Bioengineering

12 pages, 1027 KiB

Open AccessArticle

Supervised Analysis for Phenotype Identification: The Case of Heart Failure Ejection Fraction Class

by Cristina Lopez, Jose Luis Holgado, Raquel Cortes, Inma Sauri, Antonio Fernandez, Jose Miguel Calderon, Julio Nuñez and Josep Redon

Bioengineering 2021, 8(6), 85; https://doi.org/10.3390/bioengineering8060085 - 21 Jun 2021

Cited by 2 | Viewed by 3076

Abstract

Artificial Intelligence is creating a paradigm shift in health care, with phenotyping patients through clustering techniques being one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), [...] Read more.

Artificial Intelligence is creating a paradigm shift in health care, with phenotyping patients through clustering techniques being one of the areas of interest. Objective: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data from Electronic Health Records (EHR). Subjects and methods: 2854 subjects over 25 years old with a diagnosis of HF and LVEF, measured by echocardiography, were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. The performance of the developed algorithm was tested in heart failure patients from Primary Care. To select the most influentual variables, the LASSO algorithm setting was used, and to tackle the issue of one class exceeding the other one by a large amount, we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. Results: The full XGBoost model obtained the maximum accuracy, a high negative predictive value, and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence EF value. Applied in the EHR dataset, with a total of 25,594 patients with an ICD-code of HF and no regular follow-up in cardiology clinics, 6170 (21.1%) were identified as pertaining to the reduced EF group. Conclusion: The obtained algorithm was able to identify a number of HF patients with reduced ejection fraction, who could benefit from a protocol with a strong possibility of success. Furthermore, the methodology can be used for studies using data extracted from the Electronic Health Records. Full article

(This article belongs to the Special Issue Machine Learning-Based Heart, Brain and Nerve Tissue Engineering)

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19 pages, 9508 KiB

Open AccessArticle

Analysis and Forecasting Incidence, Intensive Care Unit Admissions, and Projected Mortality Attributable to COVID-19 in Portugal, the UK, Germany, Italy, and France: Predictions for 4 Weeks Ahead

by Kathleen Carvalho, João Paulo Vicente, Mihajlo Jakovljevic and João Paulo Ramos Teixeira

Bioengineering 2021, 8(6), 84; https://doi.org/10.3390/bioengineering8060084 - 11 Jun 2021

Cited by 11 | Viewed by 3972

Abstract

The use of artificial neural networks (ANNs) is a great contribution to medical studies since the application of forecasting concepts allows for the analysis of future diseases propagation. In this context, this paper presents a study of the new coronavirus SARS-COV-2 with a [...] Read more.

The use of artificial neural networks (ANNs) is a great contribution to medical studies since the application of forecasting concepts allows for the analysis of future diseases propagation. In this context, this paper presents a study of the new coronavirus SARS-COV-2 with a focus on verifying the virus propagation associated with mitigation procedures and massive vaccination campaigns. There were two proposed methodologies in making predictions 28 days ahead for the number of new cases, deaths, and ICU patients of five European countries: Portugal, France, Italy, the United Kingdom, and Germany. A case study of the results of massive immunization in Israel was also considered. The data input of cases, deaths, and daily ICU patients was normalized to reduce discrepant numbers due to the countries’ size and the cumulative vaccination values by the percentage of population immunized (with at least one dose of the vaccine). As a comparative criterion, the calculation of the mean absolute error (MAE) of all predictions presents the best methodology, targeting other possibilities of use for the method proposed. The best architecture achieved a general MAE for the 1-to-28-day ahead forecast, which is lower than 30 cases, 0.6 deaths, and 2.5 ICU patients per million people. Full article

(This article belongs to the Special Issue Bioengineering Techniques and Applications Against COVID-19)

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11 pages, 3726 KiB

Open AccessArticle

adipoSIGHT in Therapeutic Response: Consequences in Osteosarcoma Treatment

by Banani Kundu, Virginia Brancato, Joaquim Oliveira, Vitor M. Correlo, Rui L. Reis and Subhas C. Kundu

Bioengineering 2021, 8(6), 83; https://doi.org/10.3390/bioengineering8060083 - 10 Jun 2021

Cited by 3 | Viewed by 3772

Abstract

Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement of stem cells is [...] Read more.

Chemotherapeutic resistance is a major problem in effective cancer treatment. Cancer cells engage various cells or mechanisms to resist anti-cancer therapeutics, which results in metastasis and the recurrence of disease. Considering the cellular heterogeneity of cancer stroma, the involvement of stem cells is reported to affect the proliferation and metastasis of osteosarcoma. Hence, the duo (osteosarcoma: Saos 2 and human adipose-derived stem cells: ASCs) is co-cultured in present study to investigate the therapeutic response using a nonadherent, concave surface. Staining with a cell tracker allows real-time microscopic monitoring of the cell arrangement within the sphere. Cell–cell interaction is investigated by means of E-cadherin expression. Comparatively high expression of E-cadherin and compact organization is observed in heterotypic tumorspheres (Saos 2–ASCs) compared to homotypic ones (ASCs), limiting the infiltration of chemotherapeutic compound doxorubicin into the heterotypic tumorsphere, which in turn protects cells from the toxic effect of the chemotherapeutic. In addition, genes known to be associated with drug resistance, such as SOX2, OCT4, and CD44 are overexpressed in heterotypic tumorspheres post-chemotherapy, indicating that the duo collectively repels the effect of doxorubicin. The interaction between ASCs and Saos 2 in the present study points toward the growing oncological risk of using ASC-based regenerative therapy in cancer patients and warrants further investigation. Full article

(This article belongs to the Special Issue Biomaterials Approaches for Disease Modeling)

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14 pages, 2233 KiB

Open AccessArticle

Strategy for Managing Industrial Anaerobic Sludge through the Heterotrophic Cultivation of Chlorella sorokiniana: Effect of Iron Addition on Biomass and Lipid Production

by Esteban Charria-Girón, Vanessa Amazo, Daniela De Angulo, Eliana Hidalgo, María Francisca Villegas-Torres, Frank Baganz and Nelson. H. Caicedo Ortega

Bioengineering 2021, 8(6), 82; https://doi.org/10.3390/bioengineering8060082 - 10 Jun 2021

Cited by 5 | Viewed by 3981

Abstract

Microalgae provides an alternative for the valorization of industrial by-products, in which the nutritional content varies substantially and directly affects microalgae system performance. Herein, the heterotrophic cultivation of Chlorella sorokiniana was systematically studied, allowing us to detect a nutritional deficiency other than the [...] Read more.

Microalgae provides an alternative for the valorization of industrial by-products, in which the nutritional content varies substantially and directly affects microalgae system performance. Herein, the heterotrophic cultivation of Chlorella sorokiniana was systematically studied, allowing us to detect a nutritional deficiency other than the carbon source through assessing the oxygen transfer rate for glucose or acetate fermentation. Consequently, a mathematical model of the iron co-limiting effect on heterotrophic microalgae was developed by exploring its ability to regulate the specific growth rate and yield. For instance, higher values of the specific growth rate (0.17 h⁻¹) compared with those reported for the heterotrophic culture of Chlorella were obtained due to iron supplementation. Therefore, anaerobic sludge from an industrial wastewater treatment plant (a baker’s yeast company) was pretreated to obtain an extract as a media supplement for C. sorokiniana. According to the proposed model, the sludge extract allowed us to supplement iron values close to the growth activation concentration (K_Fe ~12 mg L⁻¹). Therefore, a fed-batch strategy was evaluated on nitrogen-deprived cultures supplemented with the sludge extract to promote biomass formation and fatty acid synthesis. Our findings reveal that nitrogen and iron in sludge extract can supplement heterotrophic cultures of Chlorella and provide an alternative for the valorization of industrial anaerobic sludge. Full article

(This article belongs to the Special Issue Bioengineering in Remediation of Polluted Environments)

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Graphical abstract

13 pages, 19414 KiB

Open AccessCommunication

Versatile Vessel-on-a-Chip Platform for Studying Key Features of Blood Vascular Tumors

by Marina Llenas, Roberto Paoli, Natalia Feiner-Gracia, Lorenzo Albertazzi, Josep Samitier and David Caballero

Bioengineering 2021, 8(6), 81; https://doi.org/10.3390/bioengineering8060081 - 9 Jun 2021

Cited by 13 | Viewed by 4936

Abstract

Tumor vessel-on-a-chip systems have attracted the interest of the cancer research community due to their ability to accurately recapitulate the multiple dynamic events of the metastatic cascade. Vessel-on-a-chip microfluidic platforms have been less utilized for investigating the distinctive features and functional heterogeneities of [...] Read more.

Tumor vessel-on-a-chip systems have attracted the interest of the cancer research community due to their ability to accurately recapitulate the multiple dynamic events of the metastatic cascade. Vessel-on-a-chip microfluidic platforms have been less utilized for investigating the distinctive features and functional heterogeneities of tumor-derived vascular networks. In particular, vascular tumors are characterized by the massive formation of thrombi and severe bleeding, a rare and life-threatening situation for which there are yet no clear therapeutic guidelines. This is mainly due to the lack of technological platforms capable of reproducing these characteristic traits of the pathology in a simple and well-controlled manner. Herein, we report the fabrication of a versatile tumor vessel-on-a-chip platform to reproduce, investigate, and characterize the massive formation of thrombi and hemorrhage on-chip in a fast and easy manner. Despite its simplicity, this method offers multiple advantages to recapitulate the pathophysiological events of vascular tumors, and therefore, may find useful applications in the field of vascular-related diseases, while at the same time being an alternative to more complex approaches. Full article

(This article belongs to the Special Issue Three-Dimensional Models of Pediatric Cancers)

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31 pages, 1517 KiB

Open AccessSystematic Review

Carbon Nanotube-Based Scaffolds for Cardiac Tissue Engineering—Systematic Review and Narrative Synthesis

by Louie Scott, Izabela Jurewicz, Kamalan Jeevaratnam and Rebecca Lewis

Bioengineering 2021, 8(6), 80; https://doi.org/10.3390/bioengineering8060080 - 9 Jun 2021

Cited by 14 | Viewed by 4862

Abstract

Cardiovascular disease is currently the top global cause of death, however, research into new therapies is in decline. Tissue engineering is a solution to this crisis and in combination with the use of carbon nanotubes (CNTs), which have drawn recent attention as a [...] Read more.

Cardiovascular disease is currently the top global cause of death, however, research into new therapies is in decline. Tissue engineering is a solution to this crisis and in combination with the use of carbon nanotubes (CNTs), which have drawn recent attention as a biomaterial, could facilitate the development of more dynamic and complex in vitro models. CNTs’ electrical conductivity and dimensional similarity to cardiac extracellular proteins provide a unique opportunity to deliver scaffolds with stimuli that mimic the native cardiac microenvironment in vitro more effectively. This systematic review aims to evaluate the use and efficacy of CNTs for cardiac tissue scaffolds and was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Three databases were searched: PubMed, Scopus, and Web of Science. Papers resulting from these searches were then subjected to analysis against pre-determined inclusion and quality appraisal criteria. From 249 results, 27 manuscripts met the criteria and were included in this review. Neonatal rat cardiomyocytes were most commonly used in the experiments, with multi-walled CNTs being most common in tissue scaffolds. Immunofluorescence was the experimental technique most frequently used, which was employed for the staining of cardiac-specific proteins relating to contractile and electrophysiological function. Full article

(This article belongs to the Collection Nanoparticles for Therapeutic and Diagnostic Applications)

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18 pages, 3075 KiB

Open AccessEditor’s ChoiceArticle

3D Printing of Thermoresponsive Hydrogel Laden with an Antimicrobial Agent towards Wound Healing Applications

by Martyna Nizioł, Justyna Paleczny, Adam Junka, Amin Shavandi, Anna Dawiec-Liśniewska and Daria Podstawczyk

Bioengineering 2021, 8(6), 79; https://doi.org/10.3390/bioengineering8060079 - 8 Jun 2021

Cited by 47 | Viewed by 8703

Abstract

Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept^®, [...] Read more.

Thermoresponsive hydrogel-based wound dressings with an incorporated antimicrobial agent can be fabricated employing 3D printing technology. A novel printable ink containing poly(N-isopropylacrylamide) (PNIPAAm) precursors, sodium alginate (ALG), methylcellulose (MC) that is laden with a mixture of octenidine dihydrochloride and 2-phenoxyethanol (Octenisept^®, OCT) possess accurate printability and shape fidelity. This study also provides the protocol of ink’s use for the 3D printing of hydrogel scaffolds. The hydrogel’s physicochemical properties and drug release profiles from the hydrogel specimens to the external solution have been determined at two temperatures (20 and 37 °C). The release test showed a sustained OCT delivery into ultrapure water and the PBS solution. The temperature-responsive hydrogel exhibited antimicrobial activity against Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa and demonstrated non-cytotoxicity towards fibroblasts. The thermoresponsive behavior along with biocompatibility, antimicrobial activity, and controlled drug release make this hydrogel a promising class of materials for wound dressing applications. Full article

(This article belongs to the Special Issue 3D Printing of Functional Biomaterials and Nanocomposites)

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13 pages, 1483 KiB

Open AccessArticle

At-Line Reversed Phase Liquid Chromatography for In-Process Monitoring of Inclusion Body Solubilization

by Julian Ebner, Diana Humer, Robert Klausser, Viktor Rubus, Reinhard Pell, Oliver Spadiut and Julian Kopp

Bioengineering 2021, 8(6), 78; https://doi.org/10.3390/bioengineering8060078 - 7 Jun 2021

Cited by 3 | Viewed by 4282

Abstract

Refolding is known as the bottleneck in inclusion body (IB) downstream processing in the pharmaceutical industry: high dilutions leading to large operating volumes, slow refolding kinetics and low refolding yields are only a few of the problems that impede industrial application. Solubilization prior [...] Read more.

Refolding is known as the bottleneck in inclusion body (IB) downstream processing in the pharmaceutical industry: high dilutions leading to large operating volumes, slow refolding kinetics and low refolding yields are only a few of the problems that impede industrial application. Solubilization prior to refolding is often carried out empirically and the effects of the solubilizate on the subsequent refolding step are rarely investigated. The results obtained in this study, however, indicate that the quality of the IB solubilizate has a severe effect on subsequent refolding. As the solubilizate contains chaotropic reagents in high molarities, it is commonly analyzed with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). SDS-PAGE, however, suffers from a long analysis time, making at-line analytical implementation difficult. In this study, we established an at-line reversed phase liquid chromatography method to investigate the time-dependent quality of the solubilizate. To verify the necessity of at-line solubilization monitoring, we varied the essential solubilization conditions for horseradish peroxidase IBs. The solubilization time was found to have a major influence on subsequent refolding, underlining the high need for an at-line analysis of solubilization. Furthermore, we used the developed reversed phase liquid chromatography method for an in-process control (IPC). In conclusion, the presented reversed phase liquid chromatography method allows a proper control of IB solubilization applicable for tailored refolding. Full article

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16 pages, 2612 KiB

Open AccessArticle

Different Microfluidic Environments for In Vitro Testing of Lipid Nanoparticles against Osteosarcoma

by Oihane Mitxelena-Iribarren, Sara Lizarbe-Sancha, Jay Campisi, Sergio Arana and Maite Mujika

Bioengineering 2021, 8(6), 77; https://doi.org/10.3390/bioengineering8060077 - 4 Jun 2021

Cited by 6 | Viewed by 3750

Abstract

The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment than traditional treatment methods. Although the combination of target therapy with nanotechnology created new hope for cancer treatment, methodological issues during [...] Read more.

The use of lipid nanoparticles as biodegradable shells for controlled drug delivery shows promise as a more effective and targeted tumor treatment than traditional treatment methods. Although the combination of target therapy with nanotechnology created new hope for cancer treatment, methodological issues during in vitro validation of nanovehicles slowed their application. In the current work, the effect of methotrexate (MTX) encapsulated in different matrices was evaluated in a dynamic microfluidic platform. Effects on the viability of osteosarcoma cells in the presence of recirculation of cell media, free MTX and two types of blank and drug-containing nanoparticles were successfully assessed in different tumor-mimicking microenvironments. Encapsulated MTX was more effective than the equal dose free drug treatment, as cell death significantly increased under the recirculation of both types of drug-loaded nanoparticles in all concentrations. In fact, MTX-nanoparticles reduced cell population 50 times more than the free drug when 150-µM drug dose was recirculated. Moreover, when compared to the equivalent free drug dose recirculation, cell number was reduced 60 and 100 points more under recirculation of each nanoparticle with a 15-µM drug concentration. Thus, the results obtained with the microfluidic model present MTX-lipid nanoparticles as a promising and more effective therapy for pediatric osteosarcoma treatment than current treatment options. Full article

(This article belongs to the Special Issue Three-Dimensional Models of Pediatric Cancers)

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18 pages, 6337 KiB

Open AccessReview

Regenerative Strategies in Cleft Palate: An Umbrella Review

by Inês Francisco, Anabela Baptista Paula, Bárbara Oliveiros, Maria Helena Fernandes, Eunice Carrilho, Carlos Miguel Marto and Francisco Vale

Bioengineering 2021, 8(6), 76; https://doi.org/10.3390/bioengineering8060076 - 3 Jun 2021

Cited by 6 | Viewed by 5956

Abstract

(1) Background: Alveolar bone defects or decreased alveolar bone height and width may have different causes, such as cleft palate. Regenerative procedures in oro-dental defects are challenging due to anatomical factors and the distinct cell populations involved. The iliac crest bone graft remains [...] Read more.

(1) Background: Alveolar bone defects or decreased alveolar bone height and width may have different causes, such as cleft palate. Regenerative procedures in oro-dental defects are challenging due to anatomical factors and the distinct cell populations involved. The iliac crest bone graft remains the gold-standard for cleft palate closure. However, tissue regeneration approaches have been employed and their outcome reviewed, but no conclusions have been made about which one is the gold-standard. (2) Methods: this umbrella review aims to critically appraise the effectiveness of the current approaches in bone defects regeneration in non-syndromic patients with cleft palate. A search was performed in PubMed, Cochrane Library, Scopus, Web of Science and EMBASE databases. (3) Results: Systematic reviews of randomized and non-randomized controlled trials with or without meta-analysis were included. Nine articles were included in the qualitative analysis and five in the quantitative one. The included studies quality was evaluated with AMSTAR2. (4) Conclusions: The use of new regenerative strategies, such as bone morphogenic protein 2, appears to provide similar results regarding bone volume, filling, and height to the standard technique with the iliac crest bone graft. Full article

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15 pages, 2994 KiB

Open AccessArticle

Fibrin Glue Implants Seeded with Dental Pulp and Periodontal Ligament Stem Cells for the Repair of Periodontal Bone Defects: A Preclinical Study

by Natella I. Enukashvily, Julia A. Dombrovskaya, Anastasia V. Kotova, Natalia Semenova, Irina Karabak, Roman E. Banashkov, Dmitry Baram, Tatiana Paderina, Stanislav S. Bilyk, Wolf-Dieter Grimm, Anton N. Kovalenko, Dmitry Ivolgin, Egor M. Prikhodko and Alexey V. Silin

Bioengineering 2021, 8(6), 75; https://doi.org/10.3390/bioengineering8060075 - 1 Jun 2021

Cited by 9 | Viewed by 4470

Abstract

A technology to create a cell-seeded fibrin-based implant matching the size and shape of bone defect is required to create an anatomical implant. The aim of the study was to develop a technology of cell-seeded fibrin gel implant creation that has the same [...] Read more.

A technology to create a cell-seeded fibrin-based implant matching the size and shape of bone defect is required to create an anatomical implant. The aim of the study was to develop a technology of cell-seeded fibrin gel implant creation that has the same shape and size as the bone defect at the site of implantation. Using computed tomography (CT) images, molds representing bone defects were created by 3D printing. The form was filled with fibrin glue and human dental pulp stem cells (DPSC). The viability, set of surface markers and osteogenic differentiation of DPSC grown in fibrin gel along with the clot retraction time were evaluated. In mice, an alveolar bone defect was created. The defect was filled with fibrin gel seeded with mouse DPSC. After 28 days, the bone repair was analyzed with cone beam CT and by histological examination. The proliferation rate, set of surface antigens and osteogenic potential of cells grown inside the scaffold and in 2D conditions did not differ. In mice, both cell-free and mouse DPSC-seeded implants increased the bone tissue volume and vascularization. In mice with cell-seeded gel implants, the bone remodeling process was more prominent than in animals with a cell-free implant. The technology of 3D-printed forms for molding implants can be used to prepare implants using components that are not suitable for 3D printing. Full article

(This article belongs to the Special Issue Cell Sheet Engineering for Stem Cell Delivery and Tissue Modeling)

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16 pages, 6087 KiB

Open AccessArticle

Modeling Focused-Ultrasound Response for Non-Invasive Treatment Using Machine Learning

by Tariq Mohammad Arif, Zhiming Ji, Md Adilur Rahim and Bharath Babu Nunna

Bioengineering 2021, 8(6), 74; https://doi.org/10.3390/bioengineering8060074 - 1 Jun 2021

Cited by 3 | Viewed by 4119

Abstract

The interactions between body tissues and a focused ultrasound beam can be evaluated using various numerical models. Among these, the Rayleigh–Sommerfeld and angular spectrum methods are considered to be the most effective in terms of accuracy. However, they are computationally expensive, which is [...] Read more.

The interactions between body tissues and a focused ultrasound beam can be evaluated using various numerical models. Among these, the Rayleigh–Sommerfeld and angular spectrum methods are considered to be the most effective in terms of accuracy. However, they are computationally expensive, which is one of the underlying issues of most computational models. Typically, evaluations using these models require a significant amount of time (hours to days) if realistic scenarios such as tissue inhomogeneity or non-linearity are considered. This study aims to address this issue by developing a rapid estimation model for ultrasound therapy using a machine learning algorithm. Several machine learning models were trained on a very-large dataset (19,227 simulations), and the performance of these models were evaluated with metrics such as Root Mean Squared Error (RMSE), R-squared (R²), Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC). The resulted random forest provides superior accuracy with an R² value of 0.997, an RMSE of 0.0123, an AIC of −82.56, and a BIC of −81.65 on an external test dataset. The results indicate the efficacy of the random forest-based model for the focused ultrasound response, and practical adoption of this approach will improve the therapeutic planning process by minimizing simulation time. Full article

(This article belongs to the Special Issue Smart Nano Biomedical Devices in Advanced Healthcare)

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26 pages, 755 KiB

Open AccessArticle

Thermo-Viscoelastic Response of Protein-Based Hydrogels

by Aleksey D. Drozdov and Jesper deClaville Christiansen

Bioengineering 2021, 8(6), 73; https://doi.org/10.3390/bioengineering8060073 - 31 May 2021

Cited by 3 | Viewed by 3519

Abstract

Because of the bioactivity and biocompatibility of protein-based gels and the reversible nature of bonds between associating coiled coils, these materials demonstrate a wide spectrum of potential applications in targeted drug delivery, tissue engineering, and regenerative medicine. The kinetics of rearrangement (association and [...] Read more.

Because of the bioactivity and biocompatibility of protein-based gels and the reversible nature of bonds between associating coiled coils, these materials demonstrate a wide spectrum of potential applications in targeted drug delivery, tissue engineering, and regenerative medicine. The kinetics of rearrangement (association and dissociation) of the physical bonds between chains has been traditionally studied in shear relaxation tests and small-amplitude oscillatory tests. A characteristic feature of recombinant protein gels is that chains in the polymer network are connected by temporary bonds between the coiled coil complexes and permanent cross-links between functional groups of amino acids. A simple model is developed for the linear viscoelastic behavior of protein-based gels. Its advantage is that, on the one hand, the model only involves five material parameters with transparent physical meaning and, on the other, it correctly reproduces experimental data in shear relaxation and oscillatory tests. The model is applied to study the effects of temperature, the concentration of proteins, and their structure on the viscoelastic response of hydrogels. Full article

(This article belongs to the Special Issue Engineered Biomaterials: Design, Modeling, Synthesis, Characterization and Applications)

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Graphical abstract

11 pages, 459 KiB

Open AccessArticle

Blood Glucose Level Forecasting on Type-1-Diabetes Subjects during Physical Activity: A Comparative Analysis of Different Learning Techniques

by Benedetta De Paoli, Federico D’Antoni, Mario Merone, Silvia Pieralice, Vincenzo Piemonte and Paolo Pozzilli

Bioengineering 2021, 8(6), 72; https://doi.org/10.3390/bioengineering8060072 - 26 May 2021

Cited by 11 | Viewed by 3693

Abstract

Background: Type 1 Diabetes Mellitus (T1DM) is a widespread chronic disease in industrialized countries. Preventing blood glucose levels from exceeding the euglycaemic range would reduce the incidence of diabetes-related complications and improve the quality of life of subjects with T1DM. As a consequence, [...] Read more.

Background: Type 1 Diabetes Mellitus (T1DM) is a widespread chronic disease in industrialized countries. Preventing blood glucose levels from exceeding the euglycaemic range would reduce the incidence of diabetes-related complications and improve the quality of life of subjects with T1DM. As a consequence, in the last decade, many Machine Learning algorithms aiming to forecast future blood glucose levels have been proposed. Despite the excellent performance they obtained, the prediction of abrupt changes in blood glucose values produced during physical activity (PA) is still one of the main challenges. Methods: A Jump Neural Network was developed in order to overcome the issue of predicting blood glucose values during PA. Three learning configurations were developed and tested: offline training, online training, and online training with reinforcement. All configurations were tested on six subjects suffering from T1DM that held regular PA (three aerobic and three anaerobic) and exploited Continuous Glucose Monitoring (CGM). Results: The forecasting performance was evaluated in terms of the Root-Mean-Squared-Error (RMSE), according to a paradigm of Precision Medicine. Conclusions: The online learning configurations performed better than the offline configuration in total days but not on the only CGM associated with the PA; thus, the results do not justify the increased computational burden because the improvement was not significant. Full article

(This article belongs to the Special Issue The New Frontiers of Artificial Organs Engineering)

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14 pages, 5217 KiB

Open AccessArticle

In-House, Fast FDM Prototyping of a Custom Cutting Guide for a Lower-Risk Pediatric Femoral Osteotomy

by Leonardo Frizziero, Gian Maria Santi, Christian Leon-Cardenas, Giampiero Donnici, Alfredo Liverani, Paola Papaleo, Francesca Napolitano, Curzio Pagliari, Giovanni Luigi Di Gennaro, Stefano Stallone, Stefano Stilli, Giovanni Trisolino and Paola Zarantonello

Bioengineering 2021, 8(6), 71; https://doi.org/10.3390/bioengineering8060071 - 26 May 2021

Cited by 17 | Viewed by 4442

Abstract

Three-dimensional printed custom cutting guides (CCGs) are becoming more and more investigated in medical literature, as a patient-specific approach is often desired and very much needed in today’s surgical practice. Three-dimensional printing applications and computer-aided surgical simulations (CASS) allow for meticulous preoperatory planning [...] Read more.

Three-dimensional printed custom cutting guides (CCGs) are becoming more and more investigated in medical literature, as a patient-specific approach is often desired and very much needed in today’s surgical practice. Three-dimensional printing applications and computer-aided surgical simulations (CASS) allow for meticulous preoperatory planning and substantial reductions of operating time and risk of human error. However, several limitations seem to slow the large-scale adoption of 3D printed CCGs. CAD designing and 3D printing skills are inevitably needed to develop workflow and address the study; therefore, hospitals are pushed to include third-party collaboration, from highly specialized medical centers to industrial engineering companies, thus increasing the time and cost of labor. The aim of this study was to move towards the feasibility of an in-house, low-cost CCG 3D printing methodology for pediatric orthopedic (PO) surgery. The prototype of a femoral cutting guide was developed for its application at the IOR—Rizzoli Orthopedic Institute of Bologna. The element was printed with an entry-level 3D printer with a high-temperature PLA fiber, whose thermomechanical properties can withstand common steam heat sterilization without bending or losing the original geometry. This methodology allowed for extensive preoperatory planning that would likewise reduce the overall surgery time, whilst reducing the risks related to the intervention. Full article

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