Bioprinting of Tissue-Engineered Scaffolds: Design Strategies & Printability of Smart Biomaterials

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 36215

Special Issue Editors


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Guest Editor
UCL Institute of Orthopaedic & Musculoskeletal Science, University College London, Bloomsbury, London WC1E 6BT, UK
Interests: biomaterials; tissue engineering; scaffold technology; orthopaedic bioengineering

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Guest Editor
Department of Mechanical Engineering, Division of Biomedical Engineering, University of Saskatchewan, Saskatoon, SK, Canada
Interests: tissue engineering; preoperative planning; biofabrication; customized scaffolds; 3D bioprinting; additive manufacturing; smart hydrogels & polymers; mechanical properties

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Guest Editor
Department of Orthopaedic Surgery & Musculoskeletal Medicine, Universityof Otago, Christchurch 8140, New Zealand
Interests: biomaterials; tissue engineering; hydrogels; 3D-printing

Special Issue Information

Dear Colleagues, 

Extrusion-based bioprinting, also known as the dispensing-based method, has been widely used to construct scaffolds made of biomaterials and cells. This technique is yet to be explored while facing challenges related to printability. Printability, as the critical issue in extrusion-based bioprinting, can affect cell fate as well as the mechanical properties of 3D scaffolds. Considerable progress has been achieved in synthesizing novel biomaterials with enhanced printability, as well as new design concepts. Additionally, other steps have been taken to optimize printing parameters/conditions, employing numerical modelling or indirect printing techniques. It is necessary to map the relationship between printability and inter-related factors, involving design, biomaterial, and biofabrication. This Special Issue aims to illustrate the recent development and advance in this field, including, but not limited to, biomaterials, design and fabrication of scaffolds, indirect bioprinting, 3D printing, fluid modelling, numerical modelling, characterization of biomaterials (hydrogels specifically), extrusion-based bioprinting for tissue engineering applications, crosslinking strategies, and therapeutic applications of extrusion-based bioprinting 

Prof. Dr. Chaozong Liu
Dr. Saman Naghieh
Dr. Gabriella Lindberg
Guest Editors

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Keywords

  • Additive Manufacturing
  • 3D Bioprinting
  • Design for Manufacturing
  • Crosslinking Mechanism
  • Smart Hydrogels/Biomaterials
  • Indirect Printing
  • Numerical Modelling
  • Tissue Engineering
  • Characterization
  • Cell Growth

Published Papers (7 papers)

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Research

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17 pages, 2882 KiB  
Article
3D Bioprinting of Novel κ-Carrageenan Bioinks: An Algae-Derived Polysaccharide
by Diana M. C. Marques, João C. Silva, Ana Paula Serro, Joaquim M. S. Cabral, Paola Sanjuan-Alberte and Frederico C. Ferreira
Bioengineering 2022, 9(3), 109; https://doi.org/10.3390/bioengineering9030109 - 6 Mar 2022
Cited by 23 | Viewed by 5121
Abstract
Novel green materials not sourced from animals and with low environmental impact are becoming increasingly appealing for biomedical and cellular agriculture applications. Marine biomaterials are a rich source of structurally diverse compounds with various biological activities. Kappa-carrageenan (κ-c) is a potential candidate for [...] Read more.
Novel green materials not sourced from animals and with low environmental impact are becoming increasingly appealing for biomedical and cellular agriculture applications. Marine biomaterials are a rich source of structurally diverse compounds with various biological activities. Kappa-carrageenan (κ-c) is a potential candidate for tissue engineering applications due to its gelation properties, mechanical strength, and similar structural composition of glycosaminoglycans (GAGs), possessing several advantages when compared to other algae-based materials typically used in bioprinting such as alginate. For those reasons, this material was selected as the main polysaccharide component of the bioinks developed herein. In this work, pristine κ-carrageenan bioinks were successfully formulated for the first time and used to fabricate 3D scaffolds by bioprinting. Ink formulation and printing parameters were optimized, allowing for the manufacturing of complex 3D structures. Mechanical compression tests and dry weight determination revealed young’s modulus between 24.26 and 99.90 kPa and water contents above 97%. Biocompatibility assays, using a mouse fibroblast cell line, showed high cell viability and attachment. The bioprinted cells were spread throughout the scaffolds with cells exhibiting a typical fibroblast-like morphology similar to controls. The 3D bio-/printed structures remained stable under cell culture conditions for up to 11 days, preserving high cell viability values. Overall, we established a strategy to manufacture 3D bio-/printed scaffolds through the formulation of novel bioinks with potential applications in tissue engineering and cellular agriculture. Full article
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17 pages, 3424 KiB  
Article
3D Printing of Abdominal Immobilization Masks for Therapeutics: Dosimetric, Mechanical and Financial Analysis
by Jessica Duarte, Maria Amélia Ramos Loja, Ricardo Portal and Lina Vieira
Bioengineering 2022, 9(2), 55; https://doi.org/10.3390/bioengineering9020055 - 29 Jan 2022
Cited by 1 | Viewed by 2776
Abstract
Molding immobilization masks is a time-consuming process, strongly dependent on the healthcare professional, and potentially uncomfortable for the patient. Thus, an alternative sustainable automated production process is proposed for abdominal masks, using fused deposition modelling (FDM) 3D printing with polylactic acid (PLA). Radiological [...] Read more.
Molding immobilization masks is a time-consuming process, strongly dependent on the healthcare professional, and potentially uncomfortable for the patient. Thus, an alternative sustainable automated production process is proposed for abdominal masks, using fused deposition modelling (FDM) 3D printing with polylactic acid (PLA). Radiological properties of PLA were evaluated by submitting a set of PLA plates to photon beam radiation, while estimations of their mechanical characteristics were assessed through numerical simulation. Based on the obtained results, the abdominal mask was 3D printed and process costs and times were analyzed. The plates revealed dose transmissions similar to the conventional mask at all energies, and mechanical deformation guarantees the required immobilization, with a 66% final cost reduction. PLA proved to be an excellent material for this purpose. Despite the increase in labour costs, a significant reduction in material costs is observed with the proposed process. However, the time results are not favorable, mainly due to the printing technique used in this study. Full article
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Review

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30 pages, 3051 KiB  
Review
Bioprinting Scaffolds for Vascular Tissues and Tissue Vascularization
by Peter Viktor Hauser, Hsiao-Min Chang, Masaki Nishikawa, Hiroshi Kimura, Norimoto Yanagawa and Morgan Hamon
Bioengineering 2021, 8(11), 178; https://doi.org/10.3390/bioengineering8110178 - 6 Nov 2021
Cited by 14 | Viewed by 5155
Abstract
In recent years, tissue engineering has achieved significant advancements towards the repair of damaged tissues. Until this day, the vascularization of engineered tissues remains a challenge to the development of large-scale artificial tissue. Recent breakthroughs in biomaterials and three-dimensional (3D) printing have made [...] Read more.
In recent years, tissue engineering has achieved significant advancements towards the repair of damaged tissues. Until this day, the vascularization of engineered tissues remains a challenge to the development of large-scale artificial tissue. Recent breakthroughs in biomaterials and three-dimensional (3D) printing have made it possible to manipulate two or more biomaterials with complementary mechanical and/or biological properties to create hybrid scaffolds that imitate natural tissues. Hydrogels have become essential biomaterials due to their tissue-like physical properties and their ability to include living cells and/or biological molecules. Furthermore, 3D printing, such as dispensing-based bioprinting, has progressed to the point where it can now be utilized to construct hybrid scaffolds with intricate structures. Current bioprinting approaches are still challenged by the need for the necessary biomimetic nano-resolution in combination with bioactive spatiotemporal signals. Moreover, the intricacies of multi-material bioprinting and hydrogel synthesis also pose a challenge to the construction of hybrid scaffolds. This manuscript presents a brief review of scaffold bioprinting to create vascularized tissues, covering the key features of vascular systems, scaffold-based bioprinting methods, and the materials and cell sources used. We will also present examples and discuss current limitations and potential future directions of the technology. Full article
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14 pages, 38118 KiB  
Review
Nanohydroxyapatite Electrodeposition onto Electrospun Nanofibers: Technique Overview and Tissue Engineering Applications
by Thiago Domingues Stocco, Pedro José Gomes Rodrigues, Mauricio Augusto de Almeida Filho and Anderson Oliveira Lobo
Bioengineering 2021, 8(11), 151; https://doi.org/10.3390/bioengineering8110151 - 22 Oct 2021
Cited by 3 | Viewed by 2367
Abstract
Nanocomposite scaffolds based on the combination of polymeric nanofibers with nanohydroxyapatite are a promising approach within tissue engineering. With this strategy, it is possible to synthesize nanobiomaterials that combine the well-known benefits and advantages of polymer-based nanofibers with the osteointegrative, osteoinductive, and osteoconductive [...] Read more.
Nanocomposite scaffolds based on the combination of polymeric nanofibers with nanohydroxyapatite are a promising approach within tissue engineering. With this strategy, it is possible to synthesize nanobiomaterials that combine the well-known benefits and advantages of polymer-based nanofibers with the osteointegrative, osteoinductive, and osteoconductive properties of nanohydroxyapatite, generating scaffolds with great potential for applications in regenerative medicine, especially as support for bone growth and regeneration. However, as efficiently incorporating nanohydroxyapatite into polymeric nanofibers is still a challenge, new methodologies have emerged for this purpose, such as electrodeposition, a fast, low-cost, adjustable, and reproducible technique capable of depositing coatings of nanohydroxyapatite on the outside of fibers, to improve scaffold bioactivity and cell–biomaterial interactions. In this short review paper, we provide an overview of the electrodeposition method, as well as a detailed discussion about the process of electrodepositing nanohydroxyapatite on the surface of polymer electrospun nanofibers. In addition, we present the main findings of the recent applications of polymeric micro/nanofibrous scaffolds coated with electrodeposited nanohydroxyapatite in tissue engineering. In conclusion, comments are provided about the future direction of nanohydroxyapatite electrodeposition onto polymeric nanofibers. Full article
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24 pages, 87969 KiB  
Review
The Importance of Mimicking Dermal-Epidermal Junction for Skin Tissue Engineering: A Review
by Mina Aleemardani, Michael Zivojin Trikić, Nicola Helen Green and Frederik Claeyssens
Bioengineering 2021, 8(11), 148; https://doi.org/10.3390/bioengineering8110148 - 20 Oct 2021
Cited by 25 | Viewed by 10474
Abstract
There is a distinct boundary between the dermis and epidermis in the human skin called the basement membrane, a dense collagen network that creates undulations of the dermal–epidermal junction (DEJ). The DEJ plays multiple roles in skin homeostasis and function, namely, enhancing the [...] Read more.
There is a distinct boundary between the dermis and epidermis in the human skin called the basement membrane, a dense collagen network that creates undulations of the dermal–epidermal junction (DEJ). The DEJ plays multiple roles in skin homeostasis and function, namely, enhancing the adhesion and physical interlock of the layers, creating niches for epidermal stem cells, regulating the cellular microenvironment, and providing a physical boundary layer between fibroblasts and keratinocytes. However, the primary role of the DEJ has been determined as skin integrity; there are still aspects of it that are poorly investigated. Tissue engineering (TE) has evolved promising skin regeneration strategies and already developed TE scaffolds for clinical use. However, the currently available skin TE equivalents neglect to replicate the DEJ anatomical structures. The emergent ability to produce increasingly complex scaffolds for skin TE will enable the development of closer physical and physiological mimics to natural skin; it also allows researchers to study the DEJ effect on cell function. Few studies have created patterned substrates that could mimic the human DEJ to explore their significance. Here, we first review the DEJ roles and then critically discuss the TE strategies to create the DEJ undulating structure and their effects. New approaches in this field could be instrumental for improving bioengineered skin substitutes, creating 3D engineered skin, identifying pathological mechanisms, and producing and screening drugs. Full article
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21 pages, 1474 KiB  
Review
Translational Application of 3D Bioprinting for Cartilage Tissue Engineering
by Sophie McGivern, Halima Boutouil, Ghayadah Al-Kharusi, Suzanne Little, Nicholas J. Dunne and Tanya J. Levingstone
Bioengineering 2021, 8(10), 144; https://doi.org/10.3390/bioengineering8100144 - 18 Oct 2021
Cited by 23 | Viewed by 4206
Abstract
Cartilage is an avascular tissue with extremely limited self-regeneration capabilities. At present, there are no existing treatments that effectively stop the deterioration of cartilage or reverse its effects; current treatments merely relieve its symptoms and surgical intervention is required when the condition aggravates. [...] Read more.
Cartilage is an avascular tissue with extremely limited self-regeneration capabilities. At present, there are no existing treatments that effectively stop the deterioration of cartilage or reverse its effects; current treatments merely relieve its symptoms and surgical intervention is required when the condition aggravates. Thus, cartilage damage remains an ongoing challenge in orthopaedics with an urgent need for improved treatment options. In recent years, major advances have been made in the development of three-dimensional (3D) bioprinted constructs for cartilage repair applications. 3D bioprinting is an evolutionary additive manufacturing technique that enables the precisely controlled deposition of a combination of biomaterials, cells, and bioactive molecules, collectively known as bioink, layer-by-layer to produce constructs that simulate the structure and function of native cartilage tissue. This review provides an insight into the current developments in 3D bioprinting for cartilage tissue engineering. The bioink and construct properties required for successful application in cartilage repair applications are highlighted. Furthermore, the potential for translation of 3D bioprinted constructs to the clinic is discussed. Overall, 3D bioprinting demonstrates great potential as a novel technique for the fabrication of tissue engineered constructs for cartilage regeneration, with distinct advantages over conventional techniques. Full article
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34 pages, 2891 KiB  
Review
Biofabrication Strategies for Musculoskeletal Disorders: Evolution towards Clinical Applications
by Saman Naghieh, Gabriella Lindberg, Maryam Tamaddon and Chaozong Liu
Bioengineering 2021, 8(9), 123; https://doi.org/10.3390/bioengineering8090123 - 10 Sep 2021
Cited by 13 | Viewed by 4148
Abstract
Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue [...] Read more.
Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance. Full article
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