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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 (27 February 2024) | Viewed by 64059

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Special Issue Editors

Dr. Loredana De Bartolo

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CNR- Istituto per la Tecnologia delle Membrane, Rende, Italy
Interests: bioreactors; membranes; interfaces; bioartificial organs/tissues; cell–material interactions
Special Issues, Collections and Topics in MDPI journals

Dr. Antonella Piscioneri

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Guest Editor

National Research Council of Italy, Institute on Membrane Technology, CNR-ITM, Via P. Bucci, cubo 17/C, I-87036 Rende, CS, Italy
Interests: tissue engineering; in vitro platform for disease modeling; membrane devices; biomimetic cell culture systems
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Prof. Dr. Seeram Ramakrishna

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Guest Editor

Department of Mechanical Engineering, National University of Singapore, Singapore 119077, Singapore
Interests: circular economy; sustainability; energy; biomaterials; nanofibers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Research strategies are focusing on new bioinspired approaches for the design of biomaterials and devices to be used for repairing and/or regenerating tissues and organs as well as for creating in vitro physiologically relevant models. More importantly, biomaterials can be designed to exhibit ECM micro- to nanoscale of chemistry and topography providing physical, chemical, and mechanical signals to the cells that generate the appropriate responses for the formation of a new organ or tissue. It is a proof of concept that the intrinsic characteristic of the biomaterials (e.g., topography, elastic modulus, chemistry, morphology) strongly influences and modulates the expansion and differentiation of cells in a 3D microenvironment. The complexity of the natural cellular environment can be recapitulated using devices such as bioreactors and microfluidic platforms overcoming limitations of the traditional culture systems and allowing a continuous perfusion of cells with nutrients and metabolites and the removal of catabolites and specific products. This system mimicking the venous and arterious network holds the homeostasis of the cellular environment, in combination with highly sensitive biosensors, which permit detecting and controlling the biological analytes. This Special Issue aims to enphasize current advances in bioinspired/biomimetic materials and devices providing insights into how they can be translated into cutting-edge biomedical applications.

Smart multifunctional and intelligent biomaterials with instructive, inductive, and triggering properties able to activate tissue regeneration can be fabricated using natural and synthetic polymers and inorganic and/or composites with an array of processing methods and technologies. This article collection offers an exploration of the latest trends in the development of different interfaces and devices for tissue/organ repair and regeneration. Innovative investigations on new biomimetic tissues and organs for drug testing/delivery and disease modeling will also be included. This Special Issue will include original articles as well as reviews on these topics.

Dr. Loredana De Bartolo
Dr. Antonella Piscioneri
Prof. Dr. Seeram Ramakrishna
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Keywords

Biomaterials
Bioreactors
Microfluidic devices
Biomimetic interfaces
Biofabrication
Nanomaterials
Self-assembling
Microtissues: organoids/spheroids
2D materials and 3D scaffolds
Biofunctionalization
In vitro culture systems
Cell–material interactions
Disease modelling
Drug testing/delivery
Intelligent biomaterials

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Published Papers (9 papers)

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Editorial

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3 pages, 180 KiB

Open AccessEditorial

Future Trends in Biomaterials and Devices for Cells and Tissues

by Loredana De Bartolo, Antonella Piscioneri and Seeram Ramakrishna

Int. J. Mol. Sci. 2023, 24(4), 3309; https://doi.org/10.3390/ijms24043309 - 7 Feb 2023

Viewed by 1655

Abstract

Setting up physiologically relevant in vitro models requires realizing a proper hierarchical cellular structure, wherein the main tissue features are recapitulated [...] Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

Research

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16 pages, 8055 KiB

Open AccessArticle

Patient-Derived Tumor Organoids for Guidance of Personalized Drug Therapies in Recurrent Glioblastoma

by Miriam Ratliff, Hichul Kim, Hao Qi, Minsung Kim, Bosung Ku, Daniel Dominguez Azorin, David Hausmann, Rajiv K. Khajuria, Areeba Patel, Elena Maier, Loic Cousin, Arnaud Ogier, Felix Sahm, Nima Etminan, Lukas Bunse, Frank Winkler, Victoria El-Khoury, Michael Platten and Yong-Jun Kwon

Int. J. Mol. Sci. 2022, 23(12), 6572; https://doi.org/10.3390/ijms23126572 - 12 Jun 2022

Cited by 19 | Viewed by 8686

Abstract

An obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors. Here, we describe our establishment of a PD-GBO-based functional profiling platform and the results of its application to four patient tumors. We show that our PD-GBO model system preserves key features of individual patient glioblastomas in vivo. As proof of concept, we tested a panel of 41 FDA-approved drugs and were able to identify potential treatment options for three out of four patients; the turnaround from tumor resection to discovery of treatment option was 13, 14, and 15 days, respectively. These results demonstrate that this approach is a complement and, potentially, an alternative to current molecular profiling efforts in the pursuit of effective personalized treatment discovery in a clinically relevant time period. Furthermore, these results warrant the use of PD-GBO platforms for preclinical identification of new drugs against defined morphological glioblastoma features. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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13 pages, 1608 KiB

Open AccessArticle

Alternative Brain Slice-on-a-Chip for Organotypic Culture and Effective Fluorescence Injection Testing

by Pedro Herreros, Silvia Tapia-González, Laura Sánchez-Olivares, María Fe Laguna Heras and Miguel Holgado

Int. J. Mol. Sci. 2022, 23(5), 2549; https://doi.org/10.3390/ijms23052549 - 25 Feb 2022

Cited by 9 | Viewed by 3590

Abstract

Mouse brain slices are one of the most common models to study brain development and functioning, increasing the number of study models that integrate microfluidic systems for hippocampal slice cultures. This report presents an alternative brain slice-on-a-chip, integrating an injection system inside the chip to dispense a fluorescent dye for long-term monitoring. Hippocampal slices have been cultured inside these chips, observing fluorescence signals from living cells, maintaining the cytoarchitecture of the slices. Having fluorescence images of biological samples inside the chip demonstrates the effectiveness of the staining process using the injection method avoiding leaks or biological contamination. The technology developed in this study presents a significant improvement in the local administration of reagents within a brain slice-on-a-chip system, which could be a suitable option for organotypic cultures in a microfluidic chip acting as a highly effective bioreactor. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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16 pages, 3236 KiB

Open AccessArticle

Inhibition of Tunneling Nanotubes between Cancer Cell and the Endothelium Alters the Metastatic Phenotype

by Chinmayee Dash, Tanmoy Saha, Shiladitya Sengupta and Hae Lin Jang

Int. J. Mol. Sci. 2021, 22(11), 6161; https://doi.org/10.3390/ijms22116161 - 7 Jun 2021

Cited by 15 | Viewed by 5340

Abstract

The interaction of tumor cells with blood vessels is one of the key steps during cancer metastasis. Metastatic cancer cells exhibit phenotypic state changes during this interaction: (1) they form tunneling nanotubes (TNTs) with endothelial cells, which act as a conduit for intercellular communication; and (2) metastatic cancer cells change in order to acquire an elongated phenotype, instead of the classical cellular aggregates or mammosphere-like structures, which it forms in three-dimensional cultures. Here, we demonstrate mechanistically that a siRNA-based knockdown of the exocyst complex protein Sec3 inhibits TNT formation. Furthermore, a set of pharmacological inhibitors for Rho GTPase–exocyst complex-mediated cytoskeletal remodeling is introduced, which inhibits TNT formation, and induces the reversal of the more invasive phenotype of cancer cell (spindle-like) into a less invasive phenotype (cellular aggregates or mammosphere). Our results offer mechanistic insights into this nanoscale communication and shift of phenotypic state during cancer–endothelial interactions. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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27 pages, 5957 KiB

Open AccessArticle

Heparin-Tagged PLA-PEG Copolymer-Encapsulated Biochanin A-Loaded (Mg/Al) LDH Nanoparticles Recommended for Non-Thrombogenic and Anti-Proliferative Stent Coating

by Shivakalyani Adepu, Hongrong Luo and Seeram Ramakrishna

Int. J. Mol. Sci. 2021, 22(11), 5433; https://doi.org/10.3390/ijms22115433 - 21 May 2021

Cited by 11 | Viewed by 3275

Abstract

Drug-eluting stents have been widely implanted to prevent neointimal hyperplasia associated with bare metal stents. Conventional polymers and anti-proliferative drugs suffer from stent thrombosis due to the non-selective nature of the drugs and hypersensitivity to polymer degradation products. Alternatively, various herbal anti-proliferative agents are sought, of which biochanin A (an isoflavone phytoestrogen) was known to have anti-proliferative and vasculoprotective action. PLA-PEG diblock copolymer was tagged with heparin, whose degradation releases heparin locally and prevents thrombosis. To get a controlled drug release, biochanin A was loaded in layered double hydroxide nanoparticles (LDH), which are further encapsulated in a heparin-tagged PLA-PEG copolymer. LDH nanoparticles are synthesized by a co-precipitation process; in situ as well as ex situ loading of biochanin A were done. PLA-PEG-heparin copolymer was synthesized by esterification reaction, and the drug-loaded nanoparticles are coated. The formulation was characterized by FTIR, XRD, DSC, DLS, and TEM. In vitro drug release studies, protein adhesion, wettability, hemocompatibility, and degradation studies were performed. The drug release was modeled by mathematical models to further emphasize the mechanism of drug release. The developed drug-eluting stent coating is non-thrombogenic, and it offers close to zero-order release for 40 days, with complete polymer degradation in 14 weeks. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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14 pages, 7756 KiB

Open AccessArticle

Venous and Arterial Endothelial Cells from Human Umbilical Cords: Potential Cell Sources for Cardiovascular Research

by Skadi Lau, Manfred Gossen, Andreas Lendlein and Friedrich Jung

Int. J. Mol. Sci. 2021, 22(2), 978; https://doi.org/10.3390/ijms22020978 - 19 Jan 2021

Cited by 30 | Viewed by 5465

Abstract

Although cardiovascular devices are mostly implanted in arteries or to replace arteries, in vitro studies on implant endothelialization are commonly performed with human umbilical cord-derived venous endothelial cells (HUVEC). In light of considerable differences, both morphologically and functionally, between arterial and venous endothelial cells, we here compare HUVEC and human umbilical cord-derived arterial endothelial cells (HUAEC) regarding their equivalence as an endothelial cell in vitro model for cardiovascular research. No differences were found in either for the tested parameters. The metabolic activity and lactate dehydrogenase, an indicator for the membrane integrity, slightly decreased over seven days of cultivation upon normalization to the cell number. The amount of secreted nitrite and nitrate, as well as prostacyclin per cell, also decreased slightly over time. Thromboxane B2 was secreted in constant amounts per cell at all time points. The Von Willebrand factor remained mainly intracellularly up to seven days of cultivation. In contrast, collagen and laminin were secreted into the extracellular space with increasing cell density. Based on these results one might argue that both cell types are equally suited for cardiovascular research. However, future studies should investigate further cell functionalities, and whether arterial endothelial cells from implantation-relevant areas, such as coronary arteries in the heart, are superior to umbilical cord-derived endothelial cells. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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Review

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41 pages, 9991 KiB

Open AccessReview

Surface Engineering Strategies to Enhance the In Situ Performance of Medical Devices Including Atomic Scale Engineering

by Afreen Sultana, Mina Zare, Hongrong Luo and Seeram Ramakrishna

Int. J. Mol. Sci. 2021, 22(21), 11788; https://doi.org/10.3390/ijms222111788 - 30 Oct 2021

Cited by 17 | Viewed by 4837

Abstract

Decades of intense scientific research investigations clearly suggest that only a subset of a large number of metals, ceramics, polymers, composites, and nanomaterials are suitable as biomaterials for a growing number of biomedical devices and biomedical uses. However, biomaterials are prone to microbial infection due to Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), hepatitis, tuberculosis, human immunodeficiency virus (HIV), and many more. Hence, a range of surface engineering strategies are devised in order to achieve desired biocompatibility and antimicrobial performance in situ. Surface engineering strategies are a group of techniques that alter or modify the surface properties of the material in order to obtain a product with desired functionalities. There are two categories of surface engineering methods: conventional surface engineering methods (such as coating, bioactive coating, plasma spray coating, hydrothermal, lithography, shot peening, and electrophoretic deposition) and emerging surface engineering methods (laser treatment, robot laser treatment, electrospinning, electrospray, additive manufacturing, and radio frequency magnetron sputtering technique). Atomic-scale engineering, such as chemical vapor deposition, atomic layer etching, plasma immersion ion deposition, and atomic layer deposition, is a subsection of emerging technology that has demonstrated improved control and flexibility at finer length scales than compared to the conventional methods. With the advancements in technologies and the demand for even better control of biomaterial surfaces, research efforts in recent years are aimed at the atomic scale and molecular scale while incorporating functional agents in order to elicit optimal in situ performance. The functional agents include synthetic materials (monolithic ZnO, quaternary ammonium salts, silver nano-clusters, titanium dioxide, and graphene) and natural materials (chitosan, totarol, botanical extracts, and nisin). This review highlights the various strategies of surface engineering of biomaterial including their functional mechanism, applications, and shortcomings. Additionally, this review article emphasizes atomic scale engineering of biomaterials for fabricating antimicrobial biomaterials and explores their challenges. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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18 pages, 3361 KiB

Open AccessReview

pHEMA: An Overview for Biomedical Applications

by Mina Zare, Ashkan Bigham, Mohamad Zare, Hongrong Luo, Erfan Rezvani Ghomi and Seeram Ramakrishna

Int. J. Mol. Sci. 2021, 22(12), 6376; https://doi.org/10.3390/ijms22126376 - 15 Jun 2021

Cited by 122 | Viewed by 12165

Abstract

Poly(2-hydroxyethyl methacrylate) (pHEMA) as a biomaterial with excellent biocompatibility and cytocompatibility elicits a minimal immunological response from host tissue making it desirable for different biomedical applications. This article seeks to provide an in-depth overview of the properties and biomedical applications of pHEMA for bone tissue regeneration, wound healing, cancer therapy (stimuli and non-stimuli responsive systems), and ophthalmic applications (contact lenses and ocular drug delivery). As this polymer has been widely applied in ophthalmic applications, a specific consideration has been devoted to this field. Pure pHEMA does not possess antimicrobial properties and the site where the biomedical device is employed may be susceptible to microbial infections. Therefore, antimicrobial strategies such as the use of silver nanoparticles, antibiotics, and antimicrobial agents can be utilized to protect against infections. Therefore, the antimicrobial strategies besides the drug delivery applications of pHEMA were covered. With continuous research and advancement in science and technology, the outlook of pHEMA is promising as it will most certainly be utilized in more biomedical applications in the near future. The aim of this review was to bring together state-of-the-art research on pHEMA and their applications. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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21 pages, 7015 KiB

Open AccessReview

3D Bioprinting of Human Tissues: Biofabrication, Bioinks, and Bioreactors

by Jianhua Zhang, Esther Wehrle, Marina Rubert and Ralph Müller

Int. J. Mol. Sci. 2021, 22(8), 3971; https://doi.org/10.3390/ijms22083971 - 12 Apr 2021

Cited by 143 | Viewed by 15881

Abstract

The field of tissue engineering has progressed tremendously over the past few decades in its ability to fabricate functional tissue substitutes for regenerative medicine and pharmaceutical research. Conventional scaffold-based approaches are limited in their capacity to produce constructs with the functionality and complexity of native tissue. Three-dimensional (3D) bioprinting offers exciting prospects for scaffolds fabrication, as it allows precise placement of cells, biochemical factors, and biomaterials in a layer-by-layer process. Compared with traditional scaffold fabrication approaches, 3D bioprinting is better to mimic the complex microstructures of biological tissues and accurately control the distribution of cells. Here, we describe recent technological advances in bio-fabrication focusing on 3D bioprinting processes for tissue engineering from data processing to bioprinting, mainly inkjet, laser, and extrusion-based technique. We then review the associated bioink formulation for 3D bioprinting of human tissues, including biomaterials, cells, and growth factors selection. The key bioink properties for successful bioprinting of human tissue were summarized. After bioprinting, the cells are generally devoid of any exposure to fluid mechanical cues, such as fluid shear stress, tension, and compression, which are crucial for tissue development and function in health and disease. The bioreactor can serve as a simulator to aid in the development of engineering human tissues from in vitro maturation of 3D cell-laden scaffolds. We then describe some of the most common bioreactors found in the engineering of several functional tissues, such as bone, cartilage, and cardiovascular applications. In the end, we conclude with a brief insight into present limitations and future developments on the application of 3D bioprinting and bioreactor systems for engineering human tissue. Full article

(This article belongs to the Special Issue Future Trends in Biomaterials and Devices for Cells and Tissues)

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