Processes2014, 2(3), 548-569; doi:10.3390/pr2030548 - published online 25 July 2014 Show/Hide Abstract
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 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.
Processes2014, 2(3), 526-547; doi:10.3390/pr2030526 - published online 8 July 2014 Show/Hide Abstract
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 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”.
Processes2014, 2(2), 494-525; doi:10.3390/pr2020494 - published online 11 June 2014 Show/Hide Abstract
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 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.
Processes2014, 2(2), 466-493; doi:10.3390/pr2020466 - published online 5 June 2014 Show/Hide Abstract
Abstract: The seminal work of Michael Faraday in 1850s transmuted the “Alchemy of gold” into a fascinating scientific endeavor over the millennia, particularly in the past half century. Gold nanoparticles (GNPs) arguably hold the central position of nanosciences due to their intriguing size-and-shape dependent physicochemical properties, non-toxicity, and ease of functionalization and potential for wide range of applications. The core chemistry involved in the syntheses is essentially not very different from what Michael Faraday resorted to: transforming ions into metallic gold using mild reducing agents. However, the process of such reduction and outcome (shapes and sizes) are intricately dependent on basic operational parameters such as sequence of addition and efficiency of mixing of the reagents. Hence, irreproducibility in synthesis and maintaining batch-to-batch quality are major obstacles in this seemingly straightforward process, which poses challenges in scaling-up. Microreactors, by the virtue of excellent control over reagent mixing in space and time within narrow channel networks, opened a new horizon of possibilities to tackle such problems to produce GNPs in more reliable, reproducible and scalable ways. In this review, we will delineate the state-of-the-art of GNPs synthesis using microreactors and will discuss in length how such “flask-to-chip” paradigm shift may revolutionize the very concept of nanosyntheses.
Processes2014, 2(2), 441-465; doi:10.3390/pr2020441 - published online 27 May 2014 Show/Hide Abstract
Abstract: State-of-the-art techniques for the fabrication of compound semiconductors are mostly vacuum-based physical vapor or chemical vapor deposition processes. These vacuum-based techniques typically operate at high temperatures and normally require higher capital costs. Solution-based techniques offer opportunities to fabricate compound semiconductors at lower temperatures and lower capital costs. Among many solution-based deposition processes, chemical bath deposition is an attractive technique for depositing semiconductor films, owing to its low temperature, low cost and large area deposition capability. Chemical bath deposition processes are mainly performed using batch reactors, where all reactants are fed into the reactor simultaneously and products are removed after the processing is finished. Consequently, reaction selectivity is difficult, which can lead to unwanted secondary reactions. Microreactor-assisted solution deposition processes can overcome this limitation by producing short-life molecular intermediates used for heterogeneous thin film synthesis and quenching the reaction prior to homogeneous reactions. In this paper, we present progress in the synthesis and deposition of semiconductor thin films with a focus on CdS using microreactor-assisted solution deposition and provide an overview of its prospect for scale-up.
Processes2014, 2(2), 419-440; doi:10.3390/pr2020419 - published online 27 May 2014 Show/Hide Abstract
Abstract: Many researchers have studied the biosorption of different pollutants. However, a quite limited number of works focus on selectivity, which may be characterized as specific property for each biosorbent. Two main criteria need to be adopted for the selection and synthesis of modern biosorbents, such as their rebinding capacity and selectivity for only one target, molecule, ion, etc. Selective biosorption could be achieved using in synthesis an innovative technique termed molecular imprinting; the idea applied through specific polymers (Molecular Imprinted Polymers (MIPs)) was used in many fields, mainly analytical. In the present work, also isotherm and kinetic models were reviewed highlighting some crucial parameters, which possibly affect selectivity. A critical analysis of the biosorption insights for biosorbents, mostly selective, describes their characteristics, advantages and limitations, and discusses various bioengineering mechanisms involved.