Bioengineering最新文献

More than three decades ago, we embarked on a number of bioengineering explorations using the most advanced materials and fabrication methods. In every area we ventured into, it was our intention to ensure fundamental discoveries were deployed into the clinic to benefit patients. When we embarked on this journey, we did so without a road map, not even a compass, and so the path was arduous, sometimes tedious. Now, we can see the doorway to deployment on the near horizon. We now appreciate that overcoming the challenges has made this a rewarding and exciting journey. However, maybe we could have been here a lot sooner, and so maybe the lessons we have learned could benefit others and accelerate progress in clinical translation. Through a number of case studies, including neural regeneration, cartilage regeneration, skin regeneration, the 3D printing of capsules for islet cell transplantation, and the bioengineered cornea, here, we retrace our steps. We will summarise the journey to date, point out the obstacles encountered, and celebrate the translational impact. Then, we will provide a framework for project design with the clinical deployment of bioengineered products as the goal.

(1) Background: The kinematic characteristics of disc prosthesis undergoing complex motion are not well understood. Therefore, examining complex motion may provide an improved understanding of the post-operative behavior of spinal implants. (2) Methods: The aim of this study was to develop kinematic tests that simulate multiplanar motion and combined rotational-translational motion in a disc prosthesis. In this context, five generic zirconia-toughened alumina (BIOLOX^®delta, CeramTec, Germany) ball and socket samples were tested in a 6 DOF spine simulator under displacement control with an axial compressive force of 100 N in five motion modes: (1) flexion-extension (FE = ± 7.5°), (2) lateral bending (LB = ± 6°), (3) combined FE-LB (4) combined FE and anteroposterior translation (AP = 3 mm), and (5) combined LB and lateral motion (3 mm). For combined rotational-translational motion, two scenarios were analyzed: excessive translational movement after sample rotation (scenario 1) and excessive translational movement during rotation (scenario 2). (3) Results: For combined FE-LB, the resultant forces and moments were higher compared to the unidirectional motion modes. For combined rotational-translational motion (scenario 1), subluxation occurred at FE = 7.5° with an incremental increase in AP translation = 1.49 ± 0.18 mm, and LB = 6° with an incremental increase of lateral translation = 2.22 ± 0.16 mm. At the subluxation point, the incremental increase in AP force and lateral force were 30.4 ± 3.14 N and 40.8 ± 2.56 N in FE and LB, respectively, compared to the forces at the same angles during unidirectional motion. For scenario 2, subluxation occurred at FE = 4.93° with an incremental increase in AP translation = 1.75 mm, and LB = 4.52° with an incremental increase in lateral translation = 1.99 mm. At the subluxation point, the incremental increase in AP force and lateral force were 39.17 N and 38.94 N in FE and LB, respectively, compared to the forces in the same angles during the unidirectional motion. (4) Conclusions: The new test protocols improved the understanding of in vivo-like behavior from in vitro testing. Simultaneous translation-rotation motion was shown to provoke subluxation at lower motion extents. Following further validation of the proposed complex motion testing, these new methods can be applied future development and characterization of spinal motion-preserving implants.

The detection of contrast-enhancing lesions (CELs) is fundamental for the diagnosis and monitoring of patients with multiple sclerosis (MS). This task is time-consuming and suffers from high intra- and inter-rater variability in clinical practice. However, only a few studies proposed automatic approaches for CEL detection. This study aimed to develop a deep learning model that automatically detects and segments CELs in clinical Magnetic Resonance Imaging (MRI) scans. A 3D UNet-based network was trained with clinical MRI from the Swiss Multiple Sclerosis Cohort. The dataset comprised 372 scans from 280 MS patients: 162 showed at least one CEL, while 118 showed no CELs. The input dataset consisted of T1-weighted before and after gadolinium injection, and FLuid Attenuated Inversion Recovery images. The sampling strategy was based on a white matter lesion mask to confirm the existence of real contrast-enhancing lesions. To overcome the dataset imbalance, a weighted loss function was implemented. The Dice Score Coefficient and True Positive and False Positive Rates were 0.76, 0.93, and 0.02, respectively. Based on these results, the model developed in this study might well be considered for clinical decision support.

Background: Our study addresses the lack of consensus on measuring leg length discrepancy (LLD) after total hip arthroplasty (THA). We will assess the inter-observer variability and correlation between the five most commonly used LLD methods and investigate the use of trigonometric principles in overcoming the limitations of current techniques.

Methods: LLD was measured on postoperative AP pelvic radiographs using five conventional methods. CT images created a 3D computer model of the pelvis and femur. The resulting models were projected onto a 2D, used to measure LLD by the five methods. The measurements were evaluated via Taguchi analysis, a statistical method identifying the process's most influential factors. The approach was used to assess the new trigonometric method.

Results: Conventional methods demonstrated poor correlation. Methods referenced to the centers of the femoral heads were insensitive to LLD originating outside the acetabular cup. Methods referencing either the inter-ischial line or the inter-obturator foramina to the lesser trochanter were sensitive to acetabular and femoral components. Trigonometry-based measurements showed a higher correlation.

Conclusions: Our results underscore clinicians' need to specify the methods used to assess LLD. Applying trigonometric principles was shown to be accurate and reliable, but it was contingent on proper radiographic alignment.

Antimicrobial peptides (AMPs) are considered a promising alternative to conventional antibiotics to fight against the rapid evolution of antibiotic resistance. Other than their potent antimicrobial properties, AMP-based vesicles can be used as efficient drug-delivery vehicles. In the present study, we synthesized and characterized a new cyclic AMP, consisting of all-hydrophobic cores with antimicrobial activity against S. aureus. Interestingly, CycP undergoes supramolecular self-assembly, and self-assembled CycP (sCycP) vesicles are characterized under an electron microscope; however, these vesicles do not display antimicrobial activity. Next, sCycP vesicles are used in combination with SXT (sulfamethoxazole-trimethoprim) vesicles to check the drug loading and delivery capacity of sCycP vesicles to bacterial cell membranes. Interestingly, sCycP vesicles showed synergistic action with SXT vesicles and resulted in a significant reduction in MIC against S. aureus. Further, electron microscopy confirmed the membrane-specific killing mechanism of SXT-loaded sCycP vesicles. Additionally, CycP showed high binding affinities with the β-lactamase of S. aureus, which was one of its possible antimicrobial mechanisms of action. Overall, the results suggested that CycP is a novel self-assembled dual-action cyclic AMP with non-cytotoxic properties that can be used alone as an AMP or a self-assembled drug delivery vehicle for antibiotics to combat S. aureus infections.

Cultivated meat, an advancement in cellular agriculture, holds promise in addressing environmental, ethical, and health challenges associated with traditional meat production. Utilizing tissue engineering principles, cultivated meat production employs biomaterials and technologies to create cell-based structures by introducing cells into a biocompatible scaffold, mimicking tissue organization. Among the cell sources used for producing muscle-like tissue for cultivated meats, primary adult stem cells like muscle satellite cells exhibit robust capabilities for proliferation and differentiation into myocytes, presenting a promising avenue for cultivated meat production. Evolutionarily optimized for growth in a 3D microenvironment, these cells benefit from the biochemical and biophysical cues provided by the extracellular matrix (ECM), regulating cell organization, interactions, and behavior. While plant protein-based scaffolds have been explored for their utilization for cultivated meat, they lack the biological cues for animal cells unless functionalized. Conversely, a decellularized bovine placental tissue ECM, processed from discarded birth tissue, achieves the biological functionalities of animal tissue ECM without harming animals. In this study, collagen and total ECM were prepared from decellularized bovine placental tissues. The collagen content was determined to be approximately 70% and 40% in isolated collagen and ECM, respectively. The resulting porous scaffolds, crosslinked through a dehydrothermal (DHT) crosslinking method without chemical crosslinking agents, supported the growth of bovine myoblasts. ECM scaffolds exhibited superior compatibility and stability compared to collagen scaffolds. In an attempt to make cultivate meat constructs, bovine myoblasts were cultured in steak-shaped ECM scaffolds for about 50 days. The resulting construct not only resembled muscle tissues but also displayed high cellularity with indications of myogenic differentiation. Furthermore, the meat constructs were cookable and able to sustain the grilling/frying. Our study is the first to utilize a unique bovine placentome-derived ECM scaffold to create a muscle tissue-like meat construct, demonstrating a promising and sustainable option for cultivated meat production.

The purpose of this study was to assess the biomechanical adaptations prompted by stationary cycling paired with visual feedback of vertical pedal reaction forces during both stationary cycling and overground walking for patients who underwent a total knee arthroplasty (TKA). Specifically, an emphasis on the inter-limb deficits in knee joint biomechanics were examined. Ten patients who underwent a TKA took part in an acute intervention with pre- and post-testing measurements of kinematics (240 Hz) and kinetics (1200 Hz) during stationary cycling and overground walking. The intervention phase consisted of six cycling sessions during which participants were provided with visual feedback of their bilateral peak vertical pedal reaction force, with instructions to maintain a symmetrical loading between limbs. A 2 × 2 (work rate/speed × time) repeated measures ANOVA (α = 0.05) was conducted on key outcome variables. Peak knee extension moment asymmetry during stationary cycling significantly improved (p = 0.038, η²_p = 0.610) following the acute intervention. Walking velocities for both preferred (p = 0.001, d = 0.583) and fast (p = 0.002, d = 0.613) walking speeds displayed improvements from pre- to post-testing. Significant improvements in the total score (p = 0.009, d = 0.492) and ADL subscale score (p = 0.041, d = 0.270) for the Knee Injury and Osteoarthritis Outcome Score were present following the acute intervention. Stationary cycling with visual feedback may be beneficial post-TKA; however, further investigation is merited.

The fallopian tubes are essential for human fertility, facilitating the movement of sperm and oocytes to the fertilization site and transporting fertilized oocytes to the uterus. Infertility can result from changes in the fallopian tubes due to tubal endometriosis and women's aging. In this study, we modeled human fallopian tubes with and without endometriosis for different women's age groups to evaluate the chances of normal sperm cells reaching the fertilization site and oocytes arriving at the uterine cavity. For this purpose, we employed a distinctive combination of simulation tools to develop a dynamic three-dimensional (3D) model of normal human sperm cells and oocytes swimming inside normal and endometriosis-affected human fallopian tubes for different women's group ages. We observed that in tubal endometriosis cases, fewer sperm cells reach the fertilization site and more oocytes become trapped in the tube walls compared to normal tubes. Additionally, aging decreases the number of sperm cells and oocytes reaching the fertilization site in normal and endometriosis-affected tubes. Our model evaluates the mechanisms of sperm and oocyte behaviors due to women's aging and fallopian tube issues caused by endometriosis, presenting new avenues for developing diagnostic and treatment tools for tubal endometriosis and age-related infertility issues.

Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here, we introduce a novel post-processing algorithm called 3D quantitative amplified MRI (3D q-aMRI). This algorithm enables the visualization and quantification of pulsatile brain motion. 3D q-aMRI was validated and optimized on a 3D digital phantom and was applied in vivo on healthy volunteers for its ability to accurately measure brain parenchyma and CSF voxel displacement. Simulation results show that 3D q-aMRI can accurately quantify sub-voxel motions in the order of 0.01 of a voxel size. The algorithm hyperparameters were optimized and tested on in vivo data. The repeatability and reproducibility of 3D q-aMRI were shown on six healthy volunteers. The voxel displacement field extracted by 3D q-aMRI is highly correlated with the displacement measurements estimated by phase contrast (PC) MRI. In addition, the voxel displacement profile through the cerebral aqueduct resembled the CSF flow profile reported in previous literature. Differences in brain motion was observed in patients with dementia compared with age-matched healthy controls. In summary, 3D q-aMRI is a promising new technique that can both visualize and quantify pulsatile brain motion. Its ability to accurately quantify sub-voxel motion in physical units holds potential for the assessment of pulsatile brain motion as well as the indirect assessment of CSF homeostasis. While further research is warranted, 3D q-aMRI may provide important diagnostic information for neurological disorders such as Alzheimer's disease.

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