Special Issue "Design of Bioreactor Systems for Tissue Engineering"

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A special issue of Processes (ISSN 2227-9717).

Deadline for manuscript submissions: closed (15 February 2014)

Special Issue Editor

Guest Editor
Prof. Dr. Julian Chaudhuri

Faculty of Engineering and Informatics, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK
Website | E-Mail
Phone: +44 1274 234021
Interests: regenerative medicine; tissue engineering; bioreactors; stem cell bioprocessing

Special Issue Information

Dear Colleagues,

This special issue of Processes will consider papers in the general area of Design of Bioreactor Systems for Tissue Engineering. The objective of this issue is to showcase the diversity and advances in research that contributes to developing effective systems for the culture and controlled differentiation of stem cells, or the combination of cells and biomaterials into functional tissue. There are a range of topics that contribute to “bioreactor systems” that include the following: cell culture and differentiation, culture on or in 3D scaffolds, bioprocessing considerations such as scale-up and monitoring and control, bioreactor design, membranes and other perfusion systems, co-culture, adherent or suspension cell culture, mathematical models, in vitro models, nutrient diffusion and mass transfer in 3D, fluid dynamics and shear.

We are particularly interested in receiving manuscripts that integrate biology and engineering research and/or experimental and theoretical studies. We invite researchers and practitioners from all areas of regenerative medicine to submit manuscripts for this important special issue of Processes.

Prof. Dr. Julian Chaudhuri
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed Open Access quarterly 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 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • cell culture
  • scaffolds
  • bioprocessing
  • scale-up
  • monitoring and control
  • mathematical models
  • stem cell differentiation
  • bioreactor design
  • membranes
  • diffusion and mass transfer

Published Papers (15 papers)

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Editorial

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Open AccessEditorial Special Issue: Design of Bioreactor Systems for Tissue Engineering
Processes 2015, 3(1), 46-49; doi:10.3390/pr3010046
Received: 15 December 2014 / Accepted: 23 December 2014 / Published: 12 January 2015
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Abstract
Tissue engineering and, more broadly, regenerative medicine is moving into a phase where we are seeing potential therapies moving ‘slowly but surely’ from the laboratory into the clinic, i.e., from research to the clinic and into manufacturing. The numbers of cells required
[...] Read more.
Tissue engineering and, more broadly, regenerative medicine is moving into a phase where we are seeing potential therapies moving ‘slowly but surely’ from the laboratory into the clinic, i.e., from research to the clinic and into manufacturing. The numbers of cells required for cell therapy protocols can vary from tens of millions, to billions [1], and it is widely considered that such cell numbers can be produced in bioreactor systems. Thus, the bioreactor is becoming a key tool for culturing clinical numbers of human cells and the regenerative medicine industry will become increasingly reliant on such systems at the centre of cell therapy production and tissue engineering.[...] Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)

Research

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Open AccessArticle Experimental Characterisation of Fluid Mechanics in a Spinner Flask Bioreactor
Processes 2014, 2(4), 753-772; doi:10.3390/pr2040753
Received: 28 July 2014 / Revised: 1 September 2014 / Accepted: 30 September 2014 / Published: 17 October 2014
Cited by 3 | PDF Full-text (10437 KB) | HTML Full-text | XML Full-text
Abstract
The spinner flask bioreactor has been widely used in in vitro cell culturing processes due to its superiority in providing a homogeneous culture environment compared to traditional culturing methods. However, there is limited understanding of the flow fields in these bioreactors, and optimum
[...] Read more.
The spinner flask bioreactor has been widely used in in vitro cell culturing processes due to its superiority in providing a homogeneous culture environment compared to traditional culturing methods. However, there is limited understanding of the flow fields in these bioreactors, and optimum culture conditions are yet to be determined. This article presents the experimental characterization of the flow field within a spinner flask at varying speeds (10 RPM to 80 RPM) and impeller positions. An optical, non-invasive measurement technique, Particle Image Velocimetry (PIV), was employed to illustrate the fluid flow and calculate the stresses and vorticity associated with the flow within the flask. The largest recirculation structure was observed in the meridional plane at the highest impeller position while the highest shear stress region was observed at the base of the spinner flask. The study provides an overview of the fluid structure within the spinner flask in the meridional and azimuthal planes. Furthermore, the results presented in this study give an accurate quantification of the range of stresses for the given impeller speeds. These results provide estimates of the biomechanical properties within the type of spinner flask used in many published cell studies. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessArticle A Novel Through-Thickness Perfusion Bioreactor for the Generation of Scaffold-Free Tissue Engineered Cartilage
Processes 2014, 2(3), 658-674; doi:10.3390/pr2030658
Received: 16 February 2014 / Revised: 2 May 2014 / Accepted: 30 July 2014 / Published: 13 August 2014
Cited by 4 | PDF Full-text (2598 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to characterize our designed through-thickness perfusion bioreactor which could generate large scaffold-free tissue engineered cartilage constructs. The hypothesis being that through-thickness perfusion could accelerate maturation of scaffold-free tissue engineered cartilage, grown in transwell culture inserts large enough
[...] Read more.
The objective of this study was to characterize our designed through-thickness perfusion bioreactor which could generate large scaffold-free tissue engineered cartilage constructs. The hypothesis being that through-thickness perfusion could accelerate maturation of scaffold-free tissue engineered cartilage, grown in transwell culture inserts large enough to repair typical size chondral lesions in the human knee. Internal cell culture media temperature and pH were examined over time, upon implementation of the bioreactor perfusion system inside a CO2 incubator, to ensure adequate regulation conducive to cell viability. Results indicate that temperature and pH both equilibrate within approximately 3 h. The bioreactor was tested for its efficacy to support formation of 4.5 cm2 constructs by porcine neonatal chondrocytes. Tests were conducted under three conditions: immediate perfusion with flow from bottom to top, immediate perfusion with media flow from top to bottom, and bottom to top perfusion after four weeks of static culture, giving the cells time to self-aggregate into a consolidated construct prior to perfusion. The best cell culture results were obtained when perfusion was delayed for four weeks relative to the immediate perfusion of the other methods, and this should be further investigated. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
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Open AccessArticle Analysis of Gene Expression Signatures for Osteogenic 3D Perfusion-Bioreactor Cell Cultures Based on a Multifactorial DoE Approach
Processes 2014, 2(3), 639-657; doi:10.3390/pr2030639
Received: 14 February 2014 / Revised: 9 May 2014 / Accepted: 9 July 2014 / Published: 8 August 2014
Cited by 1 | PDF Full-text (1240 KB) | HTML Full-text | XML Full-text
Abstract
The use of multifactorial design of experiments (DoE) in tissue engineering bioprocess development will contribute to the robust manufacturing of tissue engineered constructs by linking their quality characteristics to bioprocess operating parameters. In this work, perfusion bioreactors were used for the in vitro
[...] Read more.
The use of multifactorial design of experiments (DoE) in tissue engineering bioprocess development will contribute to the robust manufacturing of tissue engineered constructs by linking their quality characteristics to bioprocess operating parameters. In this work, perfusion bioreactors were used for the in vitro culture and osteogenic differentiation of human periosteum-derived cells (hPDCs) seeded on three-dimensional titanium (Ti) alloy scaffolds. A CaP-supplemented medium was used to induce differentiation of the cultured hPDCs. A two-level, three-factor fractional factorial design was employed to evaluate a range of bioreactor operating conditions by changing the levels of the following parameters: flow rate (0.5–2 mL/min), cell culture duration (7–21 days) and cell seeding density (1.5 × 103–3 × 103 cells/cm2). This approach allowed for evaluating the individual impact of the aforementioned process parameters upon a range of genes that are related to the osteogenic lineage, such as collagen type I, alkaline phosphatase, osterix, osteopontin and osteocalcin. Furthermore, by overlaying gene-specific response surfaces, an integrated operating process space was highlighted within which predetermined values of the six genes of interest (i.e., gene signature) could be minimally met over the course of the bioreactor culture time. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessArticle A Novel Seeding and Conditioning Bioreactor for Vascular Tissue Engineering
Processes 2014, 2(3), 526-547; doi:10.3390/pr2030526
Received: 10 February 2014 / Revised: 21 May 2014 / Accepted: 20 June 2014 / Published: 8 July 2014
Cited by 1 | PDF Full-text (11168 KB) | HTML Full-text | XML Full-text
Abstract
Multiple efforts have been made to develop small-diameter tissue engineered vascular grafts using a great variety of bioreactor systems at different steps of processing. Nevertheless, there is still an extensive need for a compact all-in-one system providing multiple and simultaneous processing. The aim
[...] Read more.
Multiple efforts have been made to develop small-diameter tissue engineered vascular grafts using a great variety of bioreactor systems at different steps of processing. Nevertheless, there is still an extensive need for a compact all-in-one system providing multiple and simultaneous processing. The aim of this project was to develop a new device to fulfill the major requirements of an ideal system that allows simultaneous seeding, conditioning, and perfusion. The newly developed system can be actuated in a common incubator and consists of six components: a rotating cylinder, a pump, a pulse generator, a control unit, a mixer, and a reservoir. Components that are in direct contact with cell media, cells, and/or tissue allow sterile processing. Proof-of-concept experiments were performed with polyurethane tubes and collagen tubes. The scaffolds were seeded with fibroblasts and endothelial cells that were isolated from human saphenous vein segments. Scanning electron microscopy and immunohistochemistry showed better seeding success of polyurethane scaffolds in comparison to collagen. Conditioning of polyurethane tubes with 100 dyn/cm2 resulted in cell detachments, whereas a moderate conditioning program with stepwise increase of shear stress from 10 to 40 dyn/cm2 induced a stable and confluent cell layer. The new bioreactor is a powerful tool for quick and easy testing of various scaffold materials for the development of tissue engineered vascular grafts. The combination of this bioreactor with native tissue allows testing of medical devices and medicinal substances under physiological conditions that is a good step towards reduction of animal testing. In the long run, the bioreactor could turn out to produce tissue engineered vascular grafts for human applications “at the bedside”. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessArticle A Novel Cell Seeding Chamber for Tissue Engineering and Regenerative Medicine
Processes 2014, 2(2), 361-370; doi:10.3390/pr2020361
Received: 14 February 2014 / Revised: 11 April 2014 / Accepted: 18 April 2014 / Published: 30 April 2014
Cited by 1 | PDF Full-text (605 KB) | HTML Full-text | XML Full-text
Abstract
There is an increasing demand for bone graft substitutes that are used as osteoconductive scaffolds in the treatment of bone defects and fractures. Achieving optimal bone regeneration requires initial cell seeding of the scaffolds prior to implantation. In order to achieve an efficient
[...] Read more.
There is an increasing demand for bone graft substitutes that are used as osteoconductive scaffolds in the treatment of bone defects and fractures. Achieving optimal bone regeneration requires initial cell seeding of the scaffolds prior to implantation. In order to achieve an efficient seeding of the scaffolds, a novel cell seeding chamber was developed. The cell seeding chamber is a closed assembly that works like an hourglass. The position of the scaffold is between two reservoirs containing the cell suspension (e.g., blood or autologous bone marrow). The cell suspension at the upper reservoir flows through the scaffold by gravitational force. The cell suspension is collected at the lower reservoir. When the upper reservoir is empty the whole assembly is turned and the process starts again. In this study, a new compact cell seeding chamber for initial cell seeding has been developed that can be used in situ. The basic functionality of the cell seeding chamber was demonstrated with a blood substitute. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessArticle Design and Validation of a Cyclic Strain Bioreactor to Condition Spatially-Selective Scaffolds in Dual Strain Regimes
Processes 2014, 2(2), 345-360; doi:10.3390/pr2020345
Received: 22 November 2013 / Revised: 31 January 2014 / Accepted: 21 February 2014 / Published: 31 March 2014
Cited by 1 | PDF Full-text (777 KB) | HTML Full-text | XML Full-text
Abstract
The objective of this study was to design and validate a unique bioreactor design for applying spatially selective, linear, cyclic strain to degradable and non-degradable polymeric fabric scaffolds. This system uses a novel three-clamp design to apply cyclic strain via a computer controlled
[...] Read more.
The objective of this study was to design and validate a unique bioreactor design for applying spatially selective, linear, cyclic strain to degradable and non-degradable polymeric fabric scaffolds. This system uses a novel three-clamp design to apply cyclic strain via a computer controlled linear actuator to a specified zone of a scaffold while isolating the remainder of the scaffold from strain. Image analysis of polyethylene terephthalate (PET) woven scaffolds subjected to a 3% mechanical stretch demonstrated that the stretched portion of the scaffold experienced 2.97% ± 0.13% strain (mean ± standard deviation) while the unstretched portion experienced 0.02% ± 0.18% strain. NIH-3T3 fibroblast cells were cultured on the PET scaffolds and half of each scaffold was stretched 5% at 0.5 Hz for one hour per day for 14 days in the bioreactor. Cells were checked for viability and proliferation at the end of the 14 day period and levels of glycosaminoglycan (GAG) and collagen (hydroxyproline) were measured as indicators of extracellular matrix production. Scaffolds in the bioreactor showed a seven-fold increase in cell number over scaffolds cultured statically in tissue culture plastic petri dishes (control). Bioreactor scaffolds showed a lower concentration of GAG deposition per cell as compared to the control scaffolds largely due to the great increase in cell number. A 75% increase in hydroxyproline concentration per cell was seen in the bioreactor stretched scaffolds as compared to the control scaffolds. Surprisingly, little differences were experienced between the stretched and unstretched portions of the scaffolds for this study. This was largely attributed to the conditioned and shared media effect. Results indicate that the bioreactor system is capable of applying spatially-selective, linear, cyclic strain to cells growing on polymeric fabric scaffolds and evaluating the cellular and matrix responses to the applied strains. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessArticle Towards a Tissue-Engineered Ligament: Design and Preliminary Evaluation of a Dedicated Multi-Chamber Tension-Torsion Bioreactor
Processes 2014, 2(1), 167-179; doi:10.3390/pr2010167
Received: 3 January 2014 / Revised: 7 February 2014 / Accepted: 10 February 2014 / Published: 19 February 2014
Cited by 4 | PDF Full-text (1439 KB) | HTML Full-text | XML Full-text
Abstract
Tissue engineering may constitute a promising alternative to current strategies in ligament repair, providing that suitable scaffolds and culture conditions are proposed. The objective of the present contribution is to present the design and instrumentation of a novel multi-chamber tension-torsion bioreactor dedicated to
[...] Read more.
Tissue engineering may constitute a promising alternative to current strategies in ligament repair, providing that suitable scaffolds and culture conditions are proposed. The objective of the present contribution is to present the design and instrumentation of a novel multi-chamber tension-torsion bioreactor dedicated to ligament tissue engineering. A preliminary biological evaluation of a new braided scaffold within this bioreactor under dynamic loading is reported, starting with the development of a dedicated seeding protocol validated from static cultures. The results of these preliminary biological characterizations confirm that the present combination of scaffold, seeding protocol and bioreactor may enable us to head towards a suitable ligament tissue-engineered construct. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessArticle A Multiwell Disc Appliance Used to Deliver Quantifiable Accelerations and Shear Stresses at Sonic Frequencies
Processes 2014, 2(1), 71-88; doi:10.3390/pr2010071
Received: 13 September 2013 / Revised: 25 November 2013 / Accepted: 20 December 2013 / Published: 10 January 2014
Cited by 3 | PDF Full-text (495 KB) | HTML Full-text | XML Full-text
Abstract
To mimic in vivo vibration of vocal fold cells, we studied the controllability and range of frequency, acceleration, duration, and shear stress in a new bioreactor attachment. The custom multiwell disc appliance fits into a commercially built rheometer, together termed a torsional rheometer
[...] Read more.
To mimic in vivo vibration of vocal fold cells, we studied the controllability and range of frequency, acceleration, duration, and shear stress in a new bioreactor attachment. The custom multiwell disc appliance fits into a commercially built rheometer, together termed a torsional rheometer bioreactor (TRB). Previous attachments to the TRB were capable of 50–100 Hz vibrations at relatively high strains but were limited to single-sample experiments. The TRB-multiwell disc system accommodates 20 samples in partially fluid-filled wells in an aseptic environment delivering three different acceleration conditions to different samples simultaneously. Frequency and amplitude used to calculate acceleration along with duration and shear stress were controllable and quantifiable using a combination of built-in rheometer sensors, manufacturer software, and smooth particle hydrodynamics (SPH) simulations. Computed shear stresses at the well bottom using SPH in two and three dimensions were verified with analytical approximations. Results demonstrate capabilities of the TRB-multiwell disc system that, when combined with computational modeling, provide quantifiable vibration parameters covering frequencies 0.01–250 Hz, accelerations of 0.02–300 m/s2, and shear stresses of 0.01–1.4 Pa. It is well-suited for studying cell function underlying vocal fold lamina propria homeostasis, inflammation, and wound healing under differential vibration conditions. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
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Open AccessArticle Model-Based Optimization of Scaffold Geometry and Operating Conditions of Radial Flow Packed-Bed Bioreactors for Therapeutic Applications
Processes 2014, 2(1), 34-57; doi:10.3390/pr2010034
Received: 18 September 2013 / Revised: 5 December 2013 / Accepted: 19 December 2013 / Published: 3 January 2014
Cited by 4 | PDF Full-text (1625 KB) | HTML Full-text | XML Full-text
Abstract
Radial flow perfusion of cell-seeded hollow cylindrical porous scaffolds may overcome the transport limitations of pure diffusion and direct axial perfusion in the realization of bioengineered substitutes of failing or missing tissues. Little has been reported on the optimization criteria of such bioreactors.
[...] Read more.
Radial flow perfusion of cell-seeded hollow cylindrical porous scaffolds may overcome the transport limitations of pure diffusion and direct axial perfusion in the realization of bioengineered substitutes of failing or missing tissues. Little has been reported on the optimization criteria of such bioreactors. A steady-state model was developed, combining convective and dispersive transport of dissolved oxygen with Michaelis-Menten cellular consumption kinetics. Dimensional analysis was used to combine more effectively geometric and operational variables in the dimensionless groups determining bioreactor performance. The effectiveness of cell oxygenation was expressed in terms of non-hypoxic fractional construct volume. The model permits the optimization of the geometry of hollow cylindrical constructs, and direction and magnitude of perfusion flow, to ensure cell oxygenation and culture at controlled oxygen concentration profiles. This may help engineer tissues suitable for therapeutic and drug screening purposes. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
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Open AccessArticle In Vitro Assessment of Migratory Behavior of Two Cell Populations in a Simple Multichannel Microdevice
Processes 2013, 1(3), 349-359; doi:10.3390/pr1030349
Received: 22 July 2013 / Revised: 17 October 2013 / Accepted: 20 November 2013 / Published: 18 December 2013
Cited by 1 | PDF Full-text (1412 KB) | HTML Full-text | XML Full-text
Abstract
Recent literature suggests that mesenchymal stem/stromal cells (MSC) could be used as Trojan Horses to deliver “death-signals” to cancer cells. Herein, we describe the development of a novel multichannel cell migration device, and use it to investigate the relative migration rates of bone
[...] Read more.
Recent literature suggests that mesenchymal stem/stromal cells (MSC) could be used as Trojan Horses to deliver “death-signals” to cancer cells. Herein, we describe the development of a novel multichannel cell migration device, and use it to investigate the relative migration rates of bone marrow-derived MSC and breast cancer cells (MCF-7) towards each other. Confluent monolayers of MSC and MCF-7 were established in adjacent chambers separated by an array of 14 microchannels. Initially, culture chambers were isolated by air bubbles (air-valves) contained within each microchannel, and then bubbles were displaced to initiate the assay. The MCF-7 cells migrated preferentially towards MSC, whilst the MSC did not migrate preferentially towards the MCF-7 cells. Our results corroborate previous literature that suggests MSC migration towards cancer cells in vivo is in response to the associated inflammation rather than directly to signals secreted by the cancer cells themselves. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
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Review

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Open AccessReview Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors
Processes 2014, 2(3), 548-569; doi:10.3390/pr2030548
Received: 21 May 2014 / Revised: 17 June 2014 / Accepted: 2 July 2014 / Published: 25 July 2014
Cited by 5 | PDF Full-text (4367 KB) | HTML Full-text | XML Full-text
Abstract
In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro- and milli-fluidic geometries are first used to illustrate the concepts, followed by
[...] Read more.
In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro- and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
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Open AccessReview Bioreactor Systems for Human Bone Tissue Engineering
Processes 2014, 2(2), 494-525; doi:10.3390/pr2020494
Received: 24 February 2014 / Revised: 19 April 2014 / Accepted: 24 April 2014 / Published: 11 June 2014
Cited by 6 | PDF Full-text (2334 KB) | HTML Full-text | XML Full-text
Abstract
Critical size skeletal defects resulting from trauma and pathological disorders still remain a major clinical problem worldwide. Bone engineering aims at generating unlimited amounts of viable tissue substitutes by interfacing osteocompetent cells of different origin and developmental stage with compliant biomaterial scaffolds, and
[...] Read more.
Critical size skeletal defects resulting from trauma and pathological disorders still remain a major clinical problem worldwide. Bone engineering aims at generating unlimited amounts of viable tissue substitutes by interfacing osteocompetent cells of different origin and developmental stage with compliant biomaterial scaffolds, and culture the cell/scaffold constructs under proper culture conditions in bioreactor systems. Bioreactors help supporting efficient nutrition of cultured cells and allow the controlled provision of biochemical and biophysical stimuli required for functional regeneration and production of clinically relevant bone grafts. In this review, the authors report the advances in the development of bone tissue substitutes using human cells and bioreactor systems. Principal types of bioreactors are reviewed, including rotating wall vessels, spinner flasks, direct and indirect flow perfusion bioreactors, as well as compression systems. Specifically, the review deals with: (i) key elements of bioreactor design; (ii) range of values of stress imparted to cells and physiological relevance; (iii) maximal volume of engineered bone substitutes cultured in different bioreactors; and (iv) experimental outcomes and perspectives for future clinical translation. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
Open AccessReview Evaluation of Diffusive Transport and Cellular Uptake of Nutrients in Tissue Engineered Constructs Using a Hybrid Discrete Mathematical Model
Processes 2014, 2(2), 333-344; doi:10.3390/pr2020333
Received: 10 December 2013 / Revised: 20 February 2014 / Accepted: 28 February 2014 / Published: 28 March 2014
Cited by 1 | PDF Full-text (849 KB) | HTML Full-text | XML Full-text
Abstract
Tissue engineering systems for orthopedic tissues, such as articular cartilage, are often based on the use of biomaterial scaffolds that are seeded with cells and supplied with nutrients or growth factors. In such systems, relationships between the functional outcomes of the engineered tissue
[...] Read more.
Tissue engineering systems for orthopedic tissues, such as articular cartilage, are often based on the use of biomaterial scaffolds that are seeded with cells and supplied with nutrients or growth factors. In such systems, relationships between the functional outcomes of the engineered tissue construct and aspects of the initial system design are not well known, suggesting the use of mathematical models as an additional tool for optimal system design. This study develops a reaction-diffusion model that quantitatively describes the competing effects of nutrient diffusion and the cellular uptake of nutrients in a closed bioreactor system consisting of a cell-seeded scaffold adjacent to a nutrient-rich bath. An off-lattice hybrid discrete modeling framework is employed in which the diffusion equation incorporates a loss term that accounts for absorption due to nutrient uptake by cells that are modeled individually. Numerical solutions are developed based on a discontinuous Galerkin finite element method with high order quadrature to accurately resolve fine-scale cellular effects. The resulting model is applied to demonstrate that the ability of cells to absorb nutrients over time is highly dependent on both the normal distance to the nutrient bath, as well as the nutrient uptake rate for individual cells. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)

Other

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Open AccessTechnical Note Design and Validation of a Physiologically-Adapted Bioreactor for Tissue Engineering of the Nucleus Pulposus
Processes 2014, 2(1), 1-11; doi:10.3390/pr2010001
Received: 30 September 2013 / Revised: 20 November 2013 / Accepted: 12 December 2013 / Published: 20 December 2013
Cited by 3 | PDF Full-text (449 KB) | HTML Full-text | XML Full-text
Abstract
A novel multi-axial bioreactor was designed and developed to deliver combinations of the following dynamic mechanical stimulation conditions: hydrostatic pressure, pulsatile perfusion flow and uniaxial compression in order to mimic in vivo conditions. This mechanical arrangement simultaneously allows triaxial stimulation and characterization of
[...] Read more.
A novel multi-axial bioreactor was designed and developed to deliver combinations of the following dynamic mechanical stimulation conditions: hydrostatic pressure, pulsatile perfusion flow and uniaxial compression in order to mimic in vivo conditions. This mechanical arrangement simultaneously allows triaxial stimulation and characterization of mechanical properties of samples, in particular simulating the conditions experienced by the nucleus pulposus in vivo. A series of initial experiments were performed on this prototype system using consistent, commercially-available, three dimensional scaffolds in combination with human dermal fibroblasts. Our results show that while such bioreactors hold much promise in tissue engineering of desired organs, achieving the right combination of mechanical stimuli and other conditions required in order to enhance the final properties of the cell-scaffold systems is challenging. Full article
(This article belongs to the Special Issue Design of Bioreactor Systems for Tissue Engineering)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.


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