Bioengineering, Volume 4, Issue 4 (December 2017) – 18 articles

Previous studies have established halloysite nanotubes (HNTs) as viable nanocontainers capable of sustained release of a variety of antibiotics, corrosion agents, chemotherapeutics and growth factors either from their lumen or in outer surface coatings. Accordingly, halloysite nanotubes (HNTs) hold great promise as drug delivery carriers in the fields of pharmaceutical science and regenerative medicine. This study explored the potential of 3D printing drug doped HNT constructs. We used a model drug, gentamicin (GS) and polylactic acid (PLA) to fabricate GS releasing disks, beads, and pellets. Gentamicin was released from 3D printed constructs in a sustained manner and had a superior anti-bacterial growth inhibition effect that was dependent on GS doping concentration. While this study focused on a model drug, gentamicin, combination therapy is possible through the fabrication of medical devices containing HNTs doped with a suite of antibiotics or antifungals. Furthermore, tailored dosage levels, suites of antimicrobials, delivered locally would reduce the toxicity of individual agents, prevent the emergence of resistant strains, and enable the treatment of mixed infections. Full article

Hinge-based Ankle Foot Orthosis (HAFO) is one of the most common non-surgical solutions for the foot drop. In conventional HAFOs, the ankle joint is almost locked, and plantar flexion is restricted due to the high stiffness of the hinge mechanism. This often leads to a rigid walking gate cycle, poor muscle activity, and muscle atrophy. Since the ankle torque-angle loop has a non-linear profile, the use of a superelastic NiTi spring within the hinge, due to its nonlinear behavior, could recreate a close-to-normal stiffness of the normal ankle joint, which, in turn, could create a more natural walk. The focus of this study is to evaluate the performance of a superelastic NiTi spring versus a conventional Stainless Steel spring in a hinge mechanism of a custom-fit HAFO. To this aim, a custom-fit HAFO was fabricated via the fast casting technique. Then, motion analysis was performed for two healthy subjects (Case I and Case II): (i) subjects with bare foot; (ii) subjects wearing a conventional HAFO with no spring; (iii) subjects wearing a conventional Stainless Steel-based HAFO; and (iv) subjects wearing a NiTi spring-based HAFO. The data related to the ankle angle and the amount of moment applied to the ankle during walking were recorded using Cortex software and used for the evaluations. Finally, Finite Element Analysis (FEA) was performed to evaluate the safety of the designed HAFO. The NiTi spring offers a higher range of motion (7.9 versus 4.14 degree) and an increased level of moment (0.55 versus 0.36 N·m/kg). Furthermore, a NiTi spring offers an ankle torque-angle loop closer to that of the healthy subjects. Full article

Moving towards a bio-based and circular economy implies a major focus on the responsible and sustainable utilization of bio-resources. The emergence of nanotechnology has opened multiple possibilities, not only in the existing industrial sectors, but also for completely novel applications of nanoscale bio-materials, the commercial exploitation of which has only begun during the last few years. Bio-based materials are often assumed not to be toxic. However, this pre-assumption is not necessarily true. Here, we provide a short overview on health and environmental aspects associated with bio-based nanomaterials, and on the relevant regulatory requirements. We also discuss testing strategies that may be used for screening purposes at pre-commercial stages. Although the tests presently used to reveal hazards are still evolving, regarding modifi­cations required for nanomaterials, their application is needed before the upscaling or commercialization of bio-based nanomaterials, to ensure the market potential of the nanomaterials is not delayed by uncertainties about safety issues. Full article

The effect of the addition of two [4-butyltrimethylammonium]-xylan chloride polyelectrolytes (BTMAXs) on bacterial cellulose (BC) was evaluated. The first strategy was to add the polyelectrolytes to the culture medium together with a cell suspension of the bacterium. After one week of cultivation, the films were collected and purified. The second approach consisted of obtaining a purified and homogenized BC, to which the polyelectrolytes were added subsequently. The films were characterized in terms of tear and burst indexes, optical properties, surface free energy, static contact angle, Gurley porosity, SEM, X-ray diffraction and AFM. Although there are small differences in mechanical and optical properties between the nanocomposites and control films, the films obtained by BC synthesis in the presence of BTMAXs were remarkably less opaque, rougher, and had a much lower specular gloss. The surface free energy depends on the BTMAXs addition method. The crystallinity of the composites is lower than that of the control material, with a higher reduction of this parameter in the composites obtained by adding the BTMAXs to the culture medium. In view of these results, it can be concluded that BC–BTMAX composites are a promising new material, for example, for paper restoration. Full article

A techno-economic evaluation of bioenergy production from macroalgae was carried out in this study. Six different scenarios were examined for the production of different energy products and by-products. Seaweed was produced either via the longline method or the grid method. Final products of these scenarios were either ethanol from fermentation, or electricity from anaerobic digestion (AD). By-products were digestate for AD, and animal feed, or electricity and digestate, for the fermentation pathway. Bioenergy breakeven selling prices were investigated according to the cost components and the feedstock supply chain, while suggestions for potential optimization of costs were provided. The lowest production level of dry seaweed to meet 0.93 ($/L) for ethanol fuel and 0.07 $/kW-h for electricity was found to be 0.68 and 3.7 million tonnes (dry basis), respectively. At the moment, biofuel production from seaweed has been determined not to be economically feasible, but achieving economic production may be possible by lowering production costs and increasing the area under cultivation. Full article

Thermoplastic composite materials containing wood fibers are gaining increasing interest in the manufacturing industry. One approach is to use nano- or micro-size cellulosic fibrils as additives and to improve the mechanical properties obtainable with only small fibril loadings by exploiting the high aspect ratio and surface area of nanocellulose. In this study, we used four different wood cellulose-based materials in a thermoplastic polylactide (PLA) matrix: cellulose nanofibrils produced from softwood kraft pulp (CNF) and dissolving pulp (CNFSD), enzymatically prepared high-consistency nanocellulose (HefCel) and microcellulose (MC) together with long alkyl chain dispersion-improving agents. We observed increased impact strength with HefCel and MC addition of 5% and increased tensile strength with CNF addition of 3%. The addition of a reactive dispersion agent, epoxy-modified linseed oil, was found to be favorable in combination with HefCel and MC. Full article

Determining the impact of inter-subject variability on airflow pattern and nanoparticle deposition in the human respiratory system is necessary to generate population-representative models, useful for several biomedical engineering applications. Thus, the overall research objective is to quantitatively correlate geometric parameters and coupled transport characteristics of air, vapor, and nanoparticles. Focusing on identifying morphological parameters that significantly influence airflow field and nanoparticle transport, an experimentally validated computational fluid-particle dynamics (CFPD) model was employed to simulate airflow pattern in three human lung-airway configurations. The numerical results will be used to generate guidelines to construct a representative geometry of the human respiratory system. Full article

The rise in popularity of the Paralympics in recent years has created a need for effective, low-cost sports-prosthetic devices for upper-limb amputees. There are various opportunities for lower-limb amputees to participate in cycling; however, there are only few options for those with upper-limb amputations. If the individual previously participated in cycling, a cycling-specific prosthesis could allow these activities to be integrated into rehabilitation methods. This article describes the processes involved with designing, developing and manufacturing such a prosthesis. The fundamental needs of people with upper-limb amputation were assessed and realised in the prototype of a transradial terminal device with two release mechanisms, including a sliding mechanism (for falls and minor collisions) and clamping mechanism (for head-on collisions). The sliding mechanism requires the rider to exert approximately 200 N, while the clamping mechanism requires about 700 N. The force ranges can be customised to match rider requirements. Experiments were conducted in a controlled environment to demonstrate stability of the device during normal cycling. Moreover, a volunteer test-rider was able to successfully activate the release mechanism during a simulated emergency scenario. The development of this prosthesis has the potential to enable traumatic upper-limb amputees to participate in cycling for rehabilitation or recreation. Full article

This editorial paper provides a synopsis of the contributions to the Bioengineering special issue “Advances in Polyhydroxyalkanoate (PHA) Production”. It illustrates the embedding of the issue’s individual research articles in the current global research and development landscape related to polyhydroxyalkanoates (PHA). The article shows how these articles are interrelated to each other, reflecting the entire PHA process chain including strain selection, metabolic and genetic considerations, feedstock evaluation, fermentation regimes, process engineering, and polymer processing towards high-value marketable products. Full article

Camellia (genus of flowering plants of fam. Theaceae) is one of the main crops in Asia, where tea and oil from leaves and seeds have been utilized for thousands of years. This plant is excellently adapted to the climate and soil of Galicia (northwestern Spain) and northern Portugal where it is grown not only as an ornamental plant, but to be evaluated as a source of bioactive compounds. In this work, the main fatty acids were extracted from Camellia seeds of four varieties of Camellia: sasanqua, reticulata, japonica and sinensis, by means of matrix-solid phase dispersion (MSPD), and analyzed by gas chromatography (GC) with MS detection of the corresponding methyl esters. MSPD constitutes an efficient and greener alternative to conventional extraction techniques, moreover if it is combined with the use of green solvents such as limonene. The optimization of the MSPD extraction procedure has been conducted using a multivariate approach based on strategies of experimental design, which enabled the simultaneous evaluation of the factors influencing the extraction efficiency as well as interactions between factors. The optimized method was applied to characterize the fatty acids profiles of four Camellia varieties seeds, allowing us to compare their fatty acid composition. Full article

During the regulatory requested process validation of pharmaceutical manufacturing processes, companies aim to identify, control, and continuously monitor process variation and its impact on critical quality attributes (CQAs) of the final product. It is difficult to directly connect the impact of single process parameters (PPs) to final product CQAs, especially in biopharmaceutical process development and production, where multiple unit operations are stacked together and interact with each other. Therefore, we want to present the application of Monte Carlo (MC) simulation using an integrated process model (IPM) that enables estimation of process capability even in early stages of process validation. Once the IPM is established, its capability in risk and criticality assessment is furthermore demonstrated. IPMs can be used to enable holistic production control strategies that take interactions of process parameters of multiple unit operations into account. Moreover, IPMs can be trained with development data, refined with qualification runs, and maintained with routine manufacturing data which underlines the lifecycle concept. These applications will be shown by means of a process characterization study recently conducted at a world-leading contract manufacturing organization (CMO). The new IPM methodology therefore allows anticipation of out of specification (OOS) events, identify critical process parameters, and take risk-based decisions on counteractions that increase process robustness and decrease the likelihood of OOS events. Full article

Identification of critical process parameters that impact product quality is a central task during regulatory requested process validation. Commonly, this is done via design of experiments and identification of parameters significantly impacting product quality (rejection of the null hypothesis that the effect equals 0). However, parameters which show a large uncertainty and might result in an undesirable product quality limit critical to the product, may be missed. This might occur during the evaluation of experiments since residual/un-modelled variance in the experiments is larger than expected a priori. Estimation of such a risk is the task of the presented novel retrospective power analysis permutation test. This is evaluated using a data set for two unit operations established during characterization of a biopharmaceutical process in industry. The results show that, for one unit operation, the observed variance in the experiments is much larger than expected a priori, resulting in low power levels for all non-significant parameters. Moreover, we present a workflow of how to mitigate the risk associated with overlooked parameter effects. This enables a statistically sound identification of critical process parameters. The developed workflow will substantially support industry in delivering constant product quality, reduce process variance and increase patient safety. Full article

Ion pair amphiphile (IPA), a lipid-like complex composed of a pair of cationic and anionic surfactants, has great potentials in various pharmaceutical applications. In this work, we utilized molecular dynamics (MD) simulation to systematically examine the structural and mechanical properties of the biomimetic bilayers consist of alkyltrimethyl-ammonium-alkylsulfate (C_mTMA⁺-C_nS⁻) IPAs with various alkyl chain combinations. Our simulations show an intrinsic one-atom offset for the C_mTMA⁺ and C_nS⁻ alignment, leading to the asymmetric index definition of ΔC = m − (n + 1). Larger |ΔC| gives rise to higher conformational fluctuations of the alkyl chains with the reduced packing order and mechanical strength. In contrast, increasing the IPA chain length enhances the van der Waals interactions within the bilayer and thus improves the bilayer packing order and mechanical properties. Further elongating the C_mTMA⁺-C_nS⁻ alkyl chains to m and n ≥ 12 causes the liquid disorder to gel phase transition of the bilayer at 298 K, with the threshold membrane properties of 0.45 nm² molecular area, deuterium order parameter value of 0.31, and effective bending rigidity of 20 k_BT, etc. The combined results provide molecular insights into the design of biomimetic IPA bilayers with wide structural and mechanical characteristics for various applications. Full article

Soybean oil production is the basic process for soybean applications. Cash flow analysis is used to estimate the profitability of a manufacturing venture. Besides capital investments, operating costs, and revenues, the interest rate is the factor to estimate the net present value (NPV), break-even points, and payback time; which are benchmarks for profitability evaluation. The positive NPV and reasonable payback time represent a profitable process, and provide an acceptable projection for real operating. Additionally, the capacity of the process is another critical factor. The extruding-expelling process and hexane extraction are the two typical approaches used in industry. When the capacities of annual oil production are larger than 12 and 173 million kg respectively, these two processes are profitable. The solvent free approach, known as enzyme assisted aqueous extraction process (EAEP), is profitable when the capacity is larger than 17 million kg of annual oil production. Full article

Diabetes is a condition where the body is incapable of proper utilization of glucose and one that, if not properly managed, can lead to critical illness. Glucose monitoring and decision support is vital in avoiding potential adverse health effects. Current methods mainly involve invasive blood extraction for the purposes of blood glucose level notification, yet such methods rely on active user participation and subjective interpretation of the result. This paper reviews existing research in methods of extraction and monitoring of glucose levels. The purpose of this paper is to examine blood glucose extraction methods in addition to indicators of blood glucose level, toward development of an innovative, non-invasive extraction technology. Decision support methods are also analyzed toward customized, automated, and intelligent diabetic management. Full article

The scope of the current research was to assess the feasibility of encapsulating three commercial antifouling compounds, Irgarol 1051, Econea and Zinc pyrithione, in biodegradable poly(lactic acid) (PLA) nanoparticles. The emulsification–solvent evaporation technique was herein utilized to manufacture nanoparticles with a biocide:polymer ratio of 40%. The loaded nanoparticles were analyzed for their size and size distribution, zeta potential, encapsulation efficiency and thermal properties, while the relevant physicochemical characteristics were correlated to biocide–polymer system. In addition, the encapsulation process was scaled up and the prepared nanoparticles were dispersed in a water-based antifouling paint in order to examine the viability of incorporating nanoparticles in such coatings. Metallic specimens were coated with the nanoparticles-containing paint and examined regarding surface morphology. Full article

This paper proposes a facile strategy for the zwitterionization of bioceramics that is based on the direct incorporation of l-lysine amino acid via the ε-amino group onto mesoporous MCM-41 materials. Fourier transform infrared (FTIR) studies of lysine-grafted MCM-41 (MCM-LYS) simultaneously showed bands at 3080 and 1540 cm⁻¹ and bands at 1625 and 1415 cm⁻¹ corresponding to -NH³⁺/COO⁻ pairs, which demonstrate the incorporation of the amino acid on the material surface keeping its zwitterionic character. Both elemental and thermogravimetric analyses showed that the amount of grafted lysine was 8 wt. % based on the bioceramic total weight. Moreover, MCM-LYS exhibited a reduction of adhesion of S. aureus and E. coli bacteria in 33% and 50%, respectively at physiological pH, as compared with pristine MCM-41. Biofilm studies onto surfaces showed that lysine functionalization elicited a reduction of the area covered by S. aureus biofilm from 42% to only 5% (88%). This research shows a simple and effective approach to chemically modify bioceramics using single amino acids that provides zwitterionic functionality, which is useful to develop new biomaterials that are able to resist bacterial adhesion. Full article

The interindividual variability is an increasingly global problem when treating patients from different backgrounds with diverse customs, metabolism, and necessities. Dose adjustment is frequently based on empirical methods, and therefore, the chance of undesirable side effects to occur is high. Three-dimensional (3D) Printed medicines are revolutionsing the pharmaceutical market as potential tools to achieve personalised treatments adapted to the specific requirements of each patient, taking into account their age, weight, comorbidities, pharmacogenetic, and pharmacokinetic characteristics. Additive manufacturing or 3D printing consists of a wide range of techniques classified in many categories but only three of them are mostly used in the 3D printing of medicines: printing-based inkjet systems, nozzle-based deposition systems, and laser-based writing systems. There are several drawbacks when using each technique and also the type of polymers readily available do not always possess the optimal properties for every drug. The aim of this review is to give an overview about the current techniques employed in 3D printing medicines, highlighting their advantages, disadvantages, along with the polymer and drug requirements for a successful printing. The major application of these techniques will be also discussed. Full article