Advances in Biofabrication for Tissue Engineering and Regenerative Medicine Applications

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (5 February 2021) | Viewed by 25573

Special Issue Editors


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Guest Editor
Department of Mechanical, Aerospace and Civil Engineering, School of Engineering, Faculty of Science and Engineering & Henry Royce Institute, The University of Manchester, Manchester, UK
Interests: biofabrication; biomaterials; tissue engineering; cartilage

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Guest Editor
Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PL, UK
Interests: tissue engineering; biopolymers; bioprinting; rheology; biomaterials; cell biology

Special Issue Information

Dear Colleagues

Biofabrication strategies, and in particular 3D bioprinting, continue to gain interest for the generation of high-fidelity tissue-engineered structures for regenerative medicine, disease modelling and drug discovery applications. A global research effort over the last few decades has led to considerable advances in both the capability of bioprinting platforms and the variety of biomaterials that can be used. Consequently, the market for 3D bioprinting technologies is predicted to reach in excess of $1.6 billion by 2024.

The constant innovation of bioprinting strategies has led to successful applications in a wide variety of healthcare applications. Advances are not, however, limited to improvements in the bioprinting platform itself. The design of appropriate biomaterial-based bioinks is equally essential to the generation of a successful strategy. The mechanical behavior of candidate materials should suit the bioprinting strategy whilst simultaneously not hindering the key cellular mechanisms that are essential in a particular application.

The aim of this Special Issue is to highlight new approaches in the biofabrication of biological structures including, but not limited to, the development of novel bioprinting strategies and the design of cutting-edge biomaterial systems.

Dr Marco Domingos and Dr Samuel Moxon

Guest Editors

Dr. Marco Domingos
Dr. Samuel Moxon
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Polymers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tissue engineering
  • regenerative medicine
  • biofabrication
  • bioprinting
  • 3D printing
  • biomaterials
  • polymers
  • bioinks

Published Papers (6 papers)

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Editorial

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2 pages, 157 KiB  
Editorial
Advances in Biofabrication for Tissue Engineering and Regenerative Medicine Applications
by Marco Domingos and Sam Moxon
Polymers 2021, 13(9), 1522; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13091522 - 09 May 2021
Cited by 2 | Viewed by 1588
Abstract
Biofabrication strategies continue to gain considerable interest in the efforts to develop methods for better replicating in vitro models of human tissues [...] Full article

Research

Jump to: Editorial

18 pages, 2826 KiB  
Article
A Versatile Open-Source Printhead for Low-Cost 3D Microextrusion-Based Bioprinting
by Andres Sanz-Garcia, Enrique Sodupe-Ortega, Alpha Pernía-Espinoza, Tatsuya Shimizu and Carmen Escobedo-Lucea
Polymers 2020, 12(10), 2346; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12102346 - 13 Oct 2020
Cited by 14 | Viewed by 4430
Abstract
Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of Tissue engineering (TE) is still limited due to their cost or difficulty [...] Read more.
Three-dimensional (3D) bioprinting promises to be essential in tissue engineering for solving the rising demand for organs and tissues. Some bioprinters are commercially available, but their impact on the field of Tissue engineering (TE) is still limited due to their cost or difficulty to tune. Herein, we present a low-cost easy-to-build printhead for microextrusion-based bioprinting (MEBB) that can be installed in many desktop 3D printers to transform them into 3D bioprinters. We can extrude bioinks with precise control of print temperature between 2–60 °C. We validated the versatility of the printhead, by assembling it in three low-cost open-source desktop 3D printers. Multiple units of the printhead can also be easily put together in a single printer carriage for building a multi-material 3D bioprinter. Print resolution was evaluated by creating representative calibration models at different temperatures using natural hydrogels such as gelatin and alginate, and synthetic ones like poloxamer. Using one of the three modified low-cost 3D printers, we successfully printed cell-laden lattice constructs with cell viabilities higher than 90% after 24-h post printing. Controlling temperature and pressure according to the rheological properties of the bioinks was essential in achieving optimal printability and great cell viability. The cost per unit of our device, which can be used with syringes of different volume, is less expensive than any other commercially available product. These data demonstrate an affordable open-source printhead with the potential to become a reliable alternative to commercial bioprinters for any laboratory. Full article
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20 pages, 5276 KiB  
Article
Towards 3D Multi-Layer Scaffolds for Periodontal Tissue Engineering Applications: Addressing Manufacturing and Architectural Challenges
by Marta Porta, Chiara Tonda-Turo, Daniele Pierantozzi, Gianluca Ciardelli and Elena Mancuso
Polymers 2020, 12(10), 2233; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12102233 - 28 Sep 2020
Cited by 17 | Viewed by 3639
Abstract
Reduced periodontal support, deriving from chronic inflammatory conditions, such as periodontitis, is one of the main causes of tooth loss. The use of dental implants for the replacement of missing teeth has attracted growing interest as a standard procedure in clinical practice. However, [...] Read more.
Reduced periodontal support, deriving from chronic inflammatory conditions, such as periodontitis, is one of the main causes of tooth loss. The use of dental implants for the replacement of missing teeth has attracted growing interest as a standard procedure in clinical practice. However, adequate bone volume and soft tissue augmentation at the site of the implant are important prerequisites for successful implant positioning as well as proper functional and aesthetic reconstruction of patients. Three-dimensional (3D) scaffolds have greatly contributed to solve most of the challenges that traditional solutions (i.e., autografts, allografts and xenografts) posed. Nevertheless, mimicking the complex architecture and functionality of the periodontal tissue represents still a great challenge. In this study, a porous poly(ε-caprolactone) (PCL) and Sr-doped nano hydroxyapatite (Sr-nHA) with a multi-layer structure was produced via a single-step additive manufacturing (AM) process, as a potential strategy for hard periodontal tissue regeneration. Physicochemical characterization was conducted in order to evaluate the overall scaffold architecture, topography, as well as porosity with respect to the original CAD model. Furthermore, compressive tests were performed to assess the mechanical properties of the resulting multi-layer structure. Finally, in vitro biological performance, in terms of biocompatibility and osteogenic potential, was evaluated by using human osteosarcoma cells. The manufacturing route used in this work revealed a highly versatile method to fabricate 3D multi-layer scaffolds with porosity levels as well as mechanical properties within the range of dentoalveolar bone tissue. Moreover, the single step process allowed the achievement of an excellent integrity among the different layers of the scaffold. In vitro tests suggested the promising role of the ceramic phase within the polymeric matrix towards bone mineralization processes. Overall, the results of this study demonstrate that the approach undertaken may serve as a platform for future advances in 3D multi-layer and patient-specific strategies that may better address complex periodontal tissue defects. Full article
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14 pages, 11643 KiB  
Article
3D Printed Polycaprolactone/Gelatin/Bacterial Cellulose/Hydroxyapatite Composite Scaffold for Bone Tissue Engineering
by Abdullah M. Cakmak, Semra Unal, Ali Sahin, Faik N. Oktar, Mustafa Sengor, Nazmi Ekren, Oguzhan Gunduz and Deepak M. Kalaskar
Polymers 2020, 12(9), 1962; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12091962 - 29 Aug 2020
Cited by 79 | Viewed by 7270
Abstract
Three-dimensional (3D) printing application is a promising method for bone tissue engineering. For enhanced bone tissue regeneration, it is essential to have printable composite materials with appealing properties such as construct porous, mechanical strength, thermal properties, controlled degradation rates, and the presence of [...] Read more.
Three-dimensional (3D) printing application is a promising method for bone tissue engineering. For enhanced bone tissue regeneration, it is essential to have printable composite materials with appealing properties such as construct porous, mechanical strength, thermal properties, controlled degradation rates, and the presence of bioactive materials. In this study, polycaprolactone (PCL), gelatin (GEL), bacterial cellulose (BC), and different hydroxyapatite (HA) concentrations were used to fabricate a novel PCL/GEL/BC/HA composite scaffold using 3D printing method for bone tissue engineering applications. Pore structure, mechanical, thermal, and chemical analyses were evaluated. 3D scaffolds with an ideal pore size (~300 µm) for use in bone tissue engineering were generated. The addition of both bacterial cellulose (BC) and hydroxyapatite (HA) into PCL/GEL scaffold increased cell proliferation and attachment. PCL/GEL/BC/HA composite scaffolds provide a potential for bone tissue engineering applications. Full article
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19 pages, 4086 KiB  
Article
Topography-Mediated Myotube and Endothelial Alignment, Differentiation, and Extracellular Matrix Organization for Skeletal Muscle Engineering
by Ana Maria Almonacid Suarez, Marja G. L. Brinker, Linda A. Brouwer, Iris van der Ham, Martin C. Harmsen and Patrick van Rijn
Polymers 2020, 12(9), 1948; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12091948 - 28 Aug 2020
Cited by 11 | Viewed by 3885
Abstract
Understanding the response of endothelial cells to aligned myotubes is important to create an appropriate environment for tissue-engineered vascularized skeletal muscle. Part of the native tissue environment is the extracellular matrix (ECM). The ECM is a supportive scaffold for cells and allows cellular [...] Read more.
Understanding the response of endothelial cells to aligned myotubes is important to create an appropriate environment for tissue-engineered vascularized skeletal muscle. Part of the native tissue environment is the extracellular matrix (ECM). The ECM is a supportive scaffold for cells and allows cellular processes such as proliferation, differentiation, and migration. Interstitial matrix and basal membrane both comprise proteinaceous and polysaccharide components for strength, architecture, and volume retention. Virtually all cells are anchored to their basal lamina. One of the physical factors that affects cell behavior is topography, which plays an important role on cell alignment. We tested the hypothesis that topography-driven aligned human myotubes promote and support vascular network formation as a prelude to in vitro engineered vascularized skeletal muscle. Therefore, we used a PDMS-based topography substrate to investigate the influence of pre-aligned myotubes on the network formation of microvascular endothelial cells. The aligned myotubes produced a network of collagen fibers and laminin. This network supported early stages of endothelial network formation. Full article
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15 pages, 3404 KiB  
Article
A Preliminary Evaluation of the Pro-Chondrogenic Potential of 3D-Bioprinted Poly(ester Urea) Scaffolds
by Samuel R. Moxon, Miguel J.S. Ferreira, Patricia dos Santos, Bogdan Popa, Antonio Gloria, Ramaz Katsarava, David Tugushi, Armenio C. Serra, Nigel M. Hooper, Susan J. Kimber, Ana C. Fonseca and Marco A. N. Domingos
Polymers 2020, 12(7), 1478; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12071478 - 30 Jun 2020
Cited by 9 | Viewed by 3842
Abstract
Degeneration of articular cartilage (AC) is a common healthcare issue that can result in significantly impaired function and mobility for affected patients. The avascular nature of the tissue strongly burdens its regenerative capacity contributing to the development of more serious conditions such as [...] Read more.
Degeneration of articular cartilage (AC) is a common healthcare issue that can result in significantly impaired function and mobility for affected patients. The avascular nature of the tissue strongly burdens its regenerative capacity contributing to the development of more serious conditions such as osteoarthritis. Recent advances in bioprinting have prompted the development of alternative tissue engineering therapies for the generation of AC. Particular interest has been dedicated to scaffold-based strategies where 3D substrates are used to guide cellular function and tissue ingrowth. Despite its extensive use in bioprinting, the application of polycaprolactone (PCL) in AC is, however, restricted by properties that inhibit pro-chondrogenic cell phenotypes. This study proposes the use of a new bioprintable poly(ester urea) (PEU) material as an alternative to PCL for the generation of an in vitro model of early chondrogenesis. The polymer was successfully printed into 3D constructs displaying adequate substrate stiffness and increased hydrophilicity compared to PCL. Human chondrocytes cultured on the scaffolds exhibited higher cell viability and improved chondrogenic phenotype with upregulation of genes associated with type II collagen and aggrecan synthesis. Bioprinted PEU scaffolds could, therefore, provide a potential platform for the fabrication of bespoke, pro-chondrogenic tissue engineering constructs. Full article
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