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Bioengineering, Volume 8, Issue 4 (April 2021) – 7 articles

Cover Story (view full-size image): Lipocalin 2 (Lcn2) overexpression can lead to cancer progression by enhancing tumor angiogenesis. In this study, we engineered a PEGylated liposomal system encapsulating Lcn2 small interfering RNA (Lcn2 siRNA). The PEGylated liposomes were decorated with octreotide (OCT) peptide for targeting breast cancer cells. Optimized OCT-targeted Lcn2 siRNA liposomes (OCT-Lcn2-Lipo) had a mean size of 152 nm and 69.5% encapsulation efficiency. OCT-Lcn2-lipo could achieve 55−60% silencing of Lcn2 mRNA in MCF-7 and MDA-MB-231 cells. In addition, OCT-Lcn2-Lipo demonstrated in vitro anti-angiogenic effects by reducing VEGF-A levels in treated cells. OCT-Lcn2-lipo also reduced the endothelial cell (HUVEC) migration levels. This approach may be useful in inhibiting angiogenesis and metastasis in breast cancer. View this paper
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29 pages, 2446 KiB  
Review
COVID-19 Diagnostic Strategies. Part I: Nucleic Acid-Based Technologies
by Tina Shaffaf and Ebrahim Ghafar-Zadeh
Bioengineering 2021, 8(4), 49; https://doi.org/10.3390/bioengineering8040049 - 17 Apr 2021
Cited by 24 | Viewed by 9030
Abstract
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused respiratory infection, resulting in more than two million deaths globally and hospitalizing thousands of people by March 2021. A considerable percentage of the SARS-CoV-2 positive patients are asymptomatic or pre-symptomatic carriers, facilitating [...] Read more.
The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused respiratory infection, resulting in more than two million deaths globally and hospitalizing thousands of people by March 2021. A considerable percentage of the SARS-CoV-2 positive patients are asymptomatic or pre-symptomatic carriers, facilitating the viral spread in the community by their social activities. Hence, it is critical to have access to commercialized diagnostic tests to detect the infection in the earliest stages, monitor the disease, and follow up the patients. Various technologies have been proposed to develop more promising assays and move toward the mass production of fast, reliable, cost-effective, and portable PoC diagnostic tests for COVID-19 detection. Not only COVID-19 but also many other pathogens will be able to spread and attach to human bodies in the future. These technologies enable the fast identification of high-risk individuals during future hazards to support the public in such outbreaks. This paper provides a comprehensive review of current technologies, the progress in the development of molecular diagnostic tests, and the potential strategies to facilitate innovative developments in unprecedented pandemics. Full article
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26 pages, 872 KiB  
Review
Protein-Based 3D Biofabrication of Biomaterials
by Mahta Mirzaei, Oseweuba Valentine Okoro, Lei Nie, Denise Freitas Siqueira Petri and Amin Shavandi
Bioengineering 2021, 8(4), 48; https://doi.org/10.3390/bioengineering8040048 - 16 Apr 2021
Cited by 35 | Viewed by 6665
Abstract
Protein/peptide-based hydrogel biomaterial inks with the ability to incorporate various cells and mimic the extracellular matrix’s function are promising candidates for 3D printing and biomaterials engineering. This is because proteins contain multiple functional groups as reactive sites for enzymatic, chemical modification or physical [...] Read more.
Protein/peptide-based hydrogel biomaterial inks with the ability to incorporate various cells and mimic the extracellular matrix’s function are promising candidates for 3D printing and biomaterials engineering. This is because proteins contain multiple functional groups as reactive sites for enzymatic, chemical modification or physical gelation or cross-linking, which is essential for the filament formation and printing processes in general. The primary mechanism in the protein gelation process is the unfolding of its native structure and its aggregation into a gel network. This network is then stabilized through both noncovalent and covalent cross-link. Diverse proteins and polypeptides can be obtained from humans, animals, or plants or can be synthetically engineered. In this review, we describe the major proteins that have been used for 3D printing, highlight their physicochemical properties in relation to 3D printing and their various tissue engineering application are discussed. Full article
(This article belongs to the Special Issue 3D Printing of Functional Biomaterials and Nanocomposites)
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14 pages, 4110 KiB  
Article
Lower Limb Kinematics in Individuals with Hip Osteoarthritis during Gait: A Focus on Adaptative Strategies and Interlimb Symmetry
by Micaela Porta, Massimiliano Pau, Bruno Leban, Michela Deidda, Marco Sorrentino, Federico Arippa and Giuseppe Marongiu
Bioengineering 2021, 8(4), 47; https://doi.org/10.3390/bioengineering8040047 - 13 Apr 2021
Cited by 10 | Viewed by 4379
Abstract
Among the functional limitations associated with hip osteoarthritis (OA), the alteration of gait capabilities represents one of the most invalidating as it may seriously compromise the quality of life of the affected individual. The use of quantitative techniques for human movement analysis has [...] Read more.
Among the functional limitations associated with hip osteoarthritis (OA), the alteration of gait capabilities represents one of the most invalidating as it may seriously compromise the quality of life of the affected individual. The use of quantitative techniques for human movement analysis has been found valuable in providing accurate and objective measures of kinematics and kinetics of gait in individuals with hip OA, but few studies have reported in-depth analyses of lower limb joint kinematics during gait and, in particular, there is a scarcity of data on interlimb symmetry. Such aspects were investigated in the present study which tested 11 individuals with hip OA (mean age 68.3 years) and 11 healthy controls age- and sex-matched, using 3D computerized gait analysis to perform point-by-point comparisons of the joint angle trends of hip, knee, and ankle. Angle-angle diagrams (cyclograms) were also built to compute several parameters (i.e., cyclogram area and orientation and Trend Symmetry) from which to assess the degree of interlimb symmetry. The results show that individuals with hip OA exhibit peculiar gait patterns characterized by severe modifications of the physiologic trend at hip level even in the unaffected limb (especially during the stance phase), as well as minor (although significant) alterations at knee and ankle level. The symmetry analysis also revealed that the effect of the disease in terms of interlimb coordination is present at knee joint as well as hip, while the ankle joint appears relatively preserved from specific negative effects from this point of view. The availability of data on such kinematic adaptations may be useful in supporting the design of specific rehabilitative strategies during both preoperative and postoperative periods. Full article
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15 pages, 3693 KiB  
Review
Rejuvenated Stem/Progenitor Cells for Cartilage Repair Using the Pluripotent Stem Cell Technology
by Naoki Nakayama, Sudheer Ravuri and Johnny Huard
Bioengineering 2021, 8(4), 46; https://doi.org/10.3390/bioengineering8040046 - 10 Apr 2021
Cited by 3 | Viewed by 5019
Abstract
It is widely accepted that chondral defects in articular cartilage of adult joints are never repaired spontaneously, which is considered to be one of the major causes of age-related degenerative joint disorders, such as osteoarthritis. Since mobilization of subchondral bone (marrow) cells and [...] Read more.
It is widely accepted that chondral defects in articular cartilage of adult joints are never repaired spontaneously, which is considered to be one of the major causes of age-related degenerative joint disorders, such as osteoarthritis. Since mobilization of subchondral bone (marrow) cells and addition of chondrocytes or mesenchymal stromal cells into full-thickness defects show some degrees of repair, the lack of self-repair activity in adult articular cartilage can be attributed to lack of reparative cells in adult joints. In contrast, during a fetal or embryonic stage, joint articular cartilage has a scar-less repair activity, suggesting that embryonic joints may contain cells responsible for such activity, which can be chondrocytes, chondroprogenitors, or other cell types such as skeletal stem cells. In this respect, the tendency of pluripotent stem cells (PSCs) to give rise to cells of embryonic characteristics will provide opportunity, especially for humans, to obtain cells carrying similar cartilage self-repair activity. Making use of PSC-derived cells for cartilage repair is still in a basic or preclinical research phase. This review will provide brief overviews on how human PSCs have been used for cartilage repair studies. Full article
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15 pages, 2729 KiB  
Article
Biomechanically Tunable Nano-Silica/P-HEMA Structural Hydrogels for Bone Scaffolding
by Raffaella Aversa, Relly Victoria Petrescu, Florian Ion T. Petrescu, Valeria Perrotta, Davide Apicella and Antonio Apicella
Bioengineering 2021, 8(4), 45; https://doi.org/10.3390/bioengineering8040045 - 4 Apr 2021
Cited by 11 | Viewed by 3305
Abstract
Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37 °C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and [...] Read more.
Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37 °C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized by both dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. The mechanical and morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37 °C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of the use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed. Full article
(This article belongs to the Special Issue Hydrogels Used for Biomanufacturing)
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25 pages, 4836 KiB  
Article
Octreotide-Targeted Lcn2 siRNA PEGylated Liposomes as a Treatment for Metastatic Breast Cancer
by Vrinda Gote and Dhananjay Pal
Bioengineering 2021, 8(4), 44; https://doi.org/10.3390/bioengineering8040044 - 3 Apr 2021
Cited by 12 | Viewed by 5450
Abstract
Lcn2 overexpression in metastatic breast cancer (MBC) can lead to cancer progression by inducing the epithelial-to-mesenchymal transition and enhancing tumor angiogenesis. In this study, we engineered a PEGylated liposomal system encapsulating lipocalin 2 (Lcn2) small interfering RNA (Lcn2 siRNA) for selective targeting MBC [...] Read more.
Lcn2 overexpression in metastatic breast cancer (MBC) can lead to cancer progression by inducing the epithelial-to-mesenchymal transition and enhancing tumor angiogenesis. In this study, we engineered a PEGylated liposomal system encapsulating lipocalin 2 (Lcn2) small interfering RNA (Lcn2 siRNA) for selective targeting MBC cell line MCF-7 and triple-negative breast cancer cell line MDA-MB-231. The PEGylated liposomes were decorated with octreotide (OCT) peptide. OCT is an octapeptide analog of somatostatin growth hormone, having affinity for somatostatin receptors, overexpressed on breast cancer cells. Optimized OCT-targeted Lcn2 siRNA encapsulated PEGylated liposomes (OCT-Lcn2-Lipo) had a mean size of 152.00 nm, PDI, 0.13, zeta potential 4.10 mV and entrapment and loading efficiencies of 69.5% and 7.8%, respectively. In vitro uptake and intracellular distribution of OCT-Lcn2-Lipo in MCF-7 and MDA-MB-231 and MCF-12A cells demonstrated higher uptake for the OCT-targeted liposomes at 6 h by flow cytometry and confocal microscopy. OCT-Lcn2-lipo could achieve approximately 55−60% silencing of Lcn2 mRNA in MCF-7 and MDA-MB-231 cells. OCT-Lcn2-Lipo also demonstrated in vitro anti-angiogenic effects in MCF-7 and MDA-MB-231 cells by reducing VEGF-A and reducing the endothelial cells (HUVEC) migration levels. This approach may be useful in inhibiting angiogenesis in MBC. Full article
(This article belongs to the Special Issue Novel Expansions and Trends in Gene Diagnostics and Gene Therapy)
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13 pages, 2417 KiB  
Article
Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery
by Jihoon Kim, Jee Seon Kim, Kyung Hyun Min, Young-Hwa Kim and Xiaoyuan Chen
Bioengineering 2021, 8(4), 43; https://doi.org/10.3390/bioengineering8040043 - 29 Mar 2021
Cited by 5 | Viewed by 3875
Abstract
Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs [...] Read more.
Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody–drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs. Full article
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