Bioengineering — Open Access Journal

Impedance pumping is a mechanism that generates flow in a compliant vessel by repeatedly actuating the vessel asymmetrically, without employing any internal valves, blades, or other mechanisms. The net flow is obtained by establishing a constructive wave pattern. Elaborate studies of impedance pumping in a single vessel have shown that the flow rate strongly depends on the actuation frequency, as well as on other parameters, such as actuator location and amplitude, and that it operates best in the resonance mode. The present study extends these principles to a network of multiple compliant vessels, representing a cardiovascular system. The flow is modeled numerically by the one-dimensional approximation of the Navier-Stokes equations. Two configurations were examined, systems consisting of three and five compliant vessels. First, the natural frequencies of these configurations were identified. Then, the dependence of the net flow rate (NFR) on the actuating frequency was explored, showing that impedance pumping operates best in the resonance mode in the case of a network of vessels as well. The impact of other parameters were studied as well, such as the location of one or two actuators, actuation amplitude, actuator width, the duty cycle, and the phase lag between the actuators. The results show that impedance pumps can generate significant NFR and the obtained NFR can be manipulated by properly setting up one or more of the governing parameters. These findings indicate that impedance pumping principles may be applied to flow control of the cardiovascular system. Full article

Purpose: Evaluation of the performance of a computer-aided diagnosis (CAD) system based on the quantified color distribution in strain elastography imaging to evaluate the malignancy of breast tumors. Methods: The database consisted of 31 malignant and 52 benign lesions. A radiologist who was blinded to the diagnosis performed the visual analysis of the lesions. After six months with no eye contact on the breast images, the same radiologist and other two radiologists manually drew the contour of the lesions in B-mode ultrasound, which was masked in the elastography image. In order to measure the amount of hard tissue in a lesion, we developed a CAD system able to identify the amount of hard tissue, represented by red color, and quantify its predominance in a lesion, allowing classification as soft, intermediate, or hard. The data obtained with the CAD system were compared with the visual analysis. We calculated the sensitivity, specificity, and area under the curve (AUC) for the classification using the CAD system from the manual delineation of the contour by each radiologist. Results: The performance of the CAD system for the most experienced radiologist achieved sensitivity of 70.97%, specificity of 88.46%, and AUC of 0.853. The system presented better performance compared with his visual diagnosis, whose sensitivity, specificity, and AUC were 61.29%, 88.46%, and 0.829, respectively. The system obtained sensitivity, specificity, and AUC of 67.70%, 84.60%, and 0.783, respectively, for images segmented by Radiologist 2, and 51.60%, 92.30%, and 0.771, respectively, for those segmented by the Resident. The intra-class correlation coefficient was 0.748. The inter-observer agreement of the CAD system with the different contours was good in all comparisons. Conclusions: The proposed CAD system can improve the radiologist performance for classifying breast masses, with excellent inter-observer agreement. It could be a promising tool for clinical use. Full article

In situ vascular tissue engineering aims to regenerate vessels “at the target site” using synthetic scaffolds that are capable of inducing endogenous regeneration. Critical to the success of this approach is a fine balance between functional neo-tissue formation and scaffold degradation. Circulating immune cells are important regulators of this process as they drive the host response to the scaffold and they play a central role in scaffold resorption. Despite the progress made with synthetic scaffolds, little is known about the host response and neo-tissue development during and after scaffold resorption. In this study, we designed a fast-degrading biodegradable supramolecular scaffold for arterial applications and evaluated this development in vivo. Bisurea-modified polycaprolactone (PCL2000-U4U) was electrospun in tubular scaffolds and shielded by non-degradable expanded polytetrafluoroethylene in order to restrict transmural and transanastomotic cell ingrowth. In addition, this shield prevented graft failure, permitting the study of neo-tissue and host response development after degradation. Scaffolds were implanted in 60 healthy male Lewis rats as an interposition graft into the abdominal aorta and explanted at different time points up to 56 days after implantation to monitor sequential cell infiltration, differentiation, and tissue formation in the scaffold. Endogenous tissue formation started with an acute immune response, followed by a dominant presence of pro-inflammatory macrophages during the first 28 days. Next, a shift towards tissue-producing cells was observed, with a striking increase in α-Smooth Muscle Actin-positive cells and extracellular matrix by day 56. At that time, the scaffold was resorbed and immune markers were low. These results suggest that neo-tissue formation was still in progress, while the host response became quiescent, favoring a regenerative tissue outcome. Future studies should confirm long-term tissue homeostasis, but require the strengthening of the supramolecular scaffold if a non-shielded model will be used. Full article

A proof of concept for a one-pot process merging a heterocycle formation by a classical chemical approach at basic conditions with a biocatalytic reduction, running at neutral pH conditions, is reported. A crucial component for this process is the compartmentalization of the single reactions by the use of polydimethylsiloxane thimbles. This process was applied successfully towards an asymmetric synthesis of (S)-2,2,3-trimethyl-1-thia-4-azaspiro[4.4]nonane, leading to excellent enantioselectivities of 99% enantiomeric excess (ee). Full article

Cell-hydrogel based therapies offer great promise for wound healing. The specific aim of this study was to assess the viability of human hepatocellular carcinoma (HepG2) cells immobilized in atomized alginate capsules (3.5% (w/v) alginate, d = 225 µm ± 24.5 µm) post-extrusion through a three-dimensional (3D) printed methacrylate-based custom hollow microneedle assembly (circular array of 13 conical frusta) fabricated using stereolithography. With a jetting reliability of 80%, the solvent-sterilized device with a root mean square roughness of 158 nm at the extrusion nozzle tip (d = 325 μm) was operated at a flowrate of 12 mL/min. There was no significant difference between the viability of the sheared and control samples for extrusion times of 2 h (p = 0.14, α = 0.05) and 24 h (p = 0.5, α = 0.05) post-atomization. Factoring the increase in extrusion yield from 21.2% to 56.4% attributed to hydrogel bioerosion quantifiable by a loss in resilience from 5470 (J/m³) to 3250 (J/m³), there was no significant difference in percentage relative payload (p = 0.2628, α = 0.05) when extrusion occurred 24 h (12.2 ± 4.9%) when compared to 2 h (9.9 ± 2.8%) post-atomization. Results from this paper highlight the feasibility of encapsulated cell extrusion, specifically protection from shear, through a hollow microneedle assembly reported for the first time in literature. Full article

Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple localizations might be challenging. For this reason, many computational approaches have been developed in the last decades to quantify the skeletal tumor burden and treatment response. In this review, we analyzed the progressive development and diffusion of such approaches. A computerized literature search of the PubMed/Medline was conducted, including articles between January 2008 and March 2018. The search was expanded by manually reviewing the reference list of the chosen articles. Thirty-five studies were identified. The number of eligible studies greatly increased over time. Studies could be categorized in the following categories: automated analysis of 2D scans, SUV-based thresholding, hybrid CT- and SUV-based thresholding, and MRI-based thresholding. All methods are discussed in detail. Automated analysis of bone tumor burden in mCRPC is a growing field of research; when choosing the appropriate method of analysis, it is important to consider the possible advantages as well as the limitations thoroughly. Full article

Cell culture and cell scaffold engineering have previously developed in two directions. First can be ‘static into dynamic’, with proven effects that dynamic cultures have benefits over static ones. Researches in this direction have used several mechanical means, like external vibrators or shakers, to approximate the dynamic environments in real tissue, though such approaches could only partly address the issue. Second, can be ‘2D into 3D’, that is, artificially created three-dimensional (3D) passive (also called ‘static’) scaffolds have been utilized for 3D cell culture, helping external culturing conditions mimic real tissue 3D environments in a better way as compared with traditional two-dimensional (2D) culturing. In terms of the fabrication of 3D scaffolds, 3D printing (3DP) has witnessed its high popularity in recent years with ascending applicability, and this tendency might continue to grow along with the rapid development in scaffold engineering. In this review, we first introduce cell culturing, then focus 3D cell culture scaffold, vibration stimulation for dynamic culture, and 3DP technologies fabricating 3D scaffold. Potential interconnection of these realms will be analyzed, as well as the limitations of current 3D scaffold and vibration mechanisms. In the recommendation part, further discussion on future scaffold engineering regarding 3D vibratory scaffold will be addressed, indicating 3DP as a positive bridging technology for future scaffold with integrated and localized vibratory functions. Full article

Engineering design of microbioreactors (MBRs) and organ-on-chip (OoC) devices can take advantage of established design science theory, in which systematic evaluation of functional concepts and user requirements are analyzed. This is commonly referred to as a conceptual design. This review article compares how common conceptual design principles are applicable to MBR and OoC devices. The complexity of this design, which is exemplified by MBRs for scaled-down cell cultures in bioprocess development and drug testing in OoCs for heart and eye, is discussed and compared with previous design solutions of MBRs and OoCs, from the perspective of how similarities in understanding design from functionality and user purpose perspectives can more efficiently be exploited. The review can serve as a guideline and help the future design of MBR and OoC devices for cell culture studies. Full article

Gelatin-methacryloyl (GelMA) is a semi-synthetic hydrogel which consists of gelatin derivatized with methacrylamide and methacrylate groups. These hydrogels provide cells with an optimal biological environment (e.g., RGD motifs for adhesion) and can be quickly photo-crosslinked, which provides shape fidelity and stability at physiological temperature. In the present work, we demonstrated how GelMA hydrogels can be synthesized with a specific degree of functionalization (DoF) and adjusted to the intended application as a three-dimensional (3D) cell culture platform. The focus of this work lays on producing hydrogel scaffolds which provide a cell promoting microenvironment for human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and are conductive to their adhesion, spreading, and proliferation. The control of mechanical GelMA properties by variation of concentration, DoF, and ultraviolet (UV) polymerization conditions is described. Moreover, hAD-MSC cell viability and morphology in GelMA of different stiffness was evaluated and compared. Polymerized hydrogels with and without cells could be digested in order to release encapsulated cells without loss of viability. We also demonstrated how hydrogel viscosity can be increased by the use of biocompatible additives, in order to enable the extrusion bioprinting of these materials. Taken together, we demonstrated how GelMA hydrogels can be used as a versatile tool for 3D cell cultivation. Full article

Background: Current resorbable and non-resorbable membranes act as a physical barrier to avoid connective and epithelial tissue downgrowth into the defect, favoring the regeneration of periodontal tissues. These conventional membranes possess many structural and bio-functional limitations. We hypothesized that the next-generation of guided tissue regeneration (GTR) membranes for periodontal tissue engineering will be a biologically active, spatially designed nanofibrous biomaterial that closely mimics the native extra-cellular matrix (ECM). Methods: GTR membranes made of poly(ε-Caprolactone) with a molecular weight of 80,000 reinforced with different weight concentrations of nano-Hydroxyapatite/Bioactive glass (2%, 5%, 10%, 15%) is fabricated by the method of electrospinning. After fabrication, in vitro properties are evaluated. Results: The electrospun nanofibrous membranes possessed excellent mechanical properties initially and after one month of degradation in phosphate buffer solution (PBS). Moreover, none of the fabricated membranes were found to be cytotoxic at lower concentrations and higher concentrations. Comparing the overall properties, PCL (poly(e-caprolactone)) + BG (Bioactive glass) 2% exhibited superior cell attachment and percentage of viable cells, increased fiber and pore diameter which satisfies the ideal properties needed for GTR membranes. Conclusion: Composite nanofibrous membranes prepared by electrospinning are suitable for use as a GTR membrane and are a useful prototype for further development of a final membrane for clinical use. Full article

Gel dosimeters are attractive detectors for radiation therapy, with properties similar to biological tissue and the potential to visualize volumetric dose distributions. Radio-fluorogenesis is the yield of fluorescent chemical products in response to energy deposition from ionizing radiation. This report shares the development of a novel radio-fluorogenic gel (RFG) dosimeter, gelatin infused with coumarin-3-carboxlyic acid (C3CA), for the quantification of imparted energy. Aqueous solutions exposed to ionizing radiation result in the production of hydroxyl free radicals through water radiolysis. Interactions between hydroxyl free radicals and coumarin-3-carboxylic acid produce a fluorescent product. 7-hydroxy-coumarin-3-carboxylic acid has a blue (445 nm) emission following ultra-violet (UV) to near UV (365–405 nm) excitation. Effects of C3CA concentration and pH buffers were investigated. The response of the RFG was explored with respect to strength, type, and exposure rate of high-energy radiation. Results show a linear dose response relationship independent of energy and type, with a dose-rate dependency. This report demonstrates increased photo-yield with high pH and the utility of gelatin-RFG for phantom studies of radiation dosimetry. Full article

Adipose tissue is involved in many physiological processes. Therefore, the need for adipose tissue-like analogues either for soft tissue reconstruction or as in vitro testing platforms is undeniable. In this work, we explored the natural features of gellan gum (GG) to recreate injectable stable adipose-like microtissues. GG hydrogel particles with different percentages of polymer (0.5%, 0.75%, 1.25%) were developed and the effect of obtained mechanical properties over the ability of hASCs to differentiate towards the adipogenic lineage was evaluated based on the expression of the early (PPARγ) and late (FABP4) adipogenic markers, and on lipids formation and accumulation. Constructs were cultured in adipogenic induction medium up to 21 days or for six days in induction plus nine days in maintenance media. Overall, no significant differences were observed in terms of hASCs adipogenic differentiation within the range of Young’s moduli between 2.7 and 12.9 kPa. The long-term (up to six weeks) stability of the developed constructs supported its application in soft tissue reconstruction. Moreover, their ability to function as adipose-like microtissue models for drug screening was demonstrated by confirming its sensitivity to TNFα and ROCK inhibitor, respectively involved in the repression and induction of the adipogenic differentiation. Full article

Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment. Full article

Lignocellulosic feedstocks present a growing interest in many industrial processes as they are an ecological alternative to petroleum-based products. Generally, the size of plant raw materials needs to be reduced by milling step(s), to increase density, facilitate transport and storage, and to increase reactivity. However, this unit operation can prove to be important in term of investments, functioning costs, and energy consumption if the process is not fully adapted to the histological structure of the plant material, possibly challenging the profitability of the whole chain of the biomass conversion. In this paper, the different technologies that can be used for the milling of lignocellulosic biomass were reviewed and different avenues are suggested to improve the milling performances thanks to thermal pretreatments. Based on examples on wheat straw milling, the main points to take into consideration in the choice of a milling technologies have been highlighted in regards to the specifications of ground powder. A specific focus on the hazards associated to the milling and the manipulation of fine biomass particles is also realized at the end of the paper from the perspective of industrial applications. Full article

A low percentage of novel drug candidates succeed and reach the end of the drug discovery pipeline, mainly due to poor initial screening and assessment of the effects of the drug and its metabolites over various tissues in the human body. For that, emerging technologies involving the production of organoids from human pluripotent stem cells (hPSCs) and the use of organ-on-a-chip devices are showing great promise for developing a more reliable, rapid and cost-effective drug discovery process when compared with the current use of animal models. In particular, the possibility of virtually obtaining any type of cell within the human body, in combination with the ability to create patient-specific tissues using human induced pluripotent stem cells (hiPSCs), broadens the horizons in the fields of drug discovery and personalized medicine. In this review, we address the current progress and challenges related to the process of obtaining organoids from different cell lineages emerging from hPSCs, as well as how to create devices that will allow a precise examination of the in vitro effects generated by potential drugs in different organ systems. Full article

Mesenchymal stem cells (MSCs) are considered as primary candidates for cell-based therapies due to their multiple effects in regenerative medicine. Pre-conditioning of MSCs under physiological conditions—such as hypoxia, three-dimensional environments, and dynamic cultivation—prior to transplantation proved to optimize their therapeutic efficiency. When cultivated as three-dimensional aggregates or spheroids, MSCs display increased angiogenic, anti-inflammatory, and immunomodulatory effects as well as improved stemness and survival rates after transplantation, and cultivation under dynamic conditions can increase their viability, proliferation, and paracrine effects, alike. Only few studies reported to date, however, have utilized dynamic conditions for three-dimensional aggregate cultivation of MSCs. Still, the integration of dynamic bioreactor systems, such as spinner flasks or stirred tank reactors might pave the way for a robust, scalable bulk expansion of MSC aggregates or MSC-derived extracellular vesicles. This review summarizes recent insights into the therapeutic potential of MSC aggregate cultivation and focuses on dynamic generation and cultivation techniques of MSC aggregates. Full article

Oral health represents an essential component in the quality of life of people, being a determinant factor in general health since it may affect the risk of suffering other conditions, such as chronic diseases. Oral diseases have become one of the main public health problems, where dental caries is the condition that most affects oral health worldwide, occurring in about 90% of the global population. This condition has been considered a challenge because of its high prevalence, besides being a chronic but preventable disease which can be caused depending on the consumption of certain nutritional elements interacting simultaneously with different factors, such as socioeconomic factors. Based on this problem, an analysis of a set of 189 dietary and demographic determinants is performed in this work, in order to find the relationship between these factors and the oral situation of a set of subjects. The oral situation refers to the presence and absence/restorations of caries. The methodology is performed constructing a dense artificial neural network (ANN), as a computer-aided diagnosis tool, looking for a generalized model that allows for classifying subjects. As validation, the classification model was evaluated through a statistical analysis based on a cross validation, calculating the accuracy, loss function, receiving operating characteristic (ROC) curve and area under the curve (AUC) parameters. The results obtained were statistically significant, obtaining an accuracy ≃ 0.69 and AUC values of 0.69 and 0.75. Based on these results, it is possible to conclude that the classification model developed through the deep ANN is able to classify subjects with absence of caries from subjects with presence or restorations with high accuracy, according to their demographic and dietary factors. Full article