A Microfluidic Blood Brain Barrier Model to Study the Influence of Glioblastoma Tumor Cells on BBB Function

Small, Год журнала: 2025, Номер unknown

Опубликована: Апрель 4, 2025

The blood brain barrier (BBB) plays an essential role in regulating function by controlling the transport of nutrients and preventing toxins from moving rest body's circulation into brain. Because it is more selective than most other endothelial barriers, many therapeutic candidates fail to cross BBB, making difficult design novel drugs treat pathologies In addition, BBB dysfunction observed diseases including glioblastoma (GB), aggressive, universally fatal primary tumor. Here, a 3D microfluidic model designed using human cells brain-mimetic hydrogel. vitro replicates several key functions BBB. This system has low permeability small molecules responds inflammatory cues. addition GB reveals that changes tumor-cell-population-dependent manner. Some cell populations lead increased diffusive while others induce immune binding. Together, these results indicate this can be used investigate disease progression drug delivery GB.

Язык: Английский

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Multi‐Functional Gelatin‐Dithiolane Hydrogels for Tissue Engineering

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Abstract Biomaterials that integrate multiple functionalities, mimic the extracellular matrix (ECM) microenvironment to support cellular growth, and adhere robustly damaged tissues are highly needed advance tissue engineering. Protein‐based biomaterials promising due their inherent biocompatibility, biomimicry, biodegradation, cell‐supportive properties. Herein, by leveraging unique ability of dithiolanes generate on‐demand in situ thiols, a new class dithiolane‐modified, protein‐based biomaterial combines unique, seemingly opposing functions for engineering is developed. Dithiolane‐modified gelatin, model protein used herein, enabled photoinitiator‐free photo‐crosslinking form multi‐functional gelatin‐dithiolane (GelDT) hydrogels, which displayed exceptional long‐term stability cell culture media (>28 days) growth both surface‐seeded encapsulated cells. GelDT hydrogels allowed pre‐gelation tuning biomechanical properties biodegradation via introducing physical crosslinks, post‐gelation stress‐relaxation rate, responding exogenous independently other parameters. Furthermore, covalent immobilization bio‐active molecules, glutathione‐responsive drug release, supported efficient 3D bioprinting its shear‐thinning ability, demonstrated robust adhesion various contexts (bare skin, ex‐vivo, in‐vivo) disulfide coupling with endogenous thiols. Together, this study presents novel multi‐responsive biomaterial, anticipated regeneration.

Язык: Английский

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A Library of Elastin-like Proteins with Tunable Matrix Ligands for In Vitro 3D Neural Cell Culture

Biomacromolecules, Год журнала: 2023, Номер 24(12), С. 5926 - 5939

Опубликована: Ноя. 21, 2023

Hydrogels with encapsulated cells have widespread biomedical applications, both as tissue-mimetic 3D cultures in vitro and tissue-engineered therapies vivo. Within these hydrogels, the presentation of cell-instructive extracellular matrix (ECM)-derived ligands stiffness are critical factors known to influence numerous cell behaviors. While individual ECM biopolymers can be blended together alter ligands, this typically results hydrogels a range mechanical properties. Synthetic systems that allow for facile incorporation modulation multiple without modification mechanics highly desirable. In present work, we leverage protein engineering design family xeno-free (i.e., devoid animal-derived components) consisting recombinant hyaluronan elastin-like proteins (ELPs), cross-linked dynamic covalent bonds. The ELP components incorporate peptide derived from proteins, including fibronectin (RGD), laminin (IKVAV YIGSR), collagen (DGEA), tenascin-C (PLAEIDGIELTY VFDNFVL). By carefully designing primary sequence, form defined tunable concentrations similar mechanics. Utilizing system, demonstrate neurite outgrowth embryonic dorsal root ganglion (DRG) is significantly modified by ligand content. Thus, library protein-engineered cell-compatible system systematically study responses matrix-derived ligands.

Язык: Английский

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Substrate stress relaxation regulates neural stem cell fate commitment

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(28)

Опубликована: Июль 5, 2024

Adult neural stem cells (NSCs) reside in the dentate gyrus of hippocampus, and their capacity to generate neurons glia plays a role learning memory. In addition, neurodegenerative diseases are known be caused by loss glial cells, resulting need better understand cell fate commitment processes. We previously showed that NSC toward neuronal or lineage is strongly influenced extracellular matrix stiffness, property elastic materials. However, tissues vivo not purely have varying degrees viscous character. Relatively little about how viscoelastic properties substrate impact commitment. Here, we introduce polyacrylamide-based culture platform incorporates mismatched DNA oligonucleotide-based cross-links as well covalent cross-links. This allows for tunable stress relaxation via variation number base pairs. find NSCs exhibit increased astrocytic differentiation degree increased. Furthermore, culturing on increasingly stress-relaxing substrates impacts cytoskeletal dynamics decreasing intracellular actin flow rates stimulating cyclic activation mechanosensitive protein RhoA. Additionally, inhibition motor–clutch model components such myosin II focal adhesion kinase partially completely reverts distributions observed substrates. Collectively, our results unique system controlling offer insight into integrate cues direct

Язык: Английский

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Viscoelasticity of Hyaluronic Acid Hydrogels Regulates Human Pluripotent Stem Cell‐derived Spinal Cord Organoid Patterning and Vascularization

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Сен. 19, 2024

Abstract Recently, it has been recognized that natural extracellular matrix (ECM) and tissues are viscoelastic, while only elastic properties have investigated in the past. How viscoelastic regulates stem cell patterning is critical for cell‐ECM mechano‐transduction. Here, this study fabricated different methacrylated hyaluronic acid (HA) hydrogels using covalent cross–linking, consisting of two gels with similar elasticity (stiffness) but viscoelasticity, viscoelasticity (stiffness). Meanwhile, a second set dual network containing both coordinated cross–links. Human spinal cord organoid (hSCO) HA co‐culture isogenic human blood vessel organoids (hBVOs) investigated. The promote regional hSCO compared to hydrogels. More can dorsal marker expression, softer result higher interneuron expression. effects become more dominant than stiffness hSCOs hBVOs. In addition, lead Yes‐associated protein nuclear translocation, revealing mechanism This research provides insights into behaviors during ECM‐mimicking vitro microenvironments applications regenerative medicine.

Язык: Английский

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