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Cell-Biomaterial Interaction 2021

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 35197

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Special Issue Editors

Dr. Silvia Panseri

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Guest Editor

National Research Council, Institute of Science and Technology for Ceramics, Roma, Italy
Interests: tissue engineering; nanomedicine; cell–material interaction; 3D biomaterials; cell therapy; cell biology; magnetic nanoparticles
Special Issues, Collections and Topics in MDPI journals

Dr. Monica Montesi

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Guest Editor

National Research Council of Italy Institute of Science and Technology for Ceramics (ISTEC-CNR), Via Granarolo 64, I-48018 Faenza, Italy
Interests: cellular and molecular biology; material science; nanotechnology; tissue engineering and regenerative medicine; 2D and 3D cellular models; cell/biomaterial interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There is a growing interest in generating artificial tissues as biological substitutes in regenerative medicine applications and nanomedicine. Efforts have been made to design advanced biofunctional systems by combining cells (e.g., stem cells, differentiated cells, induced pluripotent stem cells) and biomaterials. It is well known that cells recognize and interact with biomaterials in different forms (e.g., nanoparticles, 3D scaffold, coating, film) through a plethora of plasma membrane proteins that activate a signal cascade, steering cells toward a selected behavior. Therefore, developing innovative biomaterials with peculiar physicochemical properties, focusing on specific architectures/porosity, is instrumental to tuning cell fate. Moreover, a specific biodecoration of a material with biomolecules/drugs could further enhance the bioactivity of a material itself, contributing to improved cellular response.

This Special Issue on “Cell–Material Interactions 2021” focuses on several aspects of cell/biomaterial interaction. Herein, we invite contributions of reviews and/or original papers reporting recent efforts in the field of biomaterial applications.

Dr. Silvia Panseri
Dr. Monica Montesi
Guest Editors

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Keywords

Cell-material interaction
Biomaterials
Regenerative medicine
Stem cells
Cell therapy
Nanomedicine
Regenerative medicine
Cell fate
Nanoparticles
3D scaffold
Biofunctionalization

Published Papers (14 papers)

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16 pages, 6799 KiB

Open AccessArticle

Mammalian Cell Interaction with Periodic Surface Nanostructures

by Petr Slepička, Silvie Rimpelová, Vladimíra Svobodová Pavlíčková, Nikola Slepičková Kasálková, Klaudia Hurtuková, Dominik Fajstavr and Václav Švorčík

Int. J. Mol. Sci. 2022, 23(9), 4676; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094676 - 23 Apr 2022

Cited by 1 | Viewed by 1608

Abstract

Here, we report on the nanopatterning of different aromatic polymer substrates achieved by KrF excimer laser treatment. The conditions for the construction of the laser-induced periodic surface structures, the so-called LIPSS pattern, were established by optimized laser fluence and a number of pulses. The polymer substrates were polyethylene naphthalate (PEN), polyethersulfone (PES), and polystyrene (PS), which were chosen since they are thermally, chemically, and mechanically resistant polymers with high absorption coefficients at the excimer laser wavelength. The surface morphology of the treated substrates was investigated by atomic force microscopy and scanning electron microscopy, and the roughness and effective surface area on the modified samples were determined. Elemental concentration was characterized by energy-dispersive (EDX) analysis, surface chemistry was determined with X-ray photoelectron spectroscopy (XPS). The samples with the formation of LIPSS induced by 10 mJ·cm⁻² with 1000, 3000, and 6000 pulses were used for subsequent in vitro cytocompatibility tests using human cells from osteosarcoma (U-2 OS). The LIPSS pattern and its ability of significant cell guidance were confirmed for some of the studied samples. Cell morphology, adhesion, and proliferation were evaluated. The results strongly contribute to the development of novel applications using nanopatterned polymers, e.g., in tissue engineering, cell analysis or in combination with metallization for sensor construction. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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12 pages, 951 KiB

Open AccessArticle

Controlled Liposome Delivery from Chitosan-Based Thermosensitive Hydrogel for Regenerative Medicine

by Franco Furlani, Arianna Rossi, Maria Aurora Grimaudo, Giada Bassi, Elena Giusto, Filippo Molinari, Florigio Lista, Monica Montesi and Silvia Panseri

Int. J. Mol. Sci. 2022, 23(2), 894; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020894 - 14 Jan 2022

Cited by 24 | Viewed by 3242

Abstract

This work describes the development of an injectable nanocomposite system based on a chitosan thermosensitive hydrogel combined with liposomes for regenerative medicine applications. Liposomes with good physicochemical properties are prepared and embedded within the chitosan network. The resulting nanocomposite hydrogel is able to provide a controlled release of the content from liposomes, which are able to interact with cells and be internalized. The cellular uptake is enhanced by the presence of a chitosan coating, and cells incubated with liposomes embedded within thermosensitive hydrogels displayed a higher cell uptake compared to cells incubated with liposomes alone. Furthermore, the gelation temperature of the system resulted to be equal to 32.6 °C; thus, the system can be easily injected in the target site to form a hydrogel at physiological temperature. Given the peculiar performance of the selected systems, the resulting thermosensitive hydrogels are a versatile platform and display potential applications as controlled delivery systems of liposomes for tissue regeneration. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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17 pages, 3631 KiB

Open AccessArticle

Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells

by Lysann M. Kroschwald, Felix Allerdt, Anne Bernhardt, Sandra Rother, Kai Zheng, Iram Maqsood, Norbert Halfter, Christiane Heinemann, Stephanie Möller, Matthias Schnabelrauch, Michael C. Hacker, Stefan Rammelt, Aldo R. Boccaccini and Vera Hintze

Int. J. Mol. Sci. 2021, 22(23), 12819; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312819 - 26 Nov 2021

Cited by 8 | Viewed by 1930

Abstract

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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12 pages, 1897 KiB

Open AccessArticle

Hierarchically Structured Polystyrene-Based Surfaces Amplifying Fluorescence Signals: Cytocompatibility with Human Induced Pluripotent Stem Cell

by Kateřina Skopalová, Katarzyna Anna Radaszkiewicz, Markéta Kadlečková, Jiří Pacherník, Antonín Minařík, Zdenka Capáková, Věra Kašpárková, Aleš Mráček, Eliška Daďová and Petr Humpolíček

Int. J. Mol. Sci. 2021, 22(21), 11943; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111943 - 04 Nov 2021

Cited by 3 | Viewed by 1828

Abstract

An innovative multi-step phase separation process was used to prepare tissue culture for the polystyrene-based, hierarchically structured substrates, which mimicked in vivo microenvironment and architecture. Macro- (pore area from 3000 to 18,000 µm²; roughness (Ra) 7.2 ± 0.1 µm) and meso- (pore area from 50 to 300 µm²; Ra 1.1 ± 0.1 µm) structured substrates covered with micro-pores (area around 3 µm²) were prepared and characterised. Both types of substrate were suitable for human-induced pluripotent stem cell (hiPSC) cultivation and were found to be beneficial for the induction of cardiomyogenesis in hiPSC. This was confirmed both by the number of promoted proliferated cells and the expressions of specific markers (Nkx2.5, MYH6, MYL2, and MYL7). Moreover, the substrates amplified the fluorescence signal when Ca²⁺ flow was monitored. This property, together with cytocompatibility, make this material especially suitable for in vitro studies of cell/material interactions within tissue-mimicking environments. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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18 pages, 2086 KiB

Open AccessArticle

Cerium Oxide Nanoparticles Alleviate Hepatic Fibrosis Phenotypes In Vitro

by Adrian Boey, Shu Qing Leong, Sayali Bhave and Han Kiat Ho

Int. J. Mol. Sci. 2021, 22(21), 11777; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111777 - 29 Oct 2021

Cited by 13 | Viewed by 2532

Abstract

Exposure to metallic nanoparticles (NPs) can result in inadvertent NP accumulation in body tissues. While their subsequent cellular interactions can lead to unintended consequences and are generally regarded as detrimental for health, they can on occasion mediate biologically beneficial effects. Among NPs, cerium oxide nanoparticles (CeO₂ NP) possess strong antioxidant properties and have shown to alleviate certain pathological conditions. Herein, we show that the presence of cubic 25 nm CeO₂ NP was able to reduce TGF-β-mediated activation in the cultured hepatic stellate cell line LX2 by reducing oxidative stress levels and TGF-β-mediated signalling. These cells displayed reduced classical liver fibrosis phenotypes, such as diminished fibrogenesis, altered matrix degradation, decreased cell motility, modified contractability and potentially lowered autophagy. These findings demonstrate that CeO₂ NP may be able to ameliorate hepatic fibrosis and suggest a possible therapeutic pathway for an otherwise difficult-to-treat condition. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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11 pages, 3957 KiB

Open AccessArticle

Supercritical Carbon Dioxide Treatment of Porous Silicon Increases Biocompatibility with Cardiomyocytes

by David Jui-Yang Feng, Hung-Yin Lin, James L. Thomas, Hsing-Yu Wang, Chien-Yu Lin, Chen-Yuan Chen, Kai-Hsi Liu and Mei-Hwa Lee

Int. J. Mol. Sci. 2021, 22(19), 10709; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910709 - 02 Oct 2021

Cited by 1 | Viewed by 1474

Abstract

Porous silicon is of current interest for cardiac tissue engineering applications. While porous silicon is considered to be a biocompatible material, it is important to assess whether post-etching surface treatments can further improve biocompatibility and perhaps modify cellular behavior in desirable ways. In this work, porous silicon was formed by electrochemically etching with hydrofluoric acid, and was then treated with oxygen plasma or supercritical carbon dioxide (scCO₂). These processes yielded porous silicon with a thickness of around 4 μm. The different post-etch treatments gave surfaces that differed greatly in hydrophilicity: oxygen plasma-treated porous silicon had a highly hydrophilic surface, while scCO₂ gave a more hydrophobic surface. The viabilities of H9c2 cardiomyocytes grown on etched surfaces with and without these two post-etch treatments was examined; viability was found to be highest on porous silicon treated with scCO₂. Most significantly, the expression of some key genes in the angiogenesis pathway was strongly elevated in cells grown on the scCO₂-treated porous silicon, compared to cells grown on the untreated or plasma-treated porous silicon. In addition, the expression of several apoptosis genes were suppressed, relative to the untreated or plasma-treated surfaces. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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17 pages, 2048 KiB

Open AccessArticle

Integrin β1 Promotes Pancreatic Tumor Growth by Upregulating Kindlin-2 and TGF-β Receptor-2

by Md Saimon Mia, Yagna Jarajapu, Reena Rao and Sijo Mathew

Int. J. Mol. Sci. 2021, 22(19), 10599; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910599 - 30 Sep 2021

Cited by 8 | Viewed by 2333

Abstract

The tumor microenvironment plays a critical role in defining the growth and malignancy of solid tumors. Extracellular matrix (ECM) proteins such as collagen, vitronectin, and fibronectin are major components of the tumor microenvironment. Tumor growth-promoting reciprocal interaction between ECM and cytoplasmic proteins is regulated by the cell surface receptors called integrins. This study investigated the mechanism by which integrin β1 promotes pancreatic tumor growth. In MIA PaCa-2 pancreatic cancer cell line, the loss of integrin β1 protein reduced the ability of cells to proliferate in a 3D matrix and compromised the ability to form a focal adhesion complex. Decreased expression of integrin α5 was observed in KO cells, which resulted in impaired cell spreading and adhesion on vitronectin and fibronectin. Reduced expression of the integrin-associated protein, kindlin-2 was also recorded. The downregulation of kindlin-2 decreased the phosphorylation of Smad2/3 by reducing the expression of TGF-β receptor 2. These results unravel a new mechanism of integrin β1 in tumor growth by modifying the expression of kindlin-2 and TGF-β receptor 2 signaling. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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15 pages, 4697 KiB

Open AccessArticle

Influence of Human Jaw Periosteal Cells Seeded β-Tricalcium Phosphate Scaffolds on Blood Coagulation

by Marbod Weber, Felix Umrath, Heidrun Steinle, Lukas-Frank Schmitt, Lin Tzu Yu, Christian Schlensak, Hans-Peter Wendel, Siegmar Reinert, Dorothea Alexander and Meltem Avci-Adali

Int. J. Mol. Sci. 2021, 22(18), 9942; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22189942 - 14 Sep 2021

Cited by 4 | Viewed by 1728

Abstract

Tissue engineering offers auspicious opportunities in oral and maxillofacial surgery to heal bone defects. For this purpose, the combination of cells with stability-providing scaffolds is required. Jaw periosteal cells (JPCs) are well suited for regenerative therapies, as they are easily accessible and show strong osteogenic potential. In this study, we analyzed the influence of uncoated and polylactic-co-glycolic acid (PLGA)-coated β-tricalcium phosphate (β-TCP) scaffolds on JPC colonization and subsequent osteogenic differentiation. Furthermore, interaction with the human blood was investigated. This study demonstrated that PLGA-coated and uncoated β-TCP scaffolds can be colonized with JPCs and further differentiated into osteogenic cells. On day 15, after cell seeding, JPCs with and without osteogenic differentiation were incubated with fresh human whole blood under dynamic conditions. The activation of coagulation, complement system, inflammation, and blood cells were analyzed using ELISA and scanning electron microscopy (SEM). JPC-seeded scaffolds showed a dense cell layer and osteogenic differentiation capacity on both PLGA-coated and uncoated β-TCP scaffolds. SEM analyses showed no relevant blood cell attachment and ELISA results revealed no significant increase in most of the analyzed cell activation markers (β-thromboglobulin, Sc5B-9, polymorphonuclear (PMN)-elastase). However, a notable increase in thrombin-antithrombin III (TAT) complex levels, as well as fibrin fiber accumulation on JPC-seeded β-TCP scaffolds, was detected compared to the scaffolds without JPCs. Thus, this study demonstrated that besides the scaffold material the cells colonizing the scaffolds can also influence hemostasis, which can influence the regeneration of bone tissue. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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16 pages, 2870 KiB

Open AccessArticle

Therapeutic Strategies for IVD Regeneration through Hyaluronan/SDF-1-Based Hydrogel and Intravenous Administration of MSCs

by Carla Cunha, Catarina Leite Pereira, Joana R. Ferreira, Cláudia Ribeiro-Machado, Sibylle Grad, Susana G. Santos and Raquel M. Gonçalves

Int. J. Mol. Sci. 2021, 22(17), 9609; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179609 - 04 Sep 2021

Cited by 7 | Viewed by 2637

Abstract

Intervertebral disc (IVD) degeneration involves a complex cascade of events, including degradation of the native extracellular matrix, loss of water content, and decreased cell numbers. Cell recruitment strategies for the IVD have been increasingly explored, aiming to recruit either endogenous or transplanted cells. This study evaluates the IVD therapeutic potential of a chemoattractant delivery system (HAPSDF5) that combines a hyaluronan-based thermoreversible hydrogel (HAP) and the chemokine stromal cell derived factor-1 (SDF-1). HAPSDF5 was injected into the IVD and was combined with an intravenous injection of mesenchymal stem/stromal cells (MSCs) in a pre-clinical in vivo IVD lesion model. The local and systemic effects were evaluated two weeks after treatment. The hydrogel by itself (HAP) did not elicit any adverse effect, showing potential to be administrated by intradiscal injection. HAPSDF5 induced higher cell numbers, but no evidence of IVD regeneration was observed. MSCs systemic injection seemed to exert a role in IVD regeneration to some extent through a paracrine effect, but no synergies were observed when HAPSDF5 was combined with MSCs. Overall, this study shows that although the injection of chemoattractant hydrogels and MSC recruitment are feasible approaches for IVD, IVD regeneration using this strategy needs to be further explored before successful clinical translation. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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12 pages, 4062 KiB

Open AccessArticle

Porous Biphasic Calcium Phosphate Granules from Oyster Shell Promote the Differentiation of Induced Pluripotent Stem Cells

by Wen-Fu Ho, Mei-Hwa Lee, James L. Thomas, Jin-An Li, Shih-Ching Wu, Hsueh-Chuan Hsu and Hung-Yin Lin

Int. J. Mol. Sci. 2021, 22(17), 9444; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179444 - 31 Aug 2021

Cited by 9 | Viewed by 1991

Abstract

Oyster shells are rich in calcium, and thus, the potential use of waste shells is in the production of calcium phosphate (CaP) minerals for osteopathic biomedical applications, such as scaffolds for bone regeneration. Implanted scaffolds should stimulate the differentiation of induced pluripotent stem cells (iPSCs) into osteoblasts. In this study, oyster shells were used to produce nano-grade hydroxyapatite (HA) powder by the liquid-phase precipitation. Then, biphasic CaP (BCP) bioceramics with two different phase ratios were obtained by the foaming of HA nanopowders and sintering by two different two-stage heat treatment processes. The different sintering conditions yielded differences in structure and morphology of the BCPs, as determined by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Brunauer–Emmett–Teller (BET) surface area analysis. We then set out to determine which of these materials were most biocompatible, by co-culturing with iPSCs and examining the gene expression in molecular pathways involved in self-renewal and differentiation of iPSCs. We found that sintering for a shorter time at higher temperatures gave higher expression levels of markers for proliferation and (early) differentiation of the osteoblast. The differences in biocompatibility may be related to a more hierarchical pore structure (micropores within macropores) obtained with briefer, high-temperature sintering. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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13 pages, 2776 KiB

Open AccessArticle

A DNA Aptameric Ligand of Human Transferrin Receptor Generated by Cell-SELEX

by Nan Zhang, Tao Bing, Luyao Shen, Le Feng, Xiangjun Liu and Dihua Shangguan

Int. J. Mol. Sci. 2021, 22(16), 8923; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168923 - 19 Aug 2021

Cited by 13 | Viewed by 2829

Abstract

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR). As a man-made ligand of TfR, aptamer HG1-9 was demonstrated to bind at the same site of human TfR as transferrin with comparable binding affinity, and was proved to cross the epithelium barrier through transferrin receptor-mediated transcytosis. These results suggest that aptamer HG1-9 holds potential as a promising ligand to develop general cancer-targeted diagnostics and therapeutics. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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21 pages, 6332 KiB

Open AccessArticle

Laser Direct Writing via Two-Photon Polymerization of 3D Hierarchical Structures with Cells-Antiadhesive Properties

by Irina A. Paun, Bogdan S. Calin, Cosmin C. Mustaciosu, Eugenia Tanasa, Antoniu Moldovan, Agata Niemczyk and Maria Dinescu

Int. J. Mol. Sci. 2021, 22(11), 5653; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115653 - 26 May 2021

Cited by 5 | Viewed by 2189

Abstract

We report the design and fabrication by laser direct writing via two photons polymerization of innovative hierarchical structures with cell-repellency capability. The structures were designed in the shape of “mushrooms”, consisting of an underside (mushroom’s leg) acting as a support structure and a top side (mushroom’s hat) decorated with micro- and nanostructures. A ripple-like pattern was created on top of the mushrooms, over length scales ranging from several µm (microstructured mushroom-like pillars, MMP) to tens of nm (nanostructured mushroom-like pillars, NMP). The MMP and NMP structures were hydrophobic, with contact angles of (127 ± 2)° and (128 ± 4)°, respectively, whereas flat polymer surfaces were hydrophilic, with a contact angle of (43 ± 1)°. The cell attachment on NMP structures was reduced by 55% as compared to the controls, whereas for the MMP, a reduction of only 21% was observed. Moreover, the MMP structures preserved the native spindle-like with phyllopodia cellular shape, whereas the cells from NMP structures showed a round shape and absence of phyllopodia. Overall, the NMP structures were more effective in impeding the cellular attachment and affected the cell shape to a greater extent than the MMP structures. The influence of the wettability on cell adhesion and shape was less important, the cellular behavior being mainly governed by structures’ topography. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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Review

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19 pages, 1093 KiB

Open AccessReview

Predicting the In Vivo Performance of Cardiovascular Biomaterials: Current Approaches In Vitro Evaluation of Blood-Biomaterial Interactions

by Anne Strohbach and Raila Busch

Int. J. Mol. Sci. 2021, 22(21), 11390; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111390 - 21 Oct 2021

Cited by 9 | Viewed by 3944

Abstract

The therapeutic efficacy of a cardiovascular device after implantation is highly dependent on the host-initiated complement and coagulation cascade. Both can eventually trigger thrombosis and inflammation. Therefore, understanding these initial responses of the body is of great importance for newly developed biomaterials. Subtle modulation of the associated biological processes could optimize clinical outcomes. However, our failure to produce truly blood compatible materials may reflect our inability to properly understand the mechanisms of thrombosis and inflammation associated with biomaterials. In vitro models mimicking these processes provide valuable insights into the mechanisms of biomaterial-induced complement activation and coagulation. Here, we review (i) the influence of biomaterials on complement and coagulation cascades, (ii) the significance of complement-coagulation interactions for the clinical success of cardiovascular implants, (iii) the modulation of complement activation by surface modifications, and (iv) in vitro testing strategies. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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22 pages, 1522 KiB

Open AccessReview

Mechanical Studies of the Third Dimension in Cancer: From 2D to 3D Model

by Francesca Paradiso, Stefano Serpelloni, Lewis W. Francis and Francesca Taraballi

Int. J. Mol. Sci. 2021, 22(18), 10098; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221810098 - 18 Sep 2021

Cited by 21 | Viewed by 3695

Abstract

From the development of self-aggregating, scaffold-free multicellular spheroids to the inclusion of scaffold systems, 3D models have progressively increased in complexity to better mimic native tissues. The inclusion of a third dimension in cancer models allows researchers to zoom out from a significant but limited cancer cell research approach to a wider investigation of the tumor microenvironment. This model can include multiple cell types and many elements from the extracellular matrix (ECM), which provides mechanical support for the tissue, mediates cell-microenvironment interactions, and plays a key role in cancer cell invasion. Both biochemical and biophysical signals from the extracellular space strongly influence cell fate, the epigenetic landscape, and gene expression. Specifically, a detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, is lacking. In this review, we focus on the latest achievements in the study of ECM biomechanics and mechanosensing in cancer on 3D scaffold-based and scaffold-free models, focusing on each platform’s level of complexity, up-to-date mechanical tests performed, limitations, and potential for further improvements. Full article

(This article belongs to the Special Issue Cell-Biomaterial Interaction 2021)

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