Mechanically matching the rheological properties of brain tissue for drug-delivery in human glioblastoma models

Parkins, Christopher C.; McAbee, Joseph H.; Ruff, Lisa; Wendler, Astrid; Mair, Richard; Gilbertson, Richard J.; Watts, Colin; Scherman, Oren A.

doi:10.1016/j.biomaterials.2021.120919

Cited by 40 publications

(37 citation statements)

References 29 publications

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“…Lastly, it is well known that GBM and the tumor microenvironment present numerous challenges to adequate and effective delivery of therapeutics, and this concept also extends to the physical properties of the tumor and microenvironment. Recent efforts have included innovative strategies to create therapeutics that account for and accommodate the rheological features to engineer adaptive therapeutics (83). Detailed overview of recent trends and advances in overcoming physical barriers to drug delivery can be found elsewhere (84).…”

Section: Influence Of Microenvironmental Tissue Mechanics On Glioma Malignancymentioning

confidence: 99%

Section: Theranostic Opportunities and Modeling Therapeutic Targetsmentioning

confidence: 99%

“…Alternatively, a therapeutic strategy that alters the mechanical properties of the microenvironment, i.e., manipulating solid stress and fluid stress in the tumor milieu, to engineer an anti-glioma environment may be plausible (71,83,113,144,145). The advantage with such an approach may be the ability to create "smart" or responsive therapies that can either effect mechanical changes locoregionally-in the area of radiographic disease or visible tumor or global changes to target invisible, infiltrative disease (71,83,113,144,145). Many of the studies discussed in this review as well as other studies examining mechanical properties in the cancer microenvironment have used some type of bioengineering approach to create a microenvironmentmimetic substrate to alter the physical forces that are felt by the cell or tissue of interest.…”

Section: Theranostic Opportunities and Modeling Therapeutic Targetsmentioning

confidence: 99%

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Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

et al. 2022

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Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.

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Section: Influence Of Microenvironmental Tissue Mechanics On Glioma Malignancymentioning

confidence: 99%

Section: Theranostic Opportunities and Modeling Therapeutic Targetsmentioning

confidence: 99%

Section: Theranostic Opportunities and Modeling Therapeutic Targetsmentioning

confidence: 99%

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Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

et al. 2022

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“…Overall, there is still much to learn about the mechanical behavior of brain tissue as a whole, and only a limited number of people have studied human brain tissue due to the fact that it is not easily accessible [ 101 , 120 , 121 , 122 , 124 , 127 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 ]. In early research on rheological properties of the brain tissue, Shuck et al showed the differences between gray and white matter [ 121 ].…”

Section: Nanomechanical Properties Of Brain Tissue and Their Signific...mentioning

confidence: 99%

Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers

et al. 2022

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The evaluation of nanomechanical properties of tissues in health and disease is of increasing interest to scientists. It has been confirmed that these properties, determined in part by the composition of the extracellular matrix, significantly affect tissue physiology and the biological behavior of cells, mainly in terms of their adhesion, mobility, or ability to mutate. Importantly, pathophysiological changes that determine disease development within the tissue usually result in significant changes in tissue mechanics that might potentially affect the drug efficacy, which is important from the perspective of development of new therapeutics, since most of the currently used in vitro experimental models for drug testing do not account for these properties. Here, we provide a summary of the current understanding of how the mechanical properties of brain tissue change in pathological conditions, and how the activity of the therapeutic agents is linked to this mechanical state.

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“…Road traffic injuries and severe trauma caused by war or uncontrolled bleeding during surgery are serious threats to human life. Many new materials have been used for rapid wound closure in emergency situations, including fibrin glue, gelatin, collagen, oxidized cellulose, peptides, polymers, and hydrogels. − Among these materials, hydrogels are widely used in tissue repair, wound closure, and other aspects. Polymer hydrogels are a promising option due to their soft properties similar to the extracellular matrix, adjustable physical and chemical properties, and the ability to adapt to a variety of wound shapes. − The self-healing hydrogel can repair itself quickly when cracks appear under force, which ensures the overall mechanical properties of the hydrogel. − However, most conventional hydrogels lack the ability to adhere to moist tissues because the water molecules in the hydrogels tend to reduce the surface energy of the matrix, weakening the ability of the hydrogels to adhere to tissues.…”

Section: Introductionmentioning

confidence: 99%

Highly Adhesive, Conductive, and Self-Healing Hydrogel with Triple Cross-Linking Inspired by Mussel and DNA for Wound Adhesion and Human Motion Sensing

Wang

Yuan

et al. 2021

ACS Appl. Polym. Mater.

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Hydrogel has a similar structure and function as the extracellular matrix and is expected to be used for wound adhesion and hemostasis. However, traditional hydrogels have poor adhesion and no self-healing function, and mechanical properties are also limited. Inspired by mussel and adherent DNA, the triple-crosslinking conductive self-healing hydrogel (CaSA-GAD hydrogel) containing calcium ions (Ca 2+ ), sodium alginate, acrylated guanine, acrylamide, and acrylated dopamine was constructed through UV irradiation, including a G−C pairing hydrogen bond dynamic network, a chemical cross-linking network, and an ionic crosslinking dynamic network. The hydrogel exhibits strong adhesion to various surfaces and peeling properties in the bonding of tissues. With high toughness, the hydrogel can be stretched and compressed without damage. The self-healing property further ensures the mechanical properties of the hydrogel. By loading calcium ions to reduce the impedance of the hydrogel greatly, the wound can be monitored at the same time when the wound is bonded. Both fresh and freeze-dried hydrogel can be used to bond the wound on pork stomach and the scope of application of as wound adhesive increases. In addition, the hydrogel can be used as a sensitive sensor to monitor human movement.

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Mechanically matching the rheological properties of brain tissue for drug-delivery in human glioblastoma models

Cited by 40 publications

References 29 publications

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities

Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers

Highly Adhesive, Conductive, and Self-Healing Hydrogel with Triple Cross-Linking Inspired by Mussel and DNA for Wound Adhesion and Human Motion Sensing

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