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Cancer Cell Biology in Biological Hydrogel

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A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Processing and Engineering".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 27092

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Special Issue Editor

Dr. Weimin Li

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Guest Editor

Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA
Interests: cancer biology; tumor microenvironment; hydrogel; 3D culture; cell signaling

Special Issue Information

Dear Colleagues,

Biocompatible and biodegradable hydrogels fabricated from natural biomaterials have been widely used in biomedical research, bioengineering, drug delivery, and pharmaceutical applications. Biological hydrogels or composite hydrogels containing extracellular matrix (ECM) proteins, bioactive material, or peptides, such as collagen, fibronectin, laminin, hyaluronic acid, elastin, glycosaminoglycans, alginate, etc., have demonstrated great capabilities in advancing our understanding of cell biology in native tissue microenvironments, human physiological and pathological conditions. To further advance the field and provide a forum for scientific discussion on applications of biological hydrogel in cancer biology research, we welcome colleagues from various scientific fields to contribute research findings and review articles to this Special Issue for publication in Gels. The areas of interest include but are not limited to:

Compositional or/and structural properties of hydrogel related to cancer cell activities in hydrogel cultures;
Biological activities of cancer cells, such as growth, proliferation, differentiation, migration, invasion, transcription, translation, and molecular trafficking, regulated by hydrogels, hydrogel component(s), extracellular signals, or exogenous molecules;
Fabrication of biological hydrogel for cancer research;
Proteomics or metabolomics studies of molecular aspects of cancer cells biology in hydrogel;
DNA or RNA sequencing studies of gene expression and its regulation in hydrogel-based cancer cell culture models;
Immunological responses of cancer cells in biological hydrogel;
Hydrogel three-dimensional (3D) tissue culture studies of cancer cell biology;
Imaging studies of cancer cell biology in biological hydrogels;
Bioengineering using biological hydrogels for cancer cell biology studies;
Cancer cell animal models related to hydrogel applications;
Anticancer drug testing or delivery with biological hydrogel;
Computational analysis or modeling of biological hydrogel applications in cancer biology.

Dr. Weimin Li
Guest Editor

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Keywords

hydrogel
fabrication and characterization
structures and mechanics
composition
cancer cell biology
bioactivities
3D culture
-omics analysis
DNA/RNA sequencing
gene expression
imaging
bioengineering
drug delivery
computation
animal model

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Published Papers (10 papers)

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Research

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19 pages, 4062 KiB

Open AccessArticle

Nanoparticle Dynamics in Composite Hydrogels Exposed to Low-Frequency Focused Ultrasound

by Caroline Einen, Sebastian E. N. Price, Kim Ulvik, Magnus Aa. Gjennestad, Rune Hansen, Signe Kjelstrup and Catharina de Lange Davies

Gels 2023, 9(10), 771; https://doi.org/10.3390/gels9100771 - 22 Sep 2023

Cited by 1 | Viewed by 1535

Abstract

Pulsed focused ultrasound (FUS) in combination with microbubbles has been shown to improve delivery and penetration of nanoparticles in tumors. To understand the mechanisms behind this treatment, it is important to evaluate the contribution of FUS without microbubbles on increased nanoparticle penetration and transport in the tumor extracellular matrix (ECM). A composite agarose hydrogel was made to model the porous structure, the acoustic attenuation and the hydraulic conductivity of the tumor ECM. Single-particle tracking was used as a novel method to monitor nanoparticle dynamics in the hydrogel during FUS exposure. FUS exposure at 1 MHz and 1 MPa was performed to detect any increase in nanoparticle diffusion or particle streaming at acoustic parameters relevant for FUS in combination with microbubbles. Results were compared to a model of acoustic streaming. The nanoparticles displayed anomalous diffusion in the hydrogel, and FUS with a duty cycle of 20% increased the nanoparticle diffusion coefficient by 23%. No increase in diffusion was found for lower duty cycles. FUS displaced the hydrogel itself at duty cycles above 10%; however, acoustic streaming was found to be negligible. In conclusion, pulsed FUS alone cannot explain the enhanced penetration of nanoparticles seen when using FUS and microbubbles for nanoparticle delivery, but it could be used as a tool to enhance diffusion of particles in the tumor ECM. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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20 pages, 3723 KiB

Open AccessArticle

Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment

by Saud Almawash, Ahmed M. Mohammed, Mohamed A. El Hamd and Shaaban K. Osman

Gels 2023, 9(4), 326; https://doi.org/10.3390/gels9040326 - 12 Apr 2023

Cited by 3 | Viewed by 2031

Abstract

Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host β-cyclodextrin polymers (8armPEG20k-CD and pβ-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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12 pages, 4431 KiB

Open AccessArticle

Identification of the Collagen Types Essential for Mammalian Breast Acinar Structures

by Chandler R. Keller, Kelsey F. Ruud, Steve R. Martinez and Weimin Li

Gels 2022, 8(12), 837; https://doi.org/10.3390/gels8120837 - 18 Dec 2022

Cited by 3 | Viewed by 2730

Abstract

Modeling human breast tissue architecture is essential to study the pathophysiological conditions of the breast. We report that normal mammary epithelial cells grown in human breast extracellular matrix (ECM) hydrogel formed acini structurally similar to those of human and pig mammary tissues. Type I, II, III and V collagens were commonly identified in human, pig, and mouse breast ECM. Mammary epithelial cells formed acini on certain types or combinations of the four collagens at normal levels of breast tissue elasticity. Comparison of the collagen species in mouse normal breast and breast tumor ECM revealed common and distinct sets of collagens within the two types of tissues. Elevated expression of collagen type I alpha 1 chain (Col1a1) was found in mouse and human breast cancers. Collagen type XXV alpha 1 chain (Col25a1) was identified in mouse breast tumors but not in normal breast tissues. Our data provide strategies for modeling human breast pathophysiological structures and functions using native tissue-derived hydrogels and offer insight into the potential contributions of different collagen types in breast cancer development. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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14 pages, 7349 KiB

Open AccessArticle

Mechanisms of Basement Membrane Micro-Perforation during Cancer Cell Invasion into a 3D Collagen Gel

by Shayan S. Nazari, Andrew D. Doyle and Kenneth M. Yamada

Gels 2022, 8(9), 567; https://doi.org/10.3390/gels8090567 - 7 Sep 2022

Cited by 7 | Viewed by 3598

Abstract

Cancer invasion through basement membranes represents the initial step of tumor dissemination and metastasis. However, little is known about how human cancer cells breach basement membranes. Here, we used a three-dimensional in vitro invasion model consisting of cancer spheroids encapsulated by a basement membrane and embedded in 3D collagen gels to visualize the early events of cancer invasion by confocal microscopy and live-cell imaging. Human breast cancer cells generated large numbers of basement membrane perforations, or holes, of varying sizes that expanded over time during cell invasion. We used a wide variety of small molecule inhibitors to probe the mechanisms of basement membrane perforation and hole expansion. Protease inhibitor treatment (BB94), led to a 63% decrease in perforation size. After myosin II inhibition (blebbistatin), the basement membrane perforation area decreased by only 15%. These treatments produced correspondingly decreased cellular breaching events. Interestingly, inhibition of actin polymerization dramatically decreased basement membrane perforation by 80% and blocked invasion. Our findings suggest that human cancer cells can primarily use proteolysis and actin polymerization to perforate the BM and to expand perforations for basement membrane breaching with a relatively small contribution from myosin II contractility. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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14 pages, 3153 KiB

Open AccessArticle

Bioinspired Sandcastle Worm-Derived Peptide-Based Hybrid Hydrogel for Promoting the Formation of Liver Spheroids

by Yu-Hsu Chen, Yuan-Hao Ku, Kuo-Cheng Wang, Hung-Chi Chiang, Yu-Pao Hsu, Ming-Te Cheng, Ching-Shuen Wang and Yinshen Wee

Gels 2022, 8(3), 149; https://doi.org/10.3390/gels8030149 - 27 Feb 2022

Cited by 5 | Viewed by 3060

Abstract

The generation of hepatic spheroids is beneficial for a variety of potential applications, including drug development, disease modeling, transplantation, and regenerative medicine. Natural hydrogels are obtained from tissues and have been widely used to promote the growth, differentiation, and retention of specific functionalities of hepatocytes. However, relying on natural hydrogels for the generation of hepatic spheroids, which have batch to batch variations, may in turn limit the previously mentioned potential applications. For this reason, we researched a way to establish a three-dimensional (3D) culture system that more closely mimics the interaction between hepatocytes and their surrounding microenvironments, thereby potentially offering a more promising and suitable system for drug development, disease modeling, transplantation, and regenerative medicine. Here, we developed self-assembling and bioactive hybrid hydrogels to support the generation and growth of hepatic spheroids. Our hybrid hydrogels (PC4/Cultrex) inspired by the sandcastle worm, an Arg-Gly-Asp (RGD) cell adhesion sequence, and bioactive molecules derived from Cultrex BME (Basement Membrane Extract). By performing optimizations to the design, the PC4/Cultrex hybrid hydrogels can enhance HepG2 cells to form spheroids and express their molecular signatures (e.g., Cyp3A4, Cyp7a1, A1at, Afp, Ck7, Ck1, and E-cad). Our study demonstrated that this hybrid hydrogel system offers potential advantages for hepatocytes in proliferating, differentiating, and self-organizing to form hepatic spheroids in a more controllable and reproducible manner. In addition, it is a versatile and cost-effective method for 3D tissue cultures in mass quantities. Importantly, we demonstrate that it is feasible to adapt a bioinspired approach to design biomaterials for 3D culture systems, which accelerates the design of novel peptide structures and broadens our research choices on peptide-based hydrogels. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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19 pages, 8942 KiB

Open AccessArticle

Curcuminoid Co-Loading Platinum Heparin-Poloxamer P403 Nanogel Increasing Effectiveness in Antitumor Activity

by Ngoc The Nguyen, Quynh Anh Bui, Hoang Huong Nhu Nguyen, Tien Thanh Nguyen, Khanh Linh Ly, Ha Le Bao Tran, Vu Nguyen Doan, Tran Thi Yen Nhi, Ngoc Hoa Nguyen, Ngoc Hao Nguyen, Ngoc Quyen Tran and Dinh Trung Nguyen

Gels 2022, 8(1), 59; https://doi.org/10.3390/gels8010059 - 14 Jan 2022

Cited by 20 | Viewed by 3786

Abstract

Nanosized multi-drug delivery systems provide synergistic effects between drugs and bioactive compounds, resulting in increased overall efficiency and restricted side effects compared to conventional single-drug chemotherapy. In this study, we develop an amphiphilic heparin-poloxamer P403 (HP403) nanogel that could effectively co-load curcuminoid (Cur) and cisplatin hydrate (CisOH) (HP403@CisOH@Cur) via two loading mechanisms. The HP403 nanogels and HP403@CisOH@Cur nanogels were closely analyzed with ¹H-NMR spectroscopy, FT-IR spectroscopy, TEM, and DLS, exhibiting high stability in spherical forms. In drug release profiles, accelerated behavior of Cur and CisOH at pH 5.5 compared with neutral pH was observed, suggesting effective delivery of the compounds in tumor sites. In vitro studies showed high antitumor activity of HP403@CisOH@Cur nanogels, while in vivo assays showed that the dual-drug platform prolonged the survival time of mice and prevented tail necrosis. In summary, HP403@CisOH@Cur offers an intriguing strategy to achieve the cisplatin and curcumin synergistic effect in a well-designed delivery platform that increases antitumor effectiveness and overcomes undesired consequences caused by cisplatin in breast cancer treatment. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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13 pages, 2173 KiB

Open AccessArticle

Stimuli-Responsive Dual Cross-Linked N-Carboxyethylchitosan Hydrogels with Tunable Dissolution Rate

by Svetlana Bratskaya, Anna Skatova, Yuliya Privar, Andrey Boroda, Ekaterina Kantemirova, Mariya Maiorova and Alexander Pestov

Gels 2021, 7(4), 188; https://doi.org/10.3390/gels7040188 - 29 Oct 2021

Cited by 18 | Viewed by 2095

Abstract

Here, we discuss the applicability of (methylenebis(salicylaldehyde)—MbSA) for the fabrication of the stimuli-responsive N-carboxyethylchitosan (CEC) hydrogels with a tunable dissolution rate under physiological conditions. In comparison with non-covalent salicylimine hydrogels, MbSA cross-linking via covalent bis(‘imine clip’) and non-covalent hydrophobic interactions allowed the fabrication of hydrogels with storage moduli > 1 kPa at ten-fold lower aldehyde/CEC molar ratio with the preservation of pH- and amino-acid responsive behavior. Although MbSA-cross-linked CEC hydrogels were stable at neutral and weakly alkaline pH, their disassembly in cell growth medium (Dulbecco’s modified Eagle’s medium, DMEM) under physiological conditions was feasible due to transimination reaction with amino acids contained in DMEM. Depending on the cross-linking density, the complete dissolution time of the fabricated hydrogels varied from 28 h to 11 days. The cytotoxicity of MbSA cross-linked CEC hydrogels toward a human colon carcinoma cell line (HCT 116) and primary human dermal fibroblasts (HDF) was remarkably lower in comparison with CEC-salicylimine hydrogels. Fast gelation, relatively low cytotoxicity, and tunable stimuli-induced disassembly under physiological conditions make MbSA cross-linked CEC hydrogels promising for drug encapsulation and release, 3D printing, cell culturing, and other biomedical applications. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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Review

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26 pages, 1145 KiB

Open AccessReview

Biomimetic Hydrogel Strategies for Cancer Therapy

by Awatef M. Alshehri and Otto C. Wilson, Jr.

Gels 2024, 10(7), 437; https://doi.org/10.3390/gels10070437 - 30 Jun 2024

Cited by 1 | Viewed by 1514

Abstract

Recent developments in biomimetic hydrogel research have expanded the scope of biomedical technologies that can be used to model, diagnose, and treat a wide range of medical conditions. Cancer presents one of the most intractable challenges in this arena due to the surreptitious mechanisms that it employs to evade detection and treatment. In order to address these challenges, biomimetic design principles can be adapted to beat cancer at its own game. Biomimetic design strategies are inspired by natural biological systems and offer promising opportunities for developing life-changing methods to model, detect, diagnose, treat, and cure various types of static and metastatic cancers. In particular, focusing on the cellular and subcellular phenomena that serve as fundamental drivers for the peculiar behavioral traits of cancer can provide rich insights into eradicating cancer in all of its manifestations. This review highlights promising developments in biomimetic nanocomposite hydrogels that contribute to cancer therapies via enhanced drug delivery strategies and modeling cancer mechanobiology phenomena in relation to metastasis and synergistic sensing systems. Creative efforts to amplify biomimetic design research to advance the development of more effective cancer therapies will be discussed in alignment with international collaborative goals to cure cancer. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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27 pages, 3757 KiB

Open AccessReview

3D Bioprinting as a Powerful Technique for Recreating the Tumor Microenvironment

by Ilaria Parodi, Donatella Di Lisa, Laura Pastorino, Silvia Scaglione and Marco Massimo Fato

Gels 2023, 9(6), 482; https://doi.org/10.3390/gels9060482 - 12 Jun 2023

Cited by 13 | Viewed by 3206

Abstract

In vitro three-dimensional models aim to reduce and replace animal testing and establish new tools for oncology research and the development and testing of new anticancer therapies. Among the various techniques to produce more complex and realistic cancer models is bioprinting, which allows the realization of spatially controlled hydrogel-based scaffolds, easily incorporating different types of cells in order to recreate the crosstalk between cancer and stromal components. Bioprinting exhibits other advantages, such as the production of large constructs, the repeatability and high resolution of the process, as well as the possibility of vascularization of the models through different approaches. Moreover, bioprinting allows the incorporation of multiple biomaterials and the creation of gradient structures to mimic the heterogeneity of the tumor microenvironment. The aim of this review is to report the main strategies and biomaterials used in cancer bioprinting. Moreover, the review discusses several bioprinted models of the most diffused and/or malignant tumors, highlighting the importance of this technique in establishing reliable biomimetic tissues aimed at improving disease biology understanding and high-throughput drug screening. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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27 pages, 7323 KiB

Open AccessReview

Engineering Hydrogels for Modulation of Dendritic Cell Function

by Cuifang Wu, Lijing Teng, Caiyuan Wang, Tianbao Qian, Zuquan Hu and Zhu Zeng

Gels 2023, 9(2), 116; https://doi.org/10.3390/gels9020116 - 1 Feb 2023

Cited by 6 | Viewed by 2254

Abstract

Dendritic cells (DCs), the most potent antigen-presenting cells, are necessary for the effective activation of naïve T cells. DCs encounter numerous microenvironments with different biophysical properties, such as stiffness and viscoelasticity. Considering the emerging importance of mechanical cues for DC function, it is essential to understand the impacts of these cues on DC function in a physiological or pathological context. Engineered hydrogels have gained interest for the exploration of the impacts of biophysical matrix cues on DC functions, owing to their extracellular-matrix-mimetic properties, such as high water content, a sponge-like pore structure, and tunable mechanical properties. In this review, the introduction of gelation mechanisms of hydrogels is first summarized. Then, recent advances in the substantial effects of developing hydrogels on DC function are highlighted, and the potential molecular mechanisms are subsequently discussed. Finally, persisting questions and future perspectives are presented. Full article

(This article belongs to the Special Issue Cancer Cell Biology in Biological Hydrogel)

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