A 3D physio-mimetic interpenetrating network-based platform to decode the pro and anti-tumorigenic properties of cancer-associated fibroblasts

Cao, Huấn; Cheng, Hong Sheng; Wang, Jun Kit; Tan, Nguan Soon; Tay, Chor Yong

doi:10.1016/j.actbio.2021.03.037

Cited by 24 publications

(27 citation statements)

References 48 publications

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“… 325 , 326 In another study, apart from the morphology difference, alginate detachment from CoAl composite hydrogel also triggered mechanics variation of hydrogels, which further led to the reversible phenotypic switch of inhabited cancer-related fibroblasts between inflammatory state (i-state, α-SMA low IL-6 high ) and myofibroblastic (m-state, α-SMA high IL-6 low ) state in cancer-associated fibroblasts. 327 Moreover, the reactive oxygen species (ROS)-HIF1α mechanotransduction signaling axis was recognized as the underlying principle and take responsibility for the phenotypic alteration. To comprehensively understand the influences of biomechanical property variation of hydrogels on cell biology, Caliari et al fabricated a methacrylated hyaluronic acid (MeHA)-based platform whose stiffening would be sequentially varied under visible light irradiation, which was used to study hepatic stellate cell mechano-regulated cellular behaviors during myofibroblasts activation.…”

Section: Influences Of Hydrogel Properties On Cell Behavior and Signaling Pathwaysmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

Self Cite

480

256

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Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.

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Section: Influences Of Hydrogel Properties On Cell Behavior and Signaling Pathwaysmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

Self Cite

480

256

View full text Add to dashboard Cite

show abstract

“…These findings support the conclusion that PAI-1 is, in fact, a major contributor to the drug-resistant phenotype and that targeting PAI-1 function with small-molecule inhibitors may restore chemo-sensitivity. In this regard, the development of the CAF/tumor cell 3D coculture model [ 234 , 235 ] presents an opportunity to identify additional paracrine acting factors and pathways that contribute mechanistically to cancer progression. This system, designed using specified biomaterials and component cell types, approximates the complexity of the in vivo TME.…”

Section: Future Directionsmentioning

confidence: 99%

Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets

Czekay

Cheon

Samarakoon

et al. 2022

Cancers

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Cancer-associated fibroblasts (CAFs) are a heterogenous population of stromal cells found in solid malignancies that coexist with the growing tumor mass and other immune/nonimmune cellular elements. In certain neoplasms (e.g., desmoplastic tumors), CAFs are the prominent mesenchymal cell type in the tumor microenvironment, where their presence and abundance signal a poor prognosis in multiple cancers. CAFs play a major role in the progression of various malignancies by remodeling the supporting stromal matrix into a dense, fibrotic structure while secreting factors that lead to the acquisition of cancer stem-like characteristics and promoting tumor cell survival, reduced sensitivity to chemotherapeutics, aggressive growth and metastasis. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Clarifying the molecular basis for such multidirectional crosstalk among the various normal and neoplastic cell types present in the tumor microenvironment may yield novel targets and new opportunities for therapeutic intervention. This review highlights the most recent concepts regarding the complexity of CAF biology including CAF heterogeneity, functionality in drug resistance, contribution to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.

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“…Alginate can also build an interpenetrating polymer network (IPN) with other hydrogel materials like collagen and dextran to provide even more customized stiffness and multiplexed bioactivity. For example, alginate was incorporated with collagen to generate the IPN with a tunable storage modulus of 49–419 Pa, the variation of which triggered a reversible state of cancer-associated fibroblast between inflammatory state and myofibroblastic state (Cao et al 2021 ).…”

Section: D Bioprinting Technologies and Biomaterialsmentioning

confidence: 99%

3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives

et al. 2022

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The pharmacology and toxicology of a broad variety of therapies and chemicals have significantly improved with the aid of the increasing in vitro models of complex human tissues. Offering versatile and precise control over the cell population, extracellular matrix (ECM) deposition, dynamic microenvironment, and sophisticated microarchitecture, which is desired for the in vitro modeling of complex tissues, 3D bio-printing is a rapidly growing technology to be employed in the field. In this review, we will discuss the recent advancement of printing techniques and bio-ink sources, which have been spurred on by the increasing demand for modeling tactics and have facilitated the development of the refined tissue models as well as the modeling strategies, followed by a state-of-the-art update on the specialized work on cancer, heart, muscle and liver. In the end, the toxicological modeling strategies, substantial challenges, and future perspectives for 3D printed tissue models were explored.

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A 3D physio-mimetic interpenetrating network-based platform to decode the pro and anti-tumorigenic properties of cancer-associated fibroblasts

Cited by 24 publications

References 48 publications

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets

3D bioprinting of complex tissues in vitro: state-of-the-art and future perspectives

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