extracellular organoid space during the encapsulation procedure. This allows the mechanoresponsive matrix to induce a biological response beyond the organoid‐hydrogel border, and tune glomerulogenesis inside kidney organoids. In this manner, biomaterials are used as a complementary tool to soluble biochemical agents in tuning lineage commitment and refining organoid maturation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nature uses combined covalent (chemical bonds) and non‐covalent (physical bonds) synthesis in a highly, controlled multi‐step fashion to create functional materials with different mechanical and dynamic properties out of similar building blocks. Surprisingly, this control in fully synthetic systems remains elusive, even though the effects of formulation pathways on the assembly processes have been emphasized—highlighting the importance of and relationship between energy landscapes and function in synthetic systems. Here, we control multiple, coherent supramolecular assembly processes (fiber formation and crosslinking) to formulate hydrogels with tunable mechanical and dynamic properties. Hydrogels are prepared via two different formulation methods using similar building blocks (monofunctional and bifunctional supramolecular monomers), including (1) the mixing of the supramolecular monomers under basic conditions (Fbasic) and (2) the mixing of the supramolecular monomers under neutral conditions (Fneutral). In Fbasic, network formation is induced via simultaneous fiber formation and crosslinking, yielding homogeneously mixed networks which are dense, stiff (~10 kPa) and robust. In Fneutral, network formation is induced through sequential fiber formation and crosslinking, yielding heterogenous, soft (~2 kPa) and dynamic networks. With these results, we advance towards the controlled, multistep, non‐covalent synthesis to create larger hierarchical, functional structures, similar to nature. [ABSTRACT FROM AUTHOR]

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., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

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.

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)