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Interactions of Cells with Biomaterials for Regenerative Medicine 3.0

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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 March 2023) | Viewed by 27428

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Prof. Dr. Agata Przekora

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Independent Unit of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, 20-093 Lublin, Poland
Interests: biomaterials; bioceramics; biopolymers; tissue engineering; bone scaffolds; wound dressings; skin substitutes; stem cells; cell culture models; cell-biomaterial interactions
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Dear Colleagues,

The biomaterials used for regenerative medicine applications should be non-toxic and biocompatible. Biocompatibility has a very broad meaning, including the non-toxicity of the materials; their ability to support cell adhesion, proliferation, and differentiation; as well as their non-immunogenic properties. Therefore, the evaluation of major cell–biomaterial interactions is a key factor in determining the biocompatibility and clinical usefulness of new biomaterials. It is important to know that in vitro tests can effectively replace animal models in the preliminary evaluation of: 1) cytotoxicity; 2) cell adhesion, spreading, and proliferation on a biomaterial; 3) cell differentiation; and 4) immune response to a biomaterial. Despite the possibility of the use of in vitro cellular models for the evaluation of materials’ biocompatibility, researchers still preferentially choose in vivo animal tests for this purpose. Nevertheless, the use of animal models at a preliminary stage or for comparative purposes is against the principles of the ‘3Rs’, aiming to replace, reduce, and refine the use of animals wherever possible.

The main goal of this Special Issue is to highlight the recent progress made in molecular biology and biotechnological techniques that allow a better exploitation of the potential of in vitro cellular models for the biocompatibility testing of novel biomaterials, suggesting molecular mechanisms of cell adhesion, proliferation, and biomaterial-induced activation of immune cells. All papers (reviews and original research articles) dealing with the in vitro and ex vivo determination of cell–biomaterial interactions are welcome. Manuscripts presenting interactions of biomaterials with prokaryotic cells (e.g., antibiofilm or the antibacterial activity of a material) are also encouraged; however, some description of at least basic cytotoxicity tests with eukaryotic cells should be included.

Dr. Agata Przekora
Guest Editor

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Keywords

ex vivo tissue explant models
in vitro cellular models
cell adhesion and spreading on the biomaterial
cell proliferation and differentiation on the biomaterial
immune response to biomaterial
biomaterial interactions with mesenchymal stem cells
biomaterial-induced macrophage polarization and cytokine release
bacteria adhesion and biofilm formation on the biomaterials

Related Special Issues

Interactions of Cells with Biomaterials for Regenerative Medicine 2.0 in International Journal of Molecular Sciences (11 articles)
Interactions of Cells with Biomaterials for Regenerative Medicine 4.0 in International Journal of Molecular Sciences (2 articles)

Published Papers (9 papers)

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Research

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29 pages, 7697 KiB

Open AccessArticle

Adipose-Derived Stem Cells in Reinforced Collagen Gel: A Comparison between Two Approaches to Differentiation towards Smooth Muscle Cells

by Elena Filova, Monika Supova, Adam Eckhardt, Marek Vrbacky, Andreu Blanquer, Martina Travnickova, Jarmila Knitlova, Tomas Suchy, Sarka Ryglova, Martin Braun, Zuzana Burdikova, Martin Schätz, Vera Jencova, Maxim Lisnenko, Lubos Behalek, Renata Prochazkova, Radek Sedlacek, Kristyna Kubasova and Lucie Bacakova

Int. J. Mol. Sci. 2023, 24(6), 5692; https://doi.org/10.3390/ijms24065692 - 16 Mar 2023

Viewed by 2749

Abstract

Scaffolds made of degradable polymers, such as collagen, polyesters or polysaccharides, are promising matrices for fabrication of bioartificial vascular grafts or patches. In this study, collagen isolated from porcine skin was processed into a gel, reinforced with collagen particles and with incorporated adipose tissue-derived stem cells (ASCs). The cell-material constructs were then incubated in a DMEM medium with 2% of FS (DMEM_part), with added polyvinylalcohol nanofibers (PVA_part sample), and for ASCs differentiation towards smooth muscle cells (SMCs), the medium was supplemented either with human platelet lysate released from PVA nanofibers (PVA_PL_part) or with TGF-β1 + BMP-4 (TGF + BMP_part). The constructs were further endothelialised with human umbilical vein endothelial cells (ECs). The immunofluorescence staining of alpha-actin and calponin, and von Willebrand factor, was performed. The proteins involved in cell differentiation, the extracellular matrix (ECM) proteins, and ECM remodelling proteins were evaluated by mass spectrometry on day 12 of culture. Mechanical properties of the gels with ASCs were measured via an unconfined compression test on day 5. Gels evinced limited planar shrinkage, but it was higher in endothelialised TGF + BMP_part gel. Both PVA_PL_part samples and TGF + BMP_part samples supported ASC growth and differentiation towards SMCs, but only PVA_PL_part supported homogeneous endothelialisation. Young modulus of elasticity increased in all samples compared to day 0, and PVA_PL_part gel evinced a slightly higher ratio of elastic energy. The results suggest that PVA_PL_part collagen construct has the highest potential to remodel into a functional vascular wall. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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18 pages, 5397 KiB

Open AccessArticle

Hydroxyapatite or Fluorapatite—Which Bioceramic Is Better as a Base for the Production of Bone Scaffold?—A Comprehensive Comparative Study

by Paulina Kazimierczak, Joanna Wessely-Szponder, Krzysztof Palka, Adriana Barylyak, Viktor Zinchenko and Agata Przekora

Int. J. Mol. Sci. 2023, 24(6), 5576; https://doi.org/10.3390/ijms24065576 - 14 Mar 2023

Cited by 9 | Viewed by 2458

Abstract

Hydroxyapatite (HAP) is the most common calcium phosphate ceramic that is used in biomedical applications, e.g., as an inorganic component of bone scaffolds. Nevertheless, fluorapatite (FAP) has gained great attention in the area of bone tissue engineering in recent times. The aim of this study was a comprehensive comparative evaluation of the biomedical potential of fabricated HAP- and FAP-based bone scaffolds, to assess which bioceramic is better for regenerative medicine applications. It was demonstrated that both biomaterials had a macroporous microstructure, with interconnected porosity, and were prone to slow and gradual degradation in a physiological environment and in acidified conditions mimicking the osteoclast-mediated bone resorption process. Surprisingly, FAP-based biomaterial revealed a significantly higher degree of biodegradation than biomaterial containing HAP, which indicated its higher bioabsorbability. Importantly, the biomaterials showed a similar level of biocompatibility and osteoconductivity regardless of the bioceramic type. Both scaffolds had the ability to induce apatite formation on their surfaces, proving their bioactive property, that is crucial for good implant osseointegration. In turn, performed biological experiments showed that tested bone scaffolds were non-toxic and their surfaces promoted cell proliferation and osteogenic differentiation. Moreover, the biomaterials did not exert a stimulatory effect on immune cells, since they did not generate excessive amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS), indicating a low risk of inflammatory response after implantation. In conclusion, based on the obtained results, both FAP- and HAP-based scaffolds have an appropriate microstructure and high biocompatibility, being promising biomaterials for bone regeneration applications. However, FAP-based biomaterial has higher bioabsorbability than the HAP-based scaffold, which is a very important property from the clinical point of view, because it enables a progressive replacement of the bone scaffold with newly formed bone tissue. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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29 pages, 8391 KiB

Open AccessArticle

The Influence of Novel, Biocompatible, and Bioresorbable Poly(3-hydroxyoctanoate) Dressings on Wound Healing in Mice

by Martyna Seta, Katarzyna Haraźna, Kaja Kasarełło, Daria Solarz-Keller, Agnieszka Cudnoch-Jędrzejewska, Tomasz Witko, Zenon Rajfur and Maciej Guzik

Int. J. Mol. Sci. 2022, 23(24), 16159; https://doi.org/10.3390/ijms232416159 - 18 Dec 2022

Cited by 5 | Viewed by 1823

Abstract

The human body’s natural protective barrier, the skin, is exposed daily to minor or major mechanical trauma, which can compromise its integrity. Therefore, the search for new dressing materials that can offer new functionalisation is fully justified. In this work, the development of two new types of dressings based on poly(3-hydroxyoctanoate) (P(3HO)) is presented. One of the groups was supplemented with conjugates of an anti-inflammatory substance (diclofenac) that was covalently linked to oligomers of hydroxycarboxylic acids (Oli-dicP(3HO)). The novel dressings were prepared using the solvent casting/particulate leaching technique. To our knowledge, this is the first paper in which P(3HO)-based dressings were used in mice wound treatment. The results of our research confirm that dressings based on P(3HO) are safe, do not induce an inflammatory response, reduce the expression of pro-inflammatory cytokines, provide adequate wound moisture, support angiogenesis, and, thanks to their hydrophobic characteristics, provide an ideal protective barrier. Newly designed dressings containing Oli-dicP(3HO) can promote tissue regeneration by partially reducing the inflammation at the injury site. To conclude, the presented materials might be potential candidates as excellent dressings for wound treatment. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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11 pages, 7182 KiB

Open AccessCommunication

Biocompatibility of a Ti-Rich Medium-Entropy Alloy with Glioblastoma Astrocytoma Cells

by Wen-Fu Ho, Ka-Kin Wong, Mei-Hwa Lee, James L. Thomas, Ya-Chun Chang, Shih-Ching Wu, Hsueh-Chuan Hsu and Hung-Yin Lin

Int. J. Mol. Sci. 2022, 23(23), 14552; https://doi.org/10.3390/ijms232314552 - 22 Nov 2022

Cited by 2 | Viewed by 1399

Abstract

Titanium and titanium alloys are widely used in medical devices and implants; thus, the biocompatibility of these metals is of great importance. In this study, glioblastoma astrocytoma cellular responses to Ti₆₅-Zr₁₈-Nb₁₆-Mo₁ (Ti65M, metastable medium-entropy alloy), Ti-13Nb-7Sn-4Mo (TNSM, titanium alloy), and commercially pure titanium (CP-Ti) were studied. Several physical parameters (crystal phase structure, surface roughness and hardness) of the titanium alloys were measured, and the correlation with the cellular viability was investigated. Finally, the relative protein expression in cellular proliferation pathways was measured and compared with mRNA expression assessed with quantitative real-time reverse transcription polymerase chain reaction assay (qRT-PCR). Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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22 pages, 7217 KiB

Open AccessArticle

Study on βTCP/P(3HB) Scaffolds—Physicochemical Properties and Biological Performance in Low Oxygen Concentration

by Szymon Skibiński, Joanna P. Czechowska, Ewelina Cichoń, Martyna Seta, Agata Gondek, Agnieszka Cudnoch-Jędrzejewska, Anna Ślósarczyk, Maciej Guzik and Aneta Zima

Int. J. Mol. Sci. 2022, 23(19), 11587; https://doi.org/10.3390/ijms231911587 - 30 Sep 2022

Cited by 4 | Viewed by 2092

Abstract

The search for new materials for bone regenerative purposes is still ongoing. Therefore, we present a series of newly constructed composites based on β tricalcium phosphate (βTCP) and poly(3-hydroxybutyrate) bacteria-derived biopolymer (P(3HB)) in the form of 3D scaffolds with different pore sizes. To improve the polymer attachment to the βTCP surface, the etching of ceramic sinters, using citric acid, was applied. As expected, pre-treatment led to the increase in surface roughness and the creation of micropores facilitating polymer adhesion. In this way, the durability and compressive strength of the ceramic–polymer scaffolds were enhanced. It was confirmed that P(3HB) degrades to 3-hydroxybutyric acid, which broadens applications of developed materials in bone tissue engineering as this compound can potentially nourish surrounding tissues and reduce osteoporosis. Moreover, to the best of our knowledge, it is one of the first studies where the impact of βTCP/P(3HB) scaffolds on mesenchymal stem cells (MSCs), cultured in lowered (5%) oxygen concentration, was assessed. It was decided to use a 5% oxygen concentration in the culture to mimic the conditions that would be found in damaged bone in a living organism during regeneration. Scaffolds enabled cell migration and sufficient flow of the culture medium, ensuring high cell viability. Furthermore, in composites with etched βTCP, the MSCs adhesion was facilitated by hydrophilic ceramic protrusions which reduced hydrophobicity. The developed materials are potential candidates for bone tissue regeneration. Nevertheless, to confirm this hypothesis, in vivo studies should be performed. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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19 pages, 3665 KiB

Open AccessArticle

Mesh Ti6Al4V Material Manufactured by Selective Laser Melting (SLM) as a Promising Intervertebral Fusion Cage

by Agata Przekora, Paulina Kazimierczak, Michal Wojcik, Emil Chodorski and Jacek Kropiwnicki

Int. J. Mol. Sci. 2022, 23(7), 3985; https://doi.org/10.3390/ijms23073985 - 3 Apr 2022

Cited by 7 | Viewed by 3002

Abstract

Intervertebral cages made of Ti6Al4V alloy show excellent osteoconductivity, but also higher stiffness, compared to commonly used polyether-ether-ketone (PEEK) materials, that may lead to a stress-shielding effect and implant subsidence. In this study, a metallic intervertebral fusion cage, with improved mechanical behavior, was manufactured by the introduction of a three-dimensional (3D) mesh structure to Ti6Al4V material, using an additive manufacturing method. Then, the mechanical and biological properties of the following were compared: (1) PEEK, with a solid structure, (2) 3D-printed Ti6Al4V, with a solid structure, and (3) 3D-printed Ti6Al4V, with a mesh structure. A load-induced subsidence test demonstrated that the 3D-printed mesh Ti6Al4V cage had significantly lower tendency (by 15%) to subside compared to the PEEK implant. Biological assessment of the samples proved that all tested materials were biocompatible. However, both titanium samples (solid and mesh) were characterized by significantly higher bioactivity, osteoconductivity, and mineralization ability, compared to PEEK. Moreover, osteoblasts revealed stronger adhesion to the surface of the Ti6Al4V samples compared to PEEK material. Thus, it was clearly shown that the 3D-printed mesh Ti6Al4V cage possesses all the features for optimal spinal implant, since it carries low risk of implant subsidence and provides good osseointegration at the bone-implant interface. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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Review

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21 pages, 4554 KiB

Open AccessReview

The Impact of Hydroxyapatite Sintering Temperature on Its Microstructural, Mechanical, and Biological Properties

by Marta Trzaskowska, Vladyslav Vivcharenko and Agata Przekora

Int. J. Mol. Sci. 2023, 24(6), 5083; https://doi.org/10.3390/ijms24065083 - 7 Mar 2023

Cited by 24 | Viewed by 4319

Abstract

Hydroxyapatite (HA), the principal mineral of bone tissue, can be fabricated as an artificial calcium phosphate (CaP) ceramic and potentially used as bioceramic material for bone defect treatment. Nevertheless, the production method (including the applied sintering temperature) of synthetic hydroxyapatite directly affects its basic properties, such as its microstructure, mechanical parameters, bioabsorbability, and osteoconductivity, and in turn influences its biomedical potential as an implantable biomaterial. The wide application of HA in regenerative medicine makes it necessary to explain the validity of the selection of the sintering temperature. The main emphasis of this article is on the description and summarization of the key features of HA depending on the applied sintering temperature during the synthesis process. The review is mainly focused on the dependence between the HA sintering temperature and its microstructural features, mechanical properties, biodegradability/bioabsorbability, bioactivity, and biocompatibility. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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23 pages, 2912 KiB

Open AccessReview

Vascularization Strategies in 3D Cell Culture Models: From Scaffold-Free Models to 3D Bioprinting

by Shamapto Guha Anthon and Karolina Papera Valente

Int. J. Mol. Sci. 2022, 23(23), 14582; https://doi.org/10.3390/ijms232314582 - 23 Nov 2022

Cited by 19 | Viewed by 5860

Abstract

The discrepancies between the findings in preclinical studies, and in vivo testing and clinical trials have resulted in the gradual decline in drug approval rates over the past decades. Conventional in vitro drug screening platforms employ two-dimensional (2D) cell culture models, which demonstrate inaccurate drug responses by failing to capture the three-dimensional (3D) tissue microenvironment in vivo. Recent advancements in the field of tissue engineering have made possible the creation of 3D cell culture systems that can accurately recapitulate the cell–cell and cell–extracellular matrix interactions, as well as replicate the intricate microarchitectures observed in native tissues. However, the lack of a perfusion system in 3D cell cultures hinders the establishment of the models as potential drug screening platforms. Over the years, multiple techniques have successfully demonstrated vascularization in 3D cell cultures, simulating in vivo-like drug interactions, proposing the use of 3D systems as drug screening platforms to eliminate the deviations between preclinical and in vivo testing. In this review, the basic principles of 3D cell culture systems are briefly introduced, and current research demonstrating the development of vascularization in 3D cell cultures is discussed, with a particular focus on the potential of these models as the future of drug screening platforms. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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38 pages, 9835 KiB

Open AccessReview

A Review on Stimuli-Actuated 3D Micro/Nanostructures for Tissue Engineering and the Potential of Laser-Direct Writing via Two-Photon Polymerization for Structure Fabrication

by Bogdan Stefanita Calin and Irina Alexandra Paun

Int. J. Mol. Sci. 2022, 23(22), 14270; https://doi.org/10.3390/ijms232214270 - 17 Nov 2022

Cited by 9 | Viewed by 2171

Abstract

In this review, we present the most recent and relevant research that has been done regarding the fabrication of 3D micro/nanostructures for tissue engineering applications. First, we make an overview of 3D micro/nanostructures that act as backbone constructs where the seeded cells can attach, proliferate and differentiate towards the formation of new tissue. Then, we describe the fabrication of 3D micro/nanostructures that are able to control the cellular processes leading to faster tissue regeneration, by actuation using topographical, mechanical, chemical, electric or magnetic stimuli. An in-depth analysis of the actuation of the 3D micro/nanostructures using each of the above-mentioned stimuli for controlling the behavior of the seeded cells is provided. For each type of stimulus, a particular recent application is presented and discussed, such as controlling the cell proliferation and avoiding the formation of a necrotic core (topographic stimulation), controlling the cell adhesion (nanostructuring), supporting the cell differentiation via nuclei deformation (mechanical stimulation), improving the osteogenesis (chemical and magnetic stimulation), controlled drug-delivery systems (electric stimulation) and fastening tissue formation (magnetic stimulation). The existing techniques used for the fabrication of such stimuli-actuated 3D micro/nanostructures, are briefly summarized. Special attention is dedicated to structures’ fabrication using laser-assisted technologies. The performances of stimuli-actuated 3D micro/nanostructures fabricated by laser-direct writing via two-photon polymerization are particularly emphasized. Full article

(This article belongs to the Special Issue Interactions of Cells with Biomaterials for Regenerative Medicine 3.0)

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