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Bioengineering, Volume 9, Issue 2 (February 2022) – 43 articles

Cover Story (view full-size image): The established structure-property relationship and biochemical composition of major ampullate spider silk provides it with an impressive balance of strength and elasticity, unrivaled by synthetic materials. Other biologically inspired small peptide motifs correlated to specific functionalities can be combined with this unit to create designer silk material with new hybrid properties. Four concatenated repeats of the heparin-binding motif, ARKKAAKA, were genetically linked with MaSp2 amino acid motifs (GPGXXAn) to produce a mechanically robust protein capable of both binding biologically active heparin and resisting pathogen colonization, potentially enabling both in vivo anticoagulation and anti-infectivity. The anticoagulant activity of this fusion protein was comparable to the activity of surface-bound heparin. View this paper
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Review
Measuring Biosignals with Single Circuit Boards
Bioengineering 2022, 9(2), 84; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020084 - 21 Feb 2022
Cited by 1 | Viewed by 841
Abstract
To measure biosignals constantly, using textile-integrated or even textile-based electrodes and miniaturized electronics, is ideal to provide maximum comfort for patients or athletes during monitoring. While in former times, this was usually solved by integrating specialized electronics into garments, either connected to a [...] Read more.
To measure biosignals constantly, using textile-integrated or even textile-based electrodes and miniaturized electronics, is ideal to provide maximum comfort for patients or athletes during monitoring. While in former times, this was usually solved by integrating specialized electronics into garments, either connected to a handheld computer or including a wireless data transfer option, nowadays increasingly smaller single circuit boards are available, e.g., single-board computers such as Raspberry Pi or microcontrollers such as Arduino, in various shapes and dimensions. This review gives an overview of studies found in the recent scientific literature, reporting measurements of biosignals such as ECG, EMG, sweat and other health-related parameters by single circuit boards, showing new possibilities offered by Arduino, Raspberry Pi etc. in the mobile long-term acquisition of biosignals. The review concentrates on the electronics, not on textile electrodes about which several review papers are available. Full article
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Article
Systematic Investigation of the Effects of Multiple SV40 Nuclear Localization Signal Fusion on the Genome Editing Activity of Purified SpCas9
Bioengineering 2022, 9(2), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020083 - 21 Feb 2022
Viewed by 684
Abstract
The emergence of CRISPR-Cas9 technology has revolutionized both basic and translational biomedical research. For Cas9 nuclease to exert genome editing activity, nuclear localization signal (NLS) derived from simian virus 40 (SV40) T antigen is commonly installed as genetic fusion to direct the intracellular [...] Read more.
The emergence of CRISPR-Cas9 technology has revolutionized both basic and translational biomedical research. For Cas9 nuclease to exert genome editing activity, nuclear localization signal (NLS) derived from simian virus 40 (SV40) T antigen is commonly installed as genetic fusion to direct the intracellular Cas9 proteins to the nucleus of cells. Notably, previous studies have shown that multiple SV40 NLS fusion can improve the targeting activity of Cas9-derived genome-editing and base-editing tools. In addition, the multi-NLS fusion can increase the intracellular activity of Cas9 in the forms of both constitutive expression and directly delivered Cas9-guide RNA ribonucleoprotein (RNP) complex. However, the relationship between NLS fusion and intracellular Cas9 activity has not been fully understood, including the dependency of activity on the number or organization of NLS fusion. In the present study, we constructed and purified a set of Streptococcus pyogenes Cas9 (SpCas9) variants containing one to four NLS repeats at the N- or C-terminus of the proteins and systematically analyzed the effects of multi-NLS fusion on the activity of SpCas9 RNPs. It was found that multi-NLS fusion could improve the intracellular activity as lipofected or nucleofected Cas9 RNPs. Importantly, multi-NLS fusion could enhance the genome-editing activity of SpCas9 RNPs in primary and stem/progenitor cells and mouse embryos. Full article
(This article belongs to the Special Issue Novel Expansions and Trends in Gene Diagnostics and Gene Therapy)
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Review
Development of Novel Tetrapyrrole Structure Photosensitizers for Cancer Photodynamic Therapy
Bioengineering 2022, 9(2), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020082 - 19 Feb 2022
Cited by 1 | Viewed by 839
Abstract
The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and [...] Read more.
The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions. Nevertheless, the clinical use of the first-generation PS (sodium porfimer and hematoporphyrins) revealed difficulties, such as long-term skin photosensitivity, insufficient penetration into deep-seated tumors and incorrect localization to it. The second generation is based on different approaches of the synthesis and conjugation of porphyrin PS with biomolecules, which made it possible to approach the targeted PDT of tumors. Despite the fact that the development of the second-generation PS started about 30 years ago, these technologies are still in demand and are in intensive development, especially in the direction of improving the process of optimization split linkers responsive to input. Bioconjugation and encapsulation by targeting molecules are among the main strategies for developing of the PS synthesis. A targeted drug delivery system with the effect of increased permeability and retention by tumor cells is one of the ultimate goals of the synthesis of second-generation PS. This review presents porphyrin PS of various generations, discusses factors affecting cellular biodistribution and uptake, and indicates their role as diagnostic and therapeutic (theranostic) agents. New complexes based on porphyrin PS for photoimmunotherapy are presented, where specific antibodies are used that are chemically bound to PS, absorbing light from the near infrared part of the spectrum. Additionally, a two-photon photodynamic approach using third-generation photosensitizers for the treatment of tumors is discussed, which indicates the prospects for the further development of a promising method antitumor PDT. Full article
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Article
Automated Cell Foreground–Background Segmentation with Phase-Contrast Microscopy Images: An Alternative to Machine Learning Segmentation Methods with Small-Scale Data
Bioengineering 2022, 9(2), 81; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020081 - 18 Feb 2022
Viewed by 748
Abstract
Cell segmentation is a critical step for image-based experimental analysis. Existing cell segmentation methods are neither entirely automated nor perform well under basic laboratory microscopy. This study proposes an efficient and automated cell segmentation method involving morphological operations to automatically achieve cell segmentation [...] Read more.
Cell segmentation is a critical step for image-based experimental analysis. Existing cell segmentation methods are neither entirely automated nor perform well under basic laboratory microscopy. This study proposes an efficient and automated cell segmentation method involving morphological operations to automatically achieve cell segmentation for phase-contrast microscopes. Manual/visual counting of cell segmentation serves as the control group (156 images as ground truth) to evaluate the proposed method’s performance. The proposed technology’s adaptive performance is assessed at varying conditions, including artificial blurriness, illumination, and image size. Compared to the Trainable Weka Segmentation method, the Empirical Gradient Threshold method, and the ilastik segmentation software, the proposed method achieved better segmentation accuracy (dice coefficient: 90.07, IoU: 82.16%, and 6.51% as the average relative error on measuring cell area). The proposed method also has good reliability, even under unfavored imaging conditions at which manual labeling or human intervention is inefficient. Additionally, similar degrees of segmentation accuracy were confirmed when the ground truth data and the generated data from the proposed method were applied individually to train modified U-Net models (16848 images). These results demonstrated good accuracy and high practicality of the proposed cell segmentation method with phase-contrast microscopy image data. Full article
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Article
A Multiscale Partition-Based Kolmogorov–Sinai Entropy for the Complexity Assessment of Heartbeat Dynamics
Bioengineering 2022, 9(2), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020080 - 16 Feb 2022
Viewed by 699
Abstract
Background: Several methods have been proposed to estimate complexity in physiological time series observed at different time scales, with a particular focus on heart rate variability (HRV) series. In this frame, while several complexity quantifiers defined in the multiscale domain have already been [...] Read more.
Background: Several methods have been proposed to estimate complexity in physiological time series observed at different time scales, with a particular focus on heart rate variability (HRV) series. In this frame, while several complexity quantifiers defined in the multiscale domain have already been investigated, the effectiveness of a multiscale Kolmogorov–Sinai (K-S) entropy has not been evaluated yet for the characterization of heartbeat dynamics. Methods: The use of the algorithmic information content, which is estimated through an effective compression algorithm, is investigated to quantify multiscale partition-based K-S entropy on publicly available experimental HRV series gathered from young and elderly subjects undergoing a visual elicitation task (Fantasia). Moreover, publicly available HRV series gathered from healthy subjects, as well as patients with atrial fibrillation and congestive heart failure in unstructured conditions have been analyzed as well. Results: Elderly people are associated with a lower HRV complexity and a more predictable cardiovascular dynamics, with significantly lower partition-based K-S entropy than the young adults. Major differences between these groups occur at partitions greater than six. In case of partition cardinality greater than 5, patients with congestive heart failure show a minimal predictability, while atrial fibrillation shows a higher variability, and hence complexity, which is actually reduced by the time coarse-graining procedure. Conclusions: The proposed multiscale partition-based K-S entropy is a viable tool to investigate complex cardiovascular dynamics in different physiopathological states. Full article
(This article belongs to the Special Issue Advances in Multivariate Physiological Signal Analysis)
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Article
Bioleaching of Heavy Metals from Printed Circuit Boards with an Acidophilic Iron-Oxidizing Microbial Consortium in Stirred Tank Reactors
Bioengineering 2022, 9(2), 79; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020079 - 16 Feb 2022
Viewed by 1122
Abstract
In this study, bioleaching was carried out for the recovery of metals (copper, zinc, tin, lead, gold and silver) from printed circuit boards residues (PCBs), one of the most important wastes from electrical and electronic equipment, using an acidophilic iron-oxidizing bacterial consortium enriched [...] Read more.
In this study, bioleaching was carried out for the recovery of metals (copper, zinc, tin, lead, gold and silver) from printed circuit boards residues (PCBs), one of the most important wastes from electrical and electronic equipment, using an acidophilic iron-oxidizing bacterial consortium enriched with minerals from a gold mine in the Arequipa region, Peru. High-throughput sequencing and analysis of the 16S rRNA biomarker revealed that this consortium was predominantly composed of Tissierella, Acidiphilium and Leptospirillum bacteria, from which the latter is known to grow by chemolithotrophy through iron oxidation. After the enrichment process, the acidophilic iron-oxidizing consortium was first tested for its tolerance to different PCBs concentrations, showing best growth up to 10 g/L of PCBs and a tolerance index of 0.383. Based on these results, the bioleaching efficiency of the consortium was investigated for 10 g/L of PCBs in stirred tank reactors coupled to an aeration system, for 18 days. High bioleaching efficiencies were achieved for copper and zinc (69% and 91%, respectively), indicating that these two metals can be easily extracted in this leaching system. Lower extraction efficiencies were achieved for tin (16%) and gold (28%), while for lead and silver only a residual recovery (<0.25%) was detected. These results indicate that the enriched bacterial consortium originating from the Arequipa region, Peru, has a high capacity to recover different metals of economic importance. Full article
(This article belongs to the Section Biochemical Engineering)
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Article
Environmental Factors Modulate the Role of orf21 Sigma Factor in Clavulanic Acid Production in Streptomyces Clavuligerus ATCC27064
Bioengineering 2022, 9(2), 78; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020078 - 16 Feb 2022
Viewed by 701
Abstract
Sigma factors and sigma factor-related mechanisms control antibiotic production in Streptomyces. In this contribution, the orf21 gene was overexpressed in the wild-type strain of Streptomyces clavuligerus ATCC2764, yielding S. clavuligerus/pIORF21, to further evaluate its regulatory effect on clavulanic acid (CA) biosynthesis [...] Read more.
Sigma factors and sigma factor-related mechanisms control antibiotic production in Streptomyces. In this contribution, the orf21 gene was overexpressed in the wild-type strain of Streptomyces clavuligerus ATCC2764, yielding S. clavuligerus/pIORF21, to further evaluate its regulatory effect on clavulanic acid (CA) biosynthesis under different culture medium conditions. The orf21 overexpression, regulated under the constitutive promoter ermE*, led to 2.6-fold increase in CA production in GSPG medium, and a 1.8-fold decrease using ISP medium. As for GYM and MYM media, S. clavuligerus/pIORF21 strain showed higher aerial mycelium production compared to control. Glycerol uptake rate profile was affected by orf21 overexpression. Furthermore, in GSPG, S. clavuligerus/pIORF21 slightly increased the expression of adpA and gcas genes, whilst, in ISP, the claR gene expression was drastically reduced, which is consistent with a decreased CA production, observed in this medium. These findings suggest the protein encoded by the orf21 gene plays a role in the regulation of CA biosynthesis as a response to the nutritional composition of the medium. Full article
(This article belongs to the Special Issue Strategies for the Efficient Development of Microbial Bioprocesses)
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Article
A Second-Generation Nanoluc-IL27 Fusion Cytokine for Targeted-Gene-Therapy Applications
Bioengineering 2022, 9(2), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020077 - 16 Feb 2022
Viewed by 591
Abstract
An emerging approach in treating skeletal malignancies utilizes osteoimmunology to investigate new multifunctional immune-stimulatory agents that can simultaneously combat tumor growth and promote bone repair. We have hypothesized that cytokine Interleukin-27 (IL-27) is an excellent candidate biologic to help rebalance the prostate tumor [...] Read more.
An emerging approach in treating skeletal malignancies utilizes osteoimmunology to investigate new multifunctional immune-stimulatory agents that can simultaneously combat tumor growth and promote bone repair. We have hypothesized that cytokine Interleukin-27 (IL-27) is an excellent candidate biologic to help rebalance the prostate tumor cells and bone cell environment. In this work, we examined the proof of principle for a short, secreted luciferase (Nanoluc or Nluc) fusion with IL-27 to produce a novel cytokine-based biologic (Nluc-27), whereby we examined its efficacy in vitro in reducing prostate tumor growth and rebalancing bone cell proliferation and differentiation. This work demonstrates the targeting and anti-tumor efficacy of the Nluc-27 fusion cytokine in cancer and bone cell models. The fusion cytokine is detectable in conditioned media, and bioactive in different cell systems. This novel Nluc-27 cytokine will allow flexible incorporation of other targeting domains and may serve as flexible tool to augment IL-27′s bioactivity and reengineer its efficacy against prostate tumor or bone cells, and may prove applicable to several other cell types for targeted gene therapy applications. Full article
(This article belongs to the Special Issue Novel Expansions and Trends in Gene Diagnostics and Gene Therapy)
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Article
Biomechanical Evaluation of Recurrent Dissociation of Modular Humeral Prostheses
Bioengineering 2022, 9(2), 76; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020076 - 16 Feb 2022
Viewed by 528
Abstract
The purpose of the study was to evaluate the force and torque required to dissociate a humeral head from the unimplanted modular total shoulder replacement system from different manufacturers and to determine if load and torque to dissociation are reduced in the presence [...] Read more.
The purpose of the study was to evaluate the force and torque required to dissociate a humeral head from the unimplanted modular total shoulder replacement system from different manufacturers and to determine if load and torque to dissociation are reduced in the presence of bodily fluids. Impingement, taper contamination, lack of compressive forces, and interference of taper fixation by the proximal humerus have all been reported as possible causes for dissociation. Experimental values determined in this research were compared with literature estimates of dissociation force of the humeral head under various conditions to gain more understanding of the causes of recurrent dissociations of the humeral head. This study examined biomechanical properties under dry and wet conditions under clinically practiced methods. Mean load to dissociation (1513 N ± 508 N) was found to be greater than that exerted by the activities of daily living (578 N) for all implants studied. The mean torque to dissociation was (49.77 N·m ± 19.07 N·m). Analysis of R2 correlation coefficients and p-values (α = 0.05) did not show any significant correlation between dry/bovine, dry/wet, or wet/bovine for load, displacement, or torsional stiffness in the majority of tests performed. Wetting the taper with water or bovine serum did not reduce the dissociation force to a statistically significant degree. Torque and lack of compressive forces at the rotator cuff may be the cause of dissociation at values less than those of activities of daily living. Torque data are provided by this study, but further research is needed to fully appreciate the role of torque in recurrent dissociations. Full article
(This article belongs to the Section Regenerative Engineering)
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Review
The History and Innovations of Blood Vessel Anastomosis
Bioengineering 2022, 9(2), 75; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020075 - 15 Feb 2022
Viewed by 710
Abstract
Surgical technique and technology frequently coevolve. The brief history of blood vessel anastomosis is full of famous names. While the techniques pioneered by these surgeons have been well described, the technology that facilitated their advancements and their inventors deserve recognition. The mass production [...] Read more.
Surgical technique and technology frequently coevolve. The brief history of blood vessel anastomosis is full of famous names. While the techniques pioneered by these surgeons have been well described, the technology that facilitated their advancements and their inventors deserve recognition. The mass production of laboratory microscopes in the mid-1800s allowed for an explosion of interest in tissue histology. This improved understanding of vascular physiology and thrombosis laid the groundwork for Carrel and Guthrie to report some of the first successful vascular anastomoses. In 1916, McLean discovered heparin. Twenty-four years later, Gordon Murray found that it could prevent thrombosis when performing end-to-end anastomosis. These discoveries paved the way for the first-in-human kidney transplantations. Otolaryngologists Nylen and Holmgren were the first to bring the laboratory microscope into the operating room, but Jacobson was the first to apply these techniques to microvascular anastomosis. His first successful attempt in 1960 and the subsequent development of microsurgical tools allowed for an explosion of interest in microsurgery, and several decades of innovation followed. Today, new advancements promise to make microvascular and vascular surgery faster, cheaper, and safer for patients. The future of surgery will always be inextricably tied to the creativity and vision of its innovators. Full article
(This article belongs to the Special Issue Bioengineered Strategies for Surgical Innovation)
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Review
A New Wave of Industrialization of PHA Biopolyesters
Bioengineering 2022, 9(2), 74; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020074 - 15 Feb 2022
Cited by 5 | Viewed by 1311
Abstract
The ever-increasing use of plastics, their fossil origin, and especially their persistence in nature have started a wave of new innovations in materials that are renewable, offer the functionalities of plastics, and are biodegradable. One such class of biopolymers, polyhydroxyalkanoates (PHAs), are biosynthesized [...] Read more.
The ever-increasing use of plastics, their fossil origin, and especially their persistence in nature have started a wave of new innovations in materials that are renewable, offer the functionalities of plastics, and are biodegradable. One such class of biopolymers, polyhydroxyalkanoates (PHAs), are biosynthesized by numerous microorganisms through the conversion of carbon-rich renewable resources. PHA homo- and heteropolyesters are intracellular products of secondary microbial metabolism. When isolated from microbial biomass, PHA biopolymers mimic the functionalities of many of the top-selling plastics of petrochemical origin, but biodegrade in soil, freshwater, and marine environments, and are both industrial- and home-compostable. Only a handful of PHA biopolymers have been studied in-depth, and five of these reliably match the desired material properties of established fossil plastics. Realizing the positive attributes of PHA biopolymers, several established chemical companies and numerous start-ups, brand owners, and converters have begun to produce and use PHA in a variety of industrial and consumer applications, in what can be described as the emergence of the “PHA industry”. While this positive industrial and commercial relevance of PHA can hardly be described as the first wave in its commercial development, it is nonetheless a very serious one with over 25 companies and start-ups and 30+ brand owners announcing partnerships in PHA production and use. The combined product portfolio of the producing companies is restricted to five types of PHA, namely poly(3-hydroxybutyrate), poly(4-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxybutyrate-co-4-hydroxybutyrate), and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), even though PHAs as a class of polymers offer the potential to generate almost limitless combinations of polymers beneficial to humankind. To date, by varying the co-monomer type and content in these PHA biopolymers, their properties emulate those of the seven top-selling fossil plastics, representing 230 million t of annual plastics production. Capacity expansions of 1.5 million t over the next 5 years have been announced. Policymakers worldwide have taken notice and are encouraging industry to adopt biodegradable and compostable material solutions. This wave of commercialization of PHAs in single-use and in durable applications holds the potential to make the decisive quantum leap in reducing plastic pollution, the depletion of fossil resources, and the emission of greenhouse gases and thus fighting climate change. This review presents setbacks and success stories of the past 40 years and the current commercialization wave of PHA biopolymers, their properties, and their fields of application. Full article
(This article belongs to the Special Issue Advances in Polyhydroxyalkanoate (PHA) Production, Volume 3)
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Article
PMMA-Cement-PLIF Is Safe and Effective as a Single-Stage Posterior Procedure in Treating Pyogenic Erosive Lumbar Spondylodiscitis—A Single-Center Retrospective Study of 73 Cases
Bioengineering 2022, 9(2), 73; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020073 - 15 Feb 2022
Viewed by 606
Abstract
Background: Surgical treatment for erosive pyogenic spondylodiscitis of the lumbar spine is challenging as, following debridement of the intervertebral and bony abscess, a large and irregular defect is created. Sufficient defect reconstruction with conventional implants using a posterior approach is often impossible. Therefore, [...] Read more.
Background: Surgical treatment for erosive pyogenic spondylodiscitis of the lumbar spine is challenging as, following debridement of the intervertebral and bony abscess, a large and irregular defect is created. Sufficient defect reconstruction with conventional implants using a posterior approach is often impossible. Therefore, we developed the “Cement-PLIF”, a single-stage posterior lumbar procedure, combining posterior lumbar interbody fusion (PLIF) with defect-filling using antibiotic-loaded polymethylmethacrylate (PMMA). This study first describes and evaluates the procedure’s efficacy, safety, and infection eradication rate. Radiological implant stability, bone-regeneration, sagittal profile reconstruction, procedure-related complications, and pre-existing comorbidities were further analyzed. Methods: A retrospective cohort study analyzing 73 consecutive patients with a minimum of a one-year follow-up from 2000–2017. Patient-reported pain levels and improvement in infectious serological parameters evaluated the clinical outcome. Sagittal profile reconstruction, anterior bone-regeneration, and posterior fusion were analyzed in a.p. and lateral radiographs. A Kaplan–Meier analysis was used to determine the impact of pre-existing comorbidities on mortality. Pre-existing comorbidities were quantified using the Charlson-Comorbidity Index (CCI). Results: Mean follow-up was 3.3 (range: 1–16; ±3.2) years. There was no evidence of infection persistence in all patients at the one-year follow-up. One patient underwent revision surgery for early local infection recurrence (1.4%). Five (6.9%) patients required an early secondary intervention at the same level due to minor complications. Radiological follow-up revealed implant stability in 70/73 (95.9%) cases. Successful sagittal reconstruction was demonstrated in all patients (p < 0.001). There was a significant correlation between Kaplan–Meier survival and the number of pre-existing comorbidities (24-months-survival: CCI ≤ 3: 100%; CCI ≥ 3: 84.6%; p = 0.005). Conclusions: The Cement-PLIF procedure for pyogenic erosive spondylodiscitis is an effective and safe treatment as evaluated by infection elimination, clinical outcome, restoration, and maintenance of stability and sagittal alignment. Full article
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Review
COVID-19 Vaccines: An Overview of Different Platforms
Bioengineering 2022, 9(2), 72; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020072 - 12 Feb 2022
Cited by 1 | Viewed by 1115
Abstract
Vaccination is one of the key strategies to stop the COVID-19 pandemic. This review aims to evaluate the current state of vaccine development and to determine the issues that merit additional research. We conducted a literature review of the development of COVID-19 vaccines, [...] Read more.
Vaccination is one of the key strategies to stop the COVID-19 pandemic. This review aims to evaluate the current state of vaccine development and to determine the issues that merit additional research. We conducted a literature review of the development of COVID-19 vaccines, their effectiveness, and their use in special patient groups. To date, 140 vaccines are in clinical development. Vector, RNA, subunit, and inactivated vaccines, as well as DNA vaccines, have been approved for human use. Vector vaccines have been well studied prior to the COVID-19 pandemic; however, their long-term efficacy and approaches to scaling up their production remain questionable. The main challenge for RNA vaccines is to improve their stability during production, storage, and transportation. For inactivated vaccines, the key issue is to improve their immunogenicity and effectiveness. To date, it has been shown that the immunogenicity of COVID-19 vaccines directly correlates with their clinical efficacy. In view of the constant mutation, the emerging new SARS-CoV-2 variants have been shown to be able to partially escape post-vaccination immune response; however, most vaccines remain sufficiently effective regardless of the variant of the virus. One of the promising strategies to improve the effectiveness of vaccination, which is being studied, is the use of different platforms within a single vaccination course. Despite significant progress in the development and study of COVID-19 vaccines, there are many issues that require further research. Full article
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Article
Biologically Inspired Optimal Terminal Iterative Learning Control for the Swing Phase of Gait in a Hybrid Neuroprosthesis: A Modeling Study
Bioengineering 2022, 9(2), 71; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020071 - 12 Feb 2022
Viewed by 617
Abstract
(1) Background: An iterative learning control (ILC) strategy was developed for a “Muscle First” Motor-Assisted Hybrid Neuroprosthesis (MAHNP). The MAHNP combines a backdrivable exoskeletal brace with neural stimulation technology to enable persons with paraplegia due to spinal cord injury (SCI) to execute ambulatory [...] Read more.
(1) Background: An iterative learning control (ILC) strategy was developed for a “Muscle First” Motor-Assisted Hybrid Neuroprosthesis (MAHNP). The MAHNP combines a backdrivable exoskeletal brace with neural stimulation technology to enable persons with paraplegia due to spinal cord injury (SCI) to execute ambulatory motions and walk upright. (2) Methods: The ILC strategy was developed to swing the legs in a biologically inspired ballistic fashion. It maximizes muscular recruitment and activates the motorized exoskeletal bracing to assist the motion as needed. The control algorithm was tested using an anatomically realistic three-dimensional musculoskeletal model of the lower leg and pelvis suitably modified to account for exoskeletal inertia. The model was developed and tested with the OpenSim biomechanical modeling suite. (3) Results: Preliminary data demonstrate the efficacy of the controller in swing-leg simulations and its ability to learn to balance muscular and motor contributions to improve performance and accomplish consistent stepping. In particular, the controller took 15 iterations to achieve the desired outcome with 0.3% error. Full article
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Article
Top-Down Detection of Eating Episodes by Analyzing Large Windows of Wrist Motion Using a Convolutional Neural Network
Bioengineering 2022, 9(2), 70; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020070 - 11 Feb 2022
Viewed by 601
Abstract
In this work, we describe a new method to detect periods of eating by tracking wrist motion during everyday life. Eating uses hand-to-mouth gestures for ingestion, each of which lasts a few seconds. Previous works have detected these gestures individually and then aggregated [...] Read more.
In this work, we describe a new method to detect periods of eating by tracking wrist motion during everyday life. Eating uses hand-to-mouth gestures for ingestion, each of which lasts a few seconds. Previous works have detected these gestures individually and then aggregated them to identify meals. The novelty of our approach is that we analyze a much longer window (0.5–15 min) using a convolutional neural network. Longer windows can contain other gestures related to eating, such as cutting or manipulating food, preparing foods for consumption, and resting between ingestion events. The context of these other gestures can improve the detection of periods of eating. We test our methods on the public Clemson all-day dataset, which consists of 354 recordings containing 1063 eating episodes. We found that accuracy at detecting eating increased by 15% in ≥4 min windows compared to ≤15 s windows. Using a 6 min window, we detected 89% of eating episodes, with 1.7 false positives for every true positive (FP/TP). These are the best results achieved to date on this dataset. Full article
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Review
Research Progress on Cordycepin Synthesis and Methods for Enhancement of Cordycepin Production in Cordyceps militaris
Bioengineering 2022, 9(2), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020069 - 11 Feb 2022
Viewed by 817
Abstract
C. militaris is an insect-born fungus that belongs to Ascomycota and Cordyceps. It has a variety of biological activities that can be applied in medicine, health-care products, cosmeceuticals and other fields. Cordycepin (COR) is one of the major bioactive components identified from [...] Read more.
C. militaris is an insect-born fungus that belongs to Ascomycota and Cordyceps. It has a variety of biological activities that can be applied in medicine, health-care products, cosmeceuticals and other fields. Cordycepin (COR) is one of the major bioactive components identified from C. militaris. Thus, C. militaris and COR have attracted extensive attention. In this study, chemical synthetic methods and the biosynthesis pathway of COR were reviewed. As commercially COR was mainly isolated from C. militaris fermentation, the optimizations for liquid and solid fermentation and genetic modifications of C. militaris to increase COR content were also summarized. Moreover, the research progress of genetic modifications of C. militaris and methods for separation and purification COR were introduced. Finally, the existing problems and future research direction of C. militaris were discussed. This study provides a reference for the production of COR in the future. Full article
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Review
Influence of Landing in Neuromuscular Control and Ground Reaction Force with Ankle Instability: A Narrative Review
Bioengineering 2022, 9(2), 68; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020068 - 10 Feb 2022
Viewed by 765
Abstract
Ankle sprains are generally the most common injuries that are frequently experienced by competitive athletes. Ankle sprains, which are the main cause of ankle instability, can impair long-term sports performance and cause chronic ankle instability (CAI). Thus, a comprehensive understanding of the key [...] Read more.
Ankle sprains are generally the most common injuries that are frequently experienced by competitive athletes. Ankle sprains, which are the main cause of ankle instability, can impair long-term sports performance and cause chronic ankle instability (CAI). Thus, a comprehensive understanding of the key factors involved in repeated ankle strains is necessary. During jumping and landing, adaptation to the landing force and control of neuromuscular activation is crucial in maintaining ankle stability. Ankle mobility provides a buffer during landing, and peroneus longus activation inhibits ankle inversion; together, they can effectively minimize the risk of ankle inversion injuries. Accordingly, this study recommends that ankle mobility should be enhanced through active and passive stretching and muscle recruitment training of the peroneus longus muscles for landing strategies should be performed to improve proprioception, which would in turn prevent ankle sprain and injury to neighboring joints. Full article
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Article
An Immersible Microgripper for Pancreatic Islet and Organoid Research
Bioengineering 2022, 9(2), 67; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020067 - 09 Feb 2022
Viewed by 676
Abstract
To improve the predictive value of in vitro experimentation, the use of 3D cell culture models, or organoids, is becoming increasingly popular. However, the current equipment of life science laboratories has been developed to deal with cell monolayers or cell suspensions. To handle [...] Read more.
To improve the predictive value of in vitro experimentation, the use of 3D cell culture models, or organoids, is becoming increasingly popular. However, the current equipment of life science laboratories has been developed to deal with cell monolayers or cell suspensions. To handle 3D cell aggregates and organoids in a well-controlled manner, without causing structural damage or disturbing the function of interest, new instrumentation is needed. In particular, the precise and stable positioning in a cell bath with flow rates sufficient to characterize the kinetic responses to physiological or pharmacological stimuli can be a demanding task. Here, we present data that demonstrate that microgrippers are well suited to this task. The current version is able to work in aqueous solutions and was shown to position isolated pancreatic islets and 3D aggregates of insulin-secreting MIN6-cells. A stable hold required a gripping force of less than 30 μN and did not affect the cellular integrity. It was maintained even with high flow rates of the bath perfusion, and it was precise enough to permit the simultaneous microfluorimetric measurements and membrane potential measurements of the single cells within the islet through the use of patch-clamp electrodes. Full article
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Article
Alginate Core–Shell Capsules for 3D Cultivation of Adipose-Derived Mesenchymal Stem Cells
Bioengineering 2022, 9(2), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020066 - 06 Feb 2022
Viewed by 2260
Abstract
Mesenchymal stem cells (MSCs) are primary candidates in tissue engineering and stem cell therapies due to their intriguing regenerative and immunomodulatory potential. Their ability to self-assemble into three-dimensional (3D) aggregates further improves some of their therapeutic properties, e.g., differentiation potential, secretion of cytokines, [...] Read more.
Mesenchymal stem cells (MSCs) are primary candidates in tissue engineering and stem cell therapies due to their intriguing regenerative and immunomodulatory potential. Their ability to self-assemble into three-dimensional (3D) aggregates further improves some of their therapeutic properties, e.g., differentiation potential, secretion of cytokines, and homing capacity after administration. However, high hydrodynamic shear forces and the resulting mechanical stresses within commercially available dynamic cultivation systems can decrease their regenerative properties. Cells embedded within a polymer matrix, however, lack cell-to-cell interactions found in their physiological environment. Here, we present a “semi scaffold-free” approach to protect the cells from high shear forces by a physical barrier, but still allow formation of a 3D structure with in vivo-like cell-to-cell contacts. We highlight a relatively simple method to create core–shell capsules by inverse gelation. The capsules consist of an outer barrier made from sodium alginate, which allows for nutrient and waste diffusion and an inner compartment for direct cell-cell interactions. Next to capsule characterization, a harvesting procedure was established and viability and proliferation of human adipose-derived MSCs were investigated. In the future, this encapsulation and cultivation technique might be used for MSC-expansion in scalable dynamic bioreactor systems, facilitating downstream procedures, such as cell harvest and differentiation into mature tissue grafts. Full article
(This article belongs to the Special Issue Material and Engineering-Based Approaches for Organoids)
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Review
Role of Implantable Drug Delivery Devices with Dual Platform Capabilities in the Prevention and Treatment of Bacterial Osteomyelitis
Bioengineering 2022, 9(2), 65; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020065 - 06 Feb 2022
Cited by 1 | Viewed by 691
Abstract
As medicine advances and physicians are able to provide patients with innovative solutions, including placement of temporary or permanent medical devices that drastically improve quality of life of the patient, there is the persistent, recurring problem of chronic bacterial infection, including osteomyelitis. Osteomyelitis [...] Read more.
As medicine advances and physicians are able to provide patients with innovative solutions, including placement of temporary or permanent medical devices that drastically improve quality of life of the patient, there is the persistent, recurring problem of chronic bacterial infection, including osteomyelitis. Osteomyelitis can manifest as a result of traumatic or contaminated wounds or implant-associated infections. This bacterial infection can persist as a result of inadequate treatment regimens or the presence of biofilm on implanted medical devices. One strategy to mitigate these concerns is the use of implantable medical devices that simultaneously act as local drug delivery devices (DDDs). This classification of device has the potential to prevent or aid in clearing chronic bacterial infection by delivering effective doses of antibiotics to the area of interest and can be engineered to simultaneously aid in tissue regeneration. This review will provide a background on bacterial infection and current therapies as well as current and prospective implantable DDDs, with a particular emphasis on local DDDs to combat bacterial osteomyelitis. Full article
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Review
N-Acetylglucosamine Sensing and Metabolic Engineering for Attenuating Human and Plant Pathogens
Bioengineering 2022, 9(2), 64; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020064 - 05 Feb 2022
Cited by 1 | Viewed by 694
Abstract
During evolution, both human and plant pathogens have evolved to utilize a diverse range of carbon sources. N-acetylglucosamine (GlcNAc), an amino sugar, is one of the major carbon sources utilized by several human and phytopathogens. GlcNAc regulates the expression of many virulence genes [...] Read more.
During evolution, both human and plant pathogens have evolved to utilize a diverse range of carbon sources. N-acetylglucosamine (GlcNAc), an amino sugar, is one of the major carbon sources utilized by several human and phytopathogens. GlcNAc regulates the expression of many virulence genes of pathogens. In fact, GlcNAc catabolism is also involved in the regulation of virulence and pathogenesis of various human pathogens, including Candida albicans, Vibrio cholerae, Leishmania donovani, Mycobacterium, and phytopathogens such as Magnaporthe oryzae. Moreover, GlcNAc is also a well-known structural component of many bacterial and fungal pathogen cell walls, suggesting its possible role in cell signaling. Over the last few decades, many studies have been performed to study GlcNAc sensing, signaling, and metabolism to better understand the GlcNAc roles in pathogenesis in order to identify new drug targets. In this review, we provide recent insights into GlcNAc-mediated cell signaling and pathogenesis. Further, we describe how the GlcNAc metabolic pathway can be targeted to reduce the pathogens’ virulence in order to control the disease prevalence and crop productivity. Full article
(This article belongs to the Special Issue Bioengineering of Polysaccharide Production Systems)
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Article
Design Strategy for Nanostructured Arrays of Metallodielectric Cuboids to Systematically Tune the Optical Response and Eliminate Spurious Bulk Effects in Plasmonic Biosensors
Bioengineering 2022, 9(2), 63; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020063 - 04 Feb 2022
Cited by 1 | Viewed by 616
Abstract
Plasmonic biosensors are a powerful tool for studying molecule adsorption label-free and with high sensitivity. Here, we present a systematic study on the optical properties of strictly regular nanostructures composed of metallodielectric cuboids with the aim to deliberately tune their optical response and [...] Read more.
Plasmonic biosensors are a powerful tool for studying molecule adsorption label-free and with high sensitivity. Here, we present a systematic study on the optical properties of strictly regular nanostructures composed of metallodielectric cuboids with the aim to deliberately tune their optical response and improve their biosensing performance. In addition, the patterns were tested for their potential to eliminate spurious effects from sensor response, caused by refractive index changes in the bulk solution. Shifts in the plasmonic spectrum are exclusively caused by the adsorbing molecules. For this purpose, nanopatterns of interconnected and separated cubes with dimensions ranging from 150 to 600 nm have been fabricated from poly(methyl methacrylate) using electron-beam lithography followed by metallization with gold. It is shown that a small lateral pattern size, a high aspect ratio, and short connection lengths are favorable to generate extinction spectra with well-separated and pronounced peaks. Furthermore, for selected nanostructures, we have been able to identify reflection angles for which the influence of the bulk refractive index on the position of the plasmonic peaks is negligible. It is shown that sensor operation under these angles enables monitoring of in situ biomolecule adsorption with high sensitivity providing a promising tool for high-throughput applications. Full article
(This article belongs to the Collection Nanoparticles for Therapeutic and Diagnostic Applications)
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Article
Weighted Brain Network Analysis on Different Stages of Clinical Cognitive Decline
Bioengineering 2022, 9(2), 62; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020062 - 04 Feb 2022
Viewed by 717
Abstract
This study addresses brain network analysis over different clinical severity stages of cognitive dysfunction using electroencephalography (EEG). We exploit EEG data of subjective cognitive impairment (SCI) patients, mild cognitive impairment (MCI) patients and Alzheimer’s disease (AD) patients. We propose a new framework to [...] Read more.
This study addresses brain network analysis over different clinical severity stages of cognitive dysfunction using electroencephalography (EEG). We exploit EEG data of subjective cognitive impairment (SCI) patients, mild cognitive impairment (MCI) patients and Alzheimer’s disease (AD) patients. We propose a new framework to study the topological networks with a spatiotemporal entropy measure for estimating the connectivity. Our results show that functional connectivity and graph analysis are frequency-band dependent, and alterations start at the MCI stage. In delta, the SCI group exhibited a decrease of clustering coefficient and an increase of path length compared to MCI and AD. In alpha, the opposite behavior appeared, suggesting a rapid and high efficiency in information transmission across the SCI network. Modularity analysis showed that electrodes of the same brain region were distributed over several modules, and some obtained modules in SCI were extended from anterior to posterior regions. These results demonstrate that the SCI network was more resilient to neuronal damage compared to that of MCI and even more compared to that of AD. Finally, we confirm that MCI is a transitional stage between SCI and AD, with a predominance of high-strength intrinsic connectivity, which may reflect the compensatory response to the neuronal damage occurring early in the disease process. Full article
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Article
Adaptation of a Bacterial Bioluminescent Assay to Monitor Bioeffects of Gold Nanoparticles
Bioengineering 2022, 9(2), 61; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020061 - 03 Feb 2022
Cited by 2 | Viewed by 650
Abstract
Our current study aimed to adapt a bioluminescent bacteria-based bioassay to monitor the bioeffects of gold nanoparticles (AuNPs). Luminous marine bacteria Photobacterium phosphoreum and AuNPs modified with polyvinylpyrrolidone were employed; low-concentration (≤10−3 g/L) bioeffects of AuNPs were studied. Bioluminescence intensity was used [...] Read more.
Our current study aimed to adapt a bioluminescent bacteria-based bioassay to monitor the bioeffects of gold nanoparticles (AuNPs). Luminous marine bacteria Photobacterium phosphoreum and AuNPs modified with polyvinylpyrrolidone were employed; low-concentration (≤10−3 g/L) bioeffects of AuNPs were studied. Bioluminescence intensity was used as an indicator of physiological activity in bacteria. Two additional methods were used: reactive oxygen species (ROS) content was estimated with a chemiluminescent luminol method, and bacterial size was monitored using electron microscopy. The bacterial bioluminescent response to AuNPs corresponded to the “hormesis” model and involved time-dependent bioluminescence activation, as well as a pronounced increase in the number of enlarged bacteria. We found negative correlations between the time courses of bioluminescence and the ROS content in bacterial suspensions, demonstrating the relationship between bioluminescence activation and bacterial ROS consumption. The combined effects of AuNPs and a beta-emitting radionuclide, tritium, revealed suppression of bacterial bioluminescent activity (as compared to their individual effects) and a reduced percentage of enlarged bacteria. Therefore, we demonstrated that our bacteria-based bioluminescence assay is an appropriate tool to study the bioeffects of AuNPs; the bioeffects can be further classified within a unified framework for rapid bioassessment. Full article
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Article
Low-Cost Devices for Three-Dimensional Cell Aggregation, Real-Time Monitoring Microscopy, Microfluidic Immunostaining, and Deconvolution Analysis
Bioengineering 2022, 9(2), 60; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020060 - 03 Feb 2022
Viewed by 514
Abstract
The wide use of 3D-organotypic cell models is imperative for advancing our understanding of basic cell biological mechanisms. For this purpose, easy-to-use enabling technology is required, which should optimally link standardized assessment methods to those used for the formation, cultivation, and evaluation of [...] Read more.
The wide use of 3D-organotypic cell models is imperative for advancing our understanding of basic cell biological mechanisms. For this purpose, easy-to-use enabling technology is required, which should optimally link standardized assessment methods to those used for the formation, cultivation, and evaluation of cell aggregates or primordial tissue. We thus conceived, manufactured, and tested devices which provide the means for cell aggregation and online monitoring within a hanging drop. We then established a workflow for spheroid manipulation and immune phenotyping. This described workflow conserves media and reagent, facilitates the uninterrupted tracking of spheroid formation under various conditions, and enables 3D-marker analysis by means of 3D epifluorescence deconvolution microscopy. We provide a full description of the low-cost manufacturing process for the fluidic devices and microscopic assessment tools, and the detailed blueprints and building instructions are disclosed. Conclusively, the presented compilation of methods and techniques promotes a quick and barrier-free entry into 3D cell biology. Full article
(This article belongs to the Special Issue Analytical Approaches in 3D in vitro Systems)
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Article
Laser-Engraved Liquid Metal Circuit for Wearable Electronics
Bioengineering 2022, 9(2), 59; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020059 - 30 Jan 2022
Viewed by 753
Abstract
Conventional patterning methods for producing liquid metal (LM) electronic circuits, such as the template method, use chemical etching, which requires long cycle times, high costs, and multiple-step operations. In this study, a novel and reliable laser engraving micro-fabrication technology was introduced, which was [...] Read more.
Conventional patterning methods for producing liquid metal (LM) electronic circuits, such as the template method, use chemical etching, which requires long cycle times, high costs, and multiple-step operations. In this study, a novel and reliable laser engraving micro-fabrication technology was introduced, which was used to fabricate personalized patterns of LM electronic circuits. First, by digitizing the pattern, a laser printing technology was used to burn a polyethylene (PE) film, where a polydimethylsiloxane (PDMS) or paper substrate was used to produce grooves. Then, the grooves were filled with LM and the PE film was removed; finally, the metal was packaged with PDMS film. The experimental results showed that the prepared LM could fabricate precise patterned electronic circuits, such as golden serpentine curves and Peano curves. The minimum width and height of the LM circuit were 253 μm and 200 μm, respectively, whereas the printed LM circuit on paper reached a minimum height of 26 μm. This LM flexible circuit could also be adapted to various sensor devices and was successfully applied to heart rate detection. Laser engraving micro-processing technologies could be used to customize various high-resolution LM circuit patterns in a short time, and have broad prospects in the manufacture of flexible electronic equipment. Full article
(This article belongs to the Special Issue Liquid Metal Biomedicine)
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Article
Geometric Parameter Identification of Medical Robot Based on Improved Beetle Antennae Search Algorithm
Bioengineering 2022, 9(2), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020058 - 29 Jan 2022
Cited by 1 | Viewed by 940
Abstract
To improve the accuracy of common intelligent algorithms when identifying the parameters of geometric error in medical robots, this paper proposes an improved beetle antennae search algorithm (RWSAVSBAS). We first establish a model for the kinematic error in medical robots, and then add [...] Read more.
To improve the accuracy of common intelligent algorithms when identifying the parameters of geometric error in medical robots, this paper proposes an improved beetle antennae search algorithm (RWSAVSBAS). We first establish a model for the kinematic error in medical robots, and then add the random wandering behavior of the wolf colony algorithm to the search process of the beetle antennae search algorithm to strengthen its capability for local search. Following this, we improve the global convergence ability of the beetle antennae search algorithm by using the simulated annealing algorithm. We compare the accuracy of end positioning of the proposed algorithm with the frog-jumping algorithm and the beetle antennae search algorithm with variable step length through simulations. The results show that the proposed algorithm has a higher accuracy of convergence, and can significantly improve the accuracy of end positioning of the medical robot. Full article
(This article belongs to the Special Issue Artificial Intelligence Based Computer-Aided Diagnosis)
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Review
Impact of the Process Variables on the Yield of Mesenchymal Stromal Cells from Bone Marrow Aspirate Concentrate
Bioengineering 2022, 9(2), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020057 - 29 Jan 2022
Viewed by 705
Abstract
Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell [...] Read more.
Human bone marrow (BM) has been highlighted as a promising source of mesenchymal stromal cells (MSCs) containing various growth factors and cytokines that can be potentially utilized in regenerative procedures involving cartilage and bone. However, the proportion of MSCs in the nucleated cell population of BM is only around 0.001% to 0.01% thereby making the harvesting and processing technique crucial for obtaining optimal results upon its use in various regenerative processes. Although several studies in the literature have given encouraging results on the utility of BM aspiration concentrate (BMAC) in various regenerative procedures, there is a lack of consensus concerning the harvesting variables such as choice of anesthetic agent to be used, site of harvest, size of the syringe to be used, anticoagulant of choice, and processing variables such as centrifugation time, and speed. In this review article, we aim to discuss the variables in the harvesting and processing technique of BMAC and their impact on the yield of MSCs in the final concentrate obtained from them. Full article
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Article
Design and Evaluation of Engineered Extracellular Vesicle (EV)-Based Targeting for EGFR-Overexpressing Tumor Cells Using Monobody Display
Bioengineering 2022, 9(2), 56; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020056 - 29 Jan 2022
Viewed by 1037
Abstract
Background: Extracellular vesicles (EVs) are attracting interest as a new class of drug delivery vehicles due to their intrinsic nature of biomolecular transport in the body. We previously demonstrated that EV surface modification with tissue-specific molecules accomplished targeted EV-mediated DNA delivery. Methods: Here, [...] Read more.
Background: Extracellular vesicles (EVs) are attracting interest as a new class of drug delivery vehicles due to their intrinsic nature of biomolecular transport in the body. We previously demonstrated that EV surface modification with tissue-specific molecules accomplished targeted EV-mediated DNA delivery. Methods: Here, we describe reliable methods for (i) generating EGFR tumor-targeting EVs via the display of high-affinity monobodies and (ii) in vitro measurement of EV binding using fluorescence and bioluminescence labeling. Monobodies are a well-suited class of small (10 kDa) non-antibody scaffolds derived from the human fibronectin type III (FN3) domain. Results: The recombinant protein consists of the EGFR-targeting monobody fused to the EV-binding domain of lactadherin (C1C2), enabling the monobody displayed on the surface of the EVs. In addition, the use of bioluminescence or fluorescence molecules on the EV surface allows for the assessment of EV binding to the target cells. Conclusions: In this paper, we describe methods of EV engineering to generate targeted delivery vehicles using monobodies that will have diverse applications to furnish future EV therapeutic development, including qualitative and quantitative in vitro evaluation for their binding capacity. Full article
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Article
3D Printing of Abdominal Immobilization Masks for Therapeutics: Dosimetric, Mechanical and Financial Analysis
Bioengineering 2022, 9(2), 55; https://0-doi-org.brum.beds.ac.uk/10.3390/bioengineering9020055 - 29 Jan 2022
Viewed by 774
Abstract
Molding immobilization masks is a time-consuming process, strongly dependent on the healthcare professional, and potentially uncomfortable for the patient. Thus, an alternative sustainable automated production process is proposed for abdominal masks, using fused deposition modelling (FDM) 3D printing with polylactic acid (PLA). Radiological [...] Read more.
Molding immobilization masks is a time-consuming process, strongly dependent on the healthcare professional, and potentially uncomfortable for the patient. Thus, an alternative sustainable automated production process is proposed for abdominal masks, using fused deposition modelling (FDM) 3D printing with polylactic acid (PLA). Radiological properties of PLA were evaluated by submitting a set of PLA plates to photon beam radiation, while estimations of their mechanical characteristics were assessed through numerical simulation. Based on the obtained results, the abdominal mask was 3D printed and process costs and times were analyzed. The plates revealed dose transmissions similar to the conventional mask at all energies, and mechanical deformation guarantees the required immobilization, with a 66% final cost reduction. PLA proved to be an excellent material for this purpose. Despite the increase in labour costs, a significant reduction in material costs is observed with the proposed process. However, the time results are not favorable, mainly due to the printing technique used in this study. Full article
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