A bioprinted and scalable model of human tubulo-interstitial kidney fibrosis.

Chronic kidney disease (CKD) affects more than 10% of the global population. As kidney function negatively correlates with the presence of interstitial fibrosis, the development of new anti-fibrotic therapies holds promise to stabilize functional decline in CKD patients. The goal of the study was to generate a scalable bioprinted 3-dimensional kidney tubulo-interstitial disease model of kidney fibrosis.

Varying the Stiffness and Diffusivity of Rod-Shaped Microgels Independently through Their Molecular Building Blocks.

Microgels are water-swollen, crosslinked polymers that are widely used as colloidal building blocks in scaffold materials for tissue engineering and regenerative medicine. Microgels can be controlled in their stiffness, degree of swelling, and mesh size depending on their polymer architecture, crosslink density, and fabrication method-all of which influence their function and interaction with the environment. Currently, there is a lack of understanding of how the polymer composition influences the internal structure of soft microgels and how this morphology affects specific biomedical applications.

Microgels as Platforms for Antibody-Mediated Cytokine Scavenging.

Therapeutic antibodies are the key treatment option for various cytokine-mediated diseases, such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, systemic injection of these antibodies can cause side effects and suppress the immune system. Moreover, clearance of therapeutic antibodies from the blood is limiting their efficacy.

Zwitterionic Dendrimersomes: A Closer Xenobiotic Mimic of Cell Membranes.

Building functional mimics of cell membranes is an important task toward the development of synthetic cells. So far, lipid and amphiphilic block copolymers are the most widely used amphiphiles with the bilayers by the former lacking stability while membranes by the latter are typically characterized by very slow dynamics. Herein, a new type of Janus dendrimer containing a zwitterionic phosphocholine hydrophilic headgroup (JD ) and a 3,5-substituted dihydrobenzoate-based hydrophobic dendron is introduced.

Annealing High Aspect Ratio Microgels into Macroporous 3D Scaffolds Allows for Higher Porosities and Effective Cell Migration.

Growing millimeter-scaled functional tissue remains a major challenge in the field of tissue engineering. Therefore, microporous annealed particles (MAPs) are emerging as promising porous biomaterials that are formed by assembly of microgel building blocks. To further vary the pore size and increase overall MAP porosity of mechanically stable scaffolds, rod-shaped microgels with high aspect ratios up to 20 are chemically interlinked into highly porous scaffolds.

Fibronectin anchoring to viscoelastic poly(dimethylsiloxane) elastomers controls fibroblast mechanosensing and directional motility.

The established link between deregulated tissue mechanics and various pathological states calls for the elucidation of the processes through which cells interrogate and interpret the mechanical properties of their microenvironment. In this work, we demonstrate that changes in the presentation of the extracellular matrix protein fibronectin on the surface of viscoelastic silicone elastomers have an overarching effect on cell mechanosensing, that is independent of bulk mechanics. Reduction of surface hydrophilicity resulted in altered fibronectin adsorption strength as monitored using atomic force microscopy imaging and pulling experiments.

Dendrimersome Synthetic Cells Harbor Cell Division Machinery of Bacteria.

The integration of active cell machinery with synthetic building blocks is the bridge toward developing synthetic cells with biological functions and beyond. Self-replication is one of the most important tasks of living systems, and various complex machineries exist to execute it. In Escherichia coli, a contractile division ring is positioned to mid-cell by concentration oscillations of self-organizing proteins (MinCDE), where it severs membrane and cell wall.

Ionic Combisomes: A New Class of Biomimetic Vesicles to Fuse with Life.

The construction of biomembranes that faithfully capture the properties and dynamic functions of cell membranes remains a challenge in the development of synthetic cells and their application. Here a new concept for synthetic cell membranes based on the self-assembly of amphiphilic comb polymers into vesicles, termed ionic combisomes (i-combisomes) is introduced. These combs consist of a polyzwitterionic backbone to which hydrophobic tails are linked by electrostatic interactions.

Brush-Like Interface on Surface-Attached Hydrogels Repels Proteins and Bacteria.

Interfacing artificial materials with biological tissues remains a challenge. The direct contact of their surface with the biological milieu results in multiscale interactions, in which biomacromolecules adsorb and act as transducers mediating the interactions with cells and tissues. So far, only antifouling polymer brushes have been able to conceal the surface of synthetic materials.

Functionalized Microgel Rods Interlinked into Soft Macroporous Structures for 3D Cell Culture.

In this work, a two component microgel assembly using soft anisometric microgels that interlink to create a 3D macroporous construct for cell growth is reported. Reactive microgel rods with variable aspect ratio are produced via microfluidics in a continuous plug-flow on-chip gelation method by photoinitiated free-radical polymerization of star-polyethylene glycol-acrylate with glycidyl methacrylate or 2-aminoethyl methacrylate comonomers. The resulting complementary epoxy- and amine-functionalized microgels assemble and interlink with each other via a ring opening reaction, resulting in macroporous constructs with pores up to several hundreds of micrometers.

Anisometric Microstructures to Determine Minimal Critical Physical Cues Required for Neurite Alignment.

In nerve regeneration, scaffolds play an important role in providing an artificial extracellular matrix with architectural, mechanical, and biochemical cues to bridge the site of injury. Directed nerve growth is a crucial aspect of nerve repair, often introduced by engineered scaffolds imparting linear tracks. The influence of physical cues, determined by well-defined architectures, has been mainly studied for implantable scaffolds and is usually limited to continuous guiding features.

Unraveling the Mechanism and Kinetics of Binding of an LCI-eGFP-Polymer for Antifouling Coatings.

The ability of proteins to adsorb irreversibly onto surfaces opens new possibilities to functionalize biological interfaces. Herein, the mechanism and kinetics of adsorption of protein-polymer macromolecules with the ability to equip surfaces with antifouling properties are investigated. These macromolecules consist of the liquid chromatography peak I peptide from which antifouling polymer brushes are grafted using single electron transfer-living radical polymerization.

Bicyclic RGD peptides enhance nerve growth in synthetic PEG-based Anisogels.

Nerve regeneration scaffolds often consist of soft hydrogels modified with extracellular matrix (ECM) proteins or fragments, as well as linear and cyclic peptides. One of the commonly used integrin-mediated cell adhesive peptide sequences is Arg-Gly-Asp (RGD). Despite its straightforward coupling mechanisms to artificial extracellular matrix (aECM) constructs, linear RGD peptides suffer from low stability towards degradation and lack integrin selectivity.

Enhanced Concanavalin A Binding to Preorganized Mannose Nanoarrays in Glycodendrimersomes Revealed Multivalent Interactions.

The effect of the two-dimensional glycan display on glycan-lectin recognition remains poorly understood despite the importance of these interactions in a plethora of cellular processes, in (patho)physiology, as well as its potential for advanced therapeutics. Faced with this challenge we utilized glycodendrimersomes, a type of synthetic vesicles whose membrane mimics the surface of a cell and offers a means to probe the carbohydrate biological activity. These single-component vesicles were formed by the self-assembly of sequence-defined mannose-Janus dendrimers, which serve as surrogates for glycolipids.

Substrate Resistance to Traction Forces Controls Fibroblast Polarization.

The mechanics of fibronectin-rich extracellular matrix regulate cell physiology in a number of diseases, prompting efforts to elucidate cell mechanosensing mechanisms at the molecular and cellular scale. Here, the use of fibronectin-functionalized silicone elastomers that exhibit considerable frequency dependence in viscoelastic properties unveiled the presence of two cellular processes that respond discreetly to substrate mechanical properties. Weakly cross-linked elastomers supported efficient focal adhesion maturation and fibroblast spreading because of an apparent stiff surface layer.

How Much Physical Guidance is Needed to Orient Growing Axons in 3D Hydrogels?

Directing cells is essential to organize multi-cellular organisms that are built up from subunits executing specific tasks. This guidance requires a precisely controlled symphony of biochemical, mechanical, and structural signals. While many guiding mechanisms focus on 2D structural patterns or 3D biochemical gradients, injectable material platforms that elucidate how cellular processes are triggered by defined 3D physical guiding cues are still lacking but crucial for the repair of soft tissues.

Unraveling topology-induced shape transformations in dendrimersomes.

The vital functions of cell membranes require their ability to quickly change shape to perform complex tasks such as motion, division, endocytosis, and apoptosis. Membrane curvature in cells is modulated by very complex processes such as changes in lipid composition, the oligomerization of curvature-scaffolding proteins, and the reversible insertion of protein regions that act like wedges in the membrane. But, could much simpler mechanisms support membrane shape transformation? In this work, we demonstrate how the change of amphiphile topology in the bilayer can drive shape transformations of cell membrane models.

Granular Cellulose Nanofibril Hydrogel Scaffolds for 3D Cell Cultivation.

The replacement of diseased and damaged organs remains an challenge in modern medicine. However, through the use of tissue engineering techniques, it may soon be possible to (re)generate tissues and organs using artificial scaffolds. For example, hydrogel networks made from hydrophilic precursor solutions can replicate many properties found in the natural extracellular matrix (ECM) but often lack the dynamic nature of the ECM, as many covalently crosslinked hydrogels possess elastic and static networks with nanoscale pores hindering cell migration without being degradable.

Compartmentalized Jet Polymerization as a High-Resolution Process to Continuously Produce Anisometric Microgel Rods with Adjustable Size and Stiffness.

In the past decade, anisometric rod-shaped microgels have attracted growing interest in the materials-design and tissue-engineering communities. Rod-shaped microgels exhibit outstanding potential as versatile building blocks for 3D hydrogels, where they introduce macroscopic anisometry, porosity, or functionality for structural guidance in biomaterials. Various fabrication methods have been established to produce such shape-controlled elements.

Synthetic 3D PEG-Anisogel Tailored with Fibronectin Fragments Induce Aligned Nerve Extension.

An enzymatically cross-linked polyethylene glycol (PEG)-based hydrogel was engineered to promote and align nerve cells in a three-dimensional manner. To render the injectable, otherwise bioinert, PEG-based material supportive for cell growth, its mechanical and biochemical properties were optimized. A recombinant fibronectin fragment (FNIII9*-10/12-14) was coupled to the PEG backbone during gelation to provide cell adhesive and growth factor binding domains in close vicinity.

Rapid and Robust Coating Method to Render Polydimethylsiloxane Surfaces Cell-Adhesive.

Polydimethylsiloxane (PDMS) is a synthetic material with excellent properties for biomedical applications because of its easy fabrication method, high flexibility, permeability to oxygen, transparency, and potential to produce high-resolution structures in the case of lithography. However, PDMS needs to be modified to support homogeneous cell attachments and spreading. Even though many physical and chemical methods, like plasma treatment or extracellular matrix coatings, have been developed over the last decades to increase cell-surface interactions, these methods are still very time-consuming, often not efficient enough, complex, and can require several treatment steps.

Cellular responses to beating hydrogels to investigate mechanotransduction.

Cells feel the forces exerted on them by the surrounding extracellular matrix (ECM) environment and respond to them. While many cell fate processes are dictated by these forces, which are highly synchronized in space and time, abnormal force transduction is implicated in the progression of many diseases (muscular dystrophy, cancer). However, material platforms that enable transient, cyclic forces in vitro to recreate an in vivo-like scenario remain a challenge.

A Layer-by-Layer Single-Cell Coating Technique To Produce Injectable Beating Mini Heart Tissues via Microfluidics.

Human induced pluripotent stem cells (hiPSCs) are used as an alternative for human embryonic stem cells. Cardiomyocytes derived from hiPSCs are employed in cardiac tissue regeneration constructs due to the heart's low regeneration capacity after infarction. A coculture of hiPSC-CM and primary dermal fibroblasts is encapsulated in injectable poly(ethylene glycol)-based microgels via microfluidics to enhance the efficiency of regenerative cell transplantations.