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Bioengineering
Special Issues
Applying Polymeric Biomaterials in 3D Tissue Constructs
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Applying Polymeric Biomaterials in 3D Tissue Constructs

A special issue of Bioengineering (ISSN 2306-5354).

Deadline for manuscript submissions: closed (25 August 2018) | Viewed by 38581

Special Issue Editor

Dr. Ferry Melchels

E-Mail Website
Guest Editor
Institute of Biological Chemistry, Biophysics and BioengineeringSchool of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, UK

Special Issue Information

Dear Colleagues,

Over the past decade, significant progress has been made in the evolution from 2D cell culture to 3D tissue culture. When cells are taken out of their native environment and cultured on a flat, hard substrate they start to loose many of their characteristics. In a well-designed 3D construct, cells of different types can interact with each other and their environment, stimulating them to form tissue, and to display behaviour as observed in vivo. Such tissue models can be used in vitro for drug screening, toxicology testing, or biological studies, or in vivo for regenerative medicine.

The application of polymers has greatly aided the development of 3D tissue models. Polymers can provide structural support as well as 3-dimensionality (hydrogels in particular), and they can present cells with attachments sites, biochemical cues and degradable links.

This Special Issue focuses on the application of polymers in 3D tissue constructs, where polymers can range from synthetic to naturally derived, and from hard scaffolding polymers to elastomers through to hydrogels. It aims to exhibit a sample of the state-of-the-art of the application of polymeric biomaterials in 3D tissue constructs.

Dr. Ferry Melchels
Guest Editor

Manuscript Submission Information

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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

  • Polymer
  • Hydrogel
  • Biomaterial
  • Tissue Engineering
  • 3D Culture
  • Scaffold
  • Biofabrication

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Published Papers (5 papers)

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Research

13 pages, 2326 KiB  
Article
3D Encapsulation Made Easy: A Coaxial-Flow Circuit for the Fabrication of Hydrogel Microfibers Patches
by Chiara Emma Campiglio, Francesca Ceriani and Lorenza Draghi
Bioengineering 2019, 6(2), 30; https://doi.org/10.3390/bioengineering6020030 - 6 Apr 2019
Cited by 6 | Viewed by 6730
Abstract
To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended [...] Read more.
To fully exploit the potential of hydrogel micro-fibers in the design of regenerative medicinal materials, we designed a simple, easy to replicate system for cell embedding in degradable fibrous scaffolds, and validated its effectiveness using alginate-based materials. For scaffold fabrication, cells are suspended in a hydrogel-precursor and injected in a closed-loop circuit, where a pump circulates the ionic cross-linking solution. The flow of the cross-linking solution stretches and solidifies a continuous micro-scaled, cell-loaded hydrogel fiber that whips, bends, and spontaneously assembles in a self-standing, spaghetti-like patch. After investigation and tuning of process- and solution-related parameters, homogeneous microfibers with controlled diameters and consistent scaffolds were obtained from different alginate concentrations and blends with biologically favorable macromolecules (i.e., gelatin or hyaluronic acid). Despite its simplicity, this coaxial-flow encapsulation system allows for the rapid and effortless fabrication of thick, well-defined scaffolds, with viable cells being homogeneously distributed within the fibers. The reduced fiber diameter and the inherent macro-porous structure that is created from the random winding of fibers can sustain mass transport, and support encapsulated cell survival. As different materials and formulations can be processed to easily create homogeneously cell-populated structures, this system appears as a valuable platform, not only for regenerative medicine, but also, more in general, for 3D cell culturing in vitro. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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14 pages, 4016 KiB  
Article
Thermoplastic PCL-b-PEG-b-PCL and HDI Polyurethanes for Extrusion-Based 3D-Printing of Tough Hydrogels
by Aysun Güney, Christina Gardiner, Andrew McCormack, Jos Malda and Dirk W. Grijpma
Bioengineering 2018, 5(4), 99; https://doi.org/10.3390/bioengineering5040099 - 14 Nov 2018
Cited by 30 | Viewed by 8813
Abstract
Novel tough hydrogel materials are required for 3D-printing applications. Here, a series of thermoplastic polyurethanes (TPUs) based on poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers and hexamethylene diisocyanate (HDI) were developed with PEG contents varying between 30 [...] Read more.
Novel tough hydrogel materials are required for 3D-printing applications. Here, a series of thermoplastic polyurethanes (TPUs) based on poly(ɛ-caprolactone)-b-poly(ethylene glycol)-b-poly(ɛ-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymers and hexamethylene diisocyanate (HDI) were developed with PEG contents varying between 30 and 70 mol%. These showed excellent mechanical properties not only when dry, but also when hydrated: TPUs prepared from PCL-b-PEG-b-PCL with PEG of Mn 6 kg/mol (PCL7-PEG6-PCL7) took up 122 wt.% upon hydration and had an E-modulus of 52 ± 10 MPa, a tensile strength of 17 ± 2 MPa, and a strain at break of 1553 ± 155% in the hydrated state. They had a fracture energy of 17976 ± 3011 N/mm2 and a high tearing energy of 72 kJ/m2. TPUs prepared using PEG with Mn of 10 kg/mol (PCL5-PEG10-PCL5) took up 534% water and were more flexible. When wet, they had an E-modulus of 7 ± 2 MPa, a tensile strength of 4 ± 1 MPa, and a strain at break of 147 ± 41%. These hydrogels had a fracture energy of 513 ± 267 N/mm2 and a tearing energy of 16 kJ/m2. The latter TPU was first extruded into filaments and then processed into designed porous hydrogel structures by 3D-printing. These hydrogels can be used in 3D printing of tissue engineering scaffolds with high fracture toughness. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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19 pages, 2280 KiB  
Article
A Standardized Collagen-Based Scaffold Improves Human Hepatocyte Shipment and Allows Metabolic Studies over 10 Days
by Marc Ruoß, Victor Häussling, Frank Schügner, Leon H. H. Olde Damink, Serene M. L. Lee, Liming Ge, Sabrina Ehnert and Andreas K. Nussler
Bioengineering 2018, 5(4), 86; https://doi.org/10.3390/bioengineering5040086 - 16 Oct 2018
Cited by 28 | Viewed by 7120
Abstract
Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has [...] Read more.
Due to pronounced species differences, hepatotoxicity of new drugs often cannot be detected in animal studies. Alternatively, human hepatocytes could be used, but there are some limitations. The cells are not always available on demand or in sufficient amounts, so far there has been only limited success to allow the transport of freshly isolated hepatocytes without massive loss of function or their cultivation for a long time. Since it is well accepted that the cultivation of hepatocytes in 3D is related to an improved function, we here tested the Optimaix-3D Scaffold from Matricel for the transport and cultivation of hepatocytes. After characterization of the scaffold, we shipped cells on the scaffold and/or cultivated them over 10 days. With the evaluation of hepatocyte functions such as urea production, albumin synthesis, and CYP activity, we showed that the metabolic activity of the cells on the scaffold remained nearly constant over the culture time whereas a significant decrease in metabolic activity occurred in 2D cultures. In addition, we demonstrated that significantly fewer cells were lost during transport. In summary, the collagen-based scaffold allows the transport and cultivation of hepatocytes without loss of function over 10 days. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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10 pages, 1975 KiB  
Article
Milieu for Endothelial Differentiation of Human Adipose-Derived Stem Cells
by Kendra Clark and Amol V. Janorkar
Bioengineering 2018, 5(4), 82; https://doi.org/10.3390/bioengineering5040082 - 3 Oct 2018
Cited by 11 | Viewed by 5617
Abstract
Human adipose-derived stem cells (hASCs) have been shown to differentiate down many lineages including endothelial lineage. We hypothesized that hASCs would more efficiently differentiate toward the endothelial lineage when formed as three-dimensional (3D) spheroids and with the addition of vascular endothelial growth factor [...] Read more.
Human adipose-derived stem cells (hASCs) have been shown to differentiate down many lineages including endothelial lineage. We hypothesized that hASCs would more efficiently differentiate toward the endothelial lineage when formed as three-dimensional (3D) spheroids and with the addition of vascular endothelial growth factor (VEGF). Three conditions were tested: uncoated tissue culture polystyrene (TCPS) surfaces that induced a 2D monolayer formation; elastin-like polypeptide (ELP)-collagen composite hydrogel scaffolds that induced encapsulated 3D spheroid culture; and ELP-polyethyleneimine-coated TCPS surfaces that induced 3D spheroid formation in scaffold-free condition. Cells were exposed to endothelial differentiation medium containing no additional VEGF or 20 and 50 ng/mL of VEGF for 7 days and assayed for viability and endothelial differentiation markers. While endothelial differentiation media supported endothelial differentiation of hASCs, our 3D spheroid cultures augmented this differentiation and produced more von Willebrand factor than 2D cultures. Likewise, 3D cultures were able to uptake LDL, whereas the 2D cultures were not. Higher concentrations of VEGF further enhanced differentiation. Establishing angiogenesis is a key factor in regenerative medicine. Future studies aim to elucidate how to produce physiological changes such as neoangiogenesis and sprouting of vessels which may enhance the survival of regenerated tissues. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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12 pages, 4756 KiB  
Article
A Three-Dimensional Collagen-Elastin Scaffold for Heart Valve Tissue Engineering
by Xinmei Wang, Mir S. Ali and Carla M. R. Lacerda
Bioengineering 2018, 5(3), 69; https://doi.org/10.3390/bioengineering5030069 - 28 Aug 2018
Cited by 41 | Viewed by 9373
Abstract
Since most of the body’s extracellular matrix (ECM) is composed of collagen and elastin, we believe the choice of these materials is key for the future and promise of tissue engineering. Once it is known how elastin content of ECM guides cellular behavior [...] Read more.
Since most of the body’s extracellular matrix (ECM) is composed of collagen and elastin, we believe the choice of these materials is key for the future and promise of tissue engineering. Once it is known how elastin content of ECM guides cellular behavior (in 2D or 3D), one will be able to harness the power of collagen-elastin microenvironments to design and engineer stimuli-responsive tissues. Moreover, the implementation of such matrices to promote endothelial-mesenchymal transition of primary endothelial cells constitutes a powerful tool to engineer 3D tissues. Here, we design a 3D collagen-elastin scaffold to mimic the native ECM of heart valves, by providing the strength of collagen layers, as well as elasticity. Valve interstitial cells (VICs) were encapsulated in the collagen-elastin hydrogels and valve endothelial cells (VECs) cultured onto the surface to create an in vitro 3D VEC-VIC co-culture. Over a seven-day period, VICs had stable expression levels of integrin β1 and F-actin and continuously proliferated, while cell morphology changed to more elongated. VECs maintained endothelial phenotype up to day five, as indicated by low expression of F-actin and integrin β1, while transformed VECs accounted for less than 7% of the total VECs in culture. On day seven, over 20% VECs were transformed to mesenchymal phenotype, indicated by increased actin filaments and higher expression of integrin β1. These findings demonstrate that our 3D collagen-elastin scaffolds provided a novel tool to study cell-cell or cell-matrix interactions in vitro, promoting advances in the current knowledge of valvular endothelial cell mesenchymal transition. Full article
(This article belongs to the Special Issue Applying Polymeric Biomaterials in 3D Tissue Constructs)
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