Connecting Aortic Stiffness to Vascular Contraction: Does Sex Matter?

This study was designed to connect aortic stiffness to vascular contraction in young male and female Wistar rats. We hypothesized that female animals display reduced intrinsic media-layer stiffness, which associates with improved vascular function. Atomic force microscopy (AFM)-based nanoindentation analysis was used to derive stiffness (Young's modulus) in biaxially (i.e., longitudinal and circumferential) unloaded aortic rings. Reactivity studies compatible with uniaxial loading (i.e., circumferential) were used to assess vascular responses to a selective α1 adrenergic receptor agonist in the presence or absence of extracellular calcium. Elastin and collagen levels were indirectly evaluated with fluorescence microscopy and a picrosirius red staining kit, respectively. We report that male and female Wistar rats display similar AFM-derived aortic media-layer stiffness, even though female animals withstand higher aortic intima-media thickness-to-diameter ratio than males. Female animals also present reduced phenylephrine-induced aortic force development in concentration-response and time-force curves. Specifically, we observed impaired force displacement in both parts of the contraction curve (Aphasic and Atonic) in experiments conducted with and without extracellular calcium. Additionally, collagen levels were lower in female animals without significant elastin content and fragmentation changes. In summary, sex-related functional differences in isolated aortas appear to be related to dissimilarities in the dynamics of vascular reactivity and extracellular matrix composition rather than a direct response to a shift in intrinsic media-layer stiffness.

Comparative study of tapered versus conventional cylindrical balloon for stent implantation in stenotic tapered artery.

The natural tapering of coronary arteries often creates a dilemma for optimal balloon sizing during stenting. The influence of different balloon types, namely, a tapered balloon and a conventional cylindrical balloon, on the mechanical performance of the stent as well as arterial mechanics was investigated via the finite element method. Stent free-expansion and stent deployment in a stenotic tapered artery were investigated numerically. The biomechanical behavior of the two balloon types was compared in terms of stent foreshortening, stent deformation, stent stress distribution, and arterial wall stress distribution. Results indicate that balloon types affect the transient behavior of the stent and the arterial mechanics. Specifically, a tapered balloon could maintain the natural tapering of the coronary artery after stent expansion. In contrast to a cylindrical balloon, tapered balloon also mitigated the foreshortening of the stent (7.69%) as well as the stress concentration in the stent and artery (8.61% and 4.17%, respectively). Hence, tapered balloons should be used in tapered arteries as they may result in low risk of artery injury. This study might provide insights for improved balloon choice and presurgical planning.

Optical Coherence Tomography-Based Modeling of Stent Deployment in Heavily Calcified Coronary Lesion.

In this work, a heavily calcified coronary artery model was reconstructed from optical coherence tomography (OCT) images to investigate the impact of calcification characteristics on stenting outcomes. The calcification was quantified at various cross sections in terms of angle, maximum thickness, and area. The stent deployment procedure, including the crimping, expansion, and recoil, was implemented. The influence of calcification characteristics on stent expansion, malapposition, and lesion mechanics was characterized. Results have shown that the minimal lumen area following stenting occurred at the cross section with the greatest calcification angle. The calcification angle constricted the stretchability of the lesion and thus resulted in a small lumen area. The maximum principal strain and von Mises stress distribution patterns in both the fibrotic tissue and artery were consistent with the calcification profiles. The radially projected region of the calcification tends to have less strain and stress. The peak strain and stress of the fibrotic tissue occurred near the interface with the calcification. It is also the region with a high risk of tissue dissection and strut malapposition. In addition, the superficial calcification with a large angle aggregated the malapposition at the middle of the calcification arc. These detailed mechanistic quantifications could be used to provide a fundamental understanding of the role of calcification in stent expansions, as well as to exploit their potential for enhanced pre- and post-stenting strategies.

Indirect Traumatic Optic Neuropathy Induced by Primary Blast: A Fluid-Structure Interaction Study.

Current knowledge of traumatic ocular injury is still limited as most studies have focused on the ocular injuries that happened at the anterior part of the eye, whereas the damage to the optic nerve known as traumatic optic neuropathy (TON) is poorly understood. The goal of this study is to understand the mechanism of the TON following the primary blast through a fluid-structure interaction model. An axisymmetric three-dimensional (3D) eye model with detailed orbital components was developed to capture the dynamics of the eye under the blast wave. Our numerical results demonstrated a transient pressure elevation in both vitreous and cerebrospinal fluid (CSF). A high strain rate over 100 s-1 was observed throughout the optic nerve during the blast with the most vulnerable part located at the intracanalicular region. The optic nerve deforming at such a high strain rate may account for the axonal damage and vision loss in patients subjected to the primary blast. The results from this work would enhance the understanding of indirect TON and provide guidance in the design of protective eyewear against such injury.

Impact of Calcium Quantifications on Stent Expansions.

Severely calcified plaque is of great concern when planning and implementing a stenting intervention. In this work, computational models were developed to investigate the influence of calcium characteristics on stenting outcomes. The commonly used clinical measurements of calcium (i.e., the arc angle, maximum thickness, length, and volume) were varied to estimate stenting outcomes in terms of lumen gain, stent underexpansion, strut malapposition, and stress or strain distributions of the stenotic lesion. Results have shown that stenting outcomes were most sensitive to the arc angle of the calcium. A thick calcium with a large arc angle resulted in poor stenting outcomes, such as severe stent underexpansion, D-shaped lumen, increased strut malapposition, and large stresses or strains in the plaque. This was attributed to the circumferential stretch of the tissue. Specifically, the noncalcium component was stretched significantly more than the calcium. The circumferential stretch ratios of calcium and noncalcium component were approximately 1.44 and 2.35, respectively, regardless of calcium characteristics. In addition, the peak stress or strain within the artery and noncalcium component of the plaque occurred at the area adjacent to calcium edges (i.e., the interface between the calcium and the noncalcium component) coincident with the location of peak malapposition. It is worth noting that calcium played a protective role for the artery underneath, which was at the expense of the overstretch and stress concentrations in the other portion of the artery. These detailed mechanistic quantifications could be used to provide a fundamental understanding of the impact of calcium quantifications on stent expansions, as well as to exploit their potential for a better preclinical strategy.

Intracranial Pressure Influences the Behavior of the Optic Nerve Head.

In this work, the biomechanical responses of the optic nerve head (ONH) to acute elevations in intracranial pressure (ICP) were systematically investigated through numerical modeling. An orthogonal experimental design was developed to quantify the influence of ten input factors that govern the anatomy and material properties of the ONH on the peak maximum principal strain (MPS) in the lamina cribrosa (LC) and postlaminar neural tissue (PLNT). Results showed that the sensitivity of ONH responses to various input factors was region-specific. In the LC, the peak MPS was most strongly dependent on the sclera thickness, LC modulus, and scleral canal size, whereas in the PLNT, the peak MPS was more sensitive to the scleral canal size, neural tissue modulus, and pia mater modulus. The enforcement of clinically relevant ICP in the retro-orbital subarachnoid space influenced the sensitivity analysis. It also induced much larger strains in the PLNT than in the LC. Moreover, acute elevation of ICP leads to dramatic strain distribution changes in the PLNT, but had minimal impact on the LC. This work could help to better understand patient-specific responses, to provide guidance on biomechanical factors resulting in optic nerve diseases, such as glaucoma, papilledema, and ischemic optic neuropathy, and to illuminate the possibilities for exploiting their potential to treat and prevent ONH diseases.

Implementation and validation of aortic remodeling in hypertensive rats.

A computational framework was implemented and validated to better understand the hypertensive artery remodeling in both geometric dimensions and material properties. Integrating the stress-modulated remodeling equations into commercial finite element codes allows a better control and visualization of local mechanical parameters. Both arterial thickening and stiffening effects were captured and visualized. An adaptive material remodeling strategy combined with the element birth and death techniques for the geometrical growth were implemented. The numerically predicted remodeling results in terms of the wall thickness, inner diameter, and the ratio of elastin to collagen content of the artery were compared with and fine-tuned by the experimental data from a documented rat model. The influence of time constant on the material remodeling was also evaluated and discussed. In addition, the geometrical growth and material remodeling were isolated to better understand the contributions of each element to the arterial remodeling and their coupling effect. Finally, this framework was applied to an image-based 3D artery generated from computer tomography to demonstrate its heterogeneous remodeling process. Results suggested that hypertension induced arterial remodeling are quite heterogeneous due to both nonlinear geometry and material adaptation process. The developed computational model provided more insights into the evolutions of morphology and material of the artery, which could complement the discrete experimental data for improving the clinical management of hypertension. The proposed framework could also be extended to study other types of stress-driven tissue remodeling including in-stent restenosis and grafting.

Quantifying the efficacy of protective eyewear in pediatric soccer-induced retinal injury.

BACKGROUND: Ocular injury is common in children playing sports. Sports-related eye injuries, if severe enough, can lead to permanent vision impairment. Soccer, the most popular sport in the world, is a sport in which players rarely use protective eyewear. The purpose of this study was to determine how eye injuries are induced by a soccer ball impact and to evaluate whether eye protection influences the effects of impact. METHODS: A finite element (FE) computer simulation was used to simulate soccer ball trauma on a model of the eye with and without eye protection. Protective eyewear of different materials (polycarbonate and acrylic) was modeled to investigate the optimal medium for eye protection. Stress and strain experienced by the eyeball was quantified by the FE computer simulation in each model. RESULTS: Protective eyewear was found to be effective in lowering ocular stress and strain by absorbing and redirecting energy from the ball. Compared to the unprotected eye model, polycarbonate eyewear reduced the average stress the retina experienced by 61%, whereas the acrylic model reduced the average stress by 40%. Polycarbonate and acrylic eyewear also reduced the maximum strain experienced by the retina by 69% and 47%, respectively, reducing the severity of deformations of the eye on impact. CONCLUSIONS: These findings suggest that wearing protective eyewear, especially when made of polycarbonate, can be an effective means of reducing injury-inducing retinal stress. The use of eye protection is thus recommended for pediatric patients participating in soccer.

The role of intrapartum fetal head compression in neonatal retinal hemorrhage.

PURPOSE: Neonatal retinal hemorrhage is a common finding in newborns, but the underlying mechanisms are not fully understood. A computational simulation was designed to study the events taking place in the eye and orbit when the head is compressed as the neonate passes through the birth canal. METHODS: A finite element model of the eye, optic nerve sheath, and orbit was simulated and subjected to forces mimicking rises in intracranial pressure (ICP) associated with maternal contractions during normal vaginal delivery. Resulting changes in intraocular pressure (IOP), pressure in the optic nerve sheath, and stress within the sclera and retina were measured. RESULTS: During contractions, increased ICP was transmitted to the orbit, globe, and optic nerve sheath. IOP rose by 2.71 kPa near the posterior pole. Pressure at the center of the optic nerve sheath rose by 7.31 kPa and up to 9.30 kPa at its interface with the sclera. Stress in the retina was highest near the optic disk and reached 10.93, 10.99, and 13.28 kPa in the preretinal, intraretinal, and subretinal layers, respectively. Stress in the sclera peaked at 12.76 kPa. CONCLUSIONS: Increasing ICP associated with natural vaginal delivery increases intraorbital pressure, which applies stress to the retina. Associated retinal deformation may cause tearing of the retinal vasculature. Increased pressure within the optic nerve sheath may occlude the central retinal vein, resulting in outflow obstruction and subsequent rupture. Forces accumulated near the optic disk, likely accounting for the tendency of neonatal retinal hemorrhage to occur posteriorly.

Load-sharing characteristics of stenting and post-dilation in heavily calcified coronary artery.

In this work, stenting in non-calcified and heavily calcified coronary arteries was quantified in terms of diameter-pressure relationships and load transfer from the balloon to the artery. The efficacy of post-dilation in non-calcified and heavily calcified coronary arteries was also characterized in terms of load sharing and the changes in tissue mechanics. Our results have shown that stent expansion exhibits a cylindrical shape in non-calcified lesions, while it exhibits a dog bone shape in heavily calcified lesions. Load-sharing analysis has shown that only a small portion of the pressure load (1.4 N, 0.8% of total pressure load) was transferred to the non-calcified lesion, while a large amount of the pressure load (19 N, 12%) was transferred to the heavily calcified lesion. In addition, the increasing inflation pressure (from 10 to 20 atm) can effectively increase the minimal lumen diameter (from 1.48 mm to 2.82 mm) of the heavily calcified lesion, the stress (from 1.5 MPa to 8.4 MPa) the strain energy in the calcification (1.77 mJ to 26.5 mJ), which associated with the potential of calcification fracture. Results indicated that increasing inflation pressure can be an effective way to improve the stent expansion if a dog bone shape of the stenting profile is observed. Considering the risk of a balloon burst, our results support the design and application of the high-pressure balloon for post-dilation.

Load-sharing characteristics of stenting and post-dilation in heavily calcified coronary artery.

In this work, stenting in non-calcified and heavily calcified coronary arteries was quantified in terms of diameter-pressure relationships and load transfer from the balloon to the artery. The efficacy of post-dilation in non-calcified and heavily calcified coronary arteries was also characterized in terms of load sharing and the changes in tissue mechanics. Our results have shown that stent expansion exhibits a cylindrical shape in non-calcified lesions, while it exhibits a dog bone shape in heavily calcified lesions. Load-sharing analysis has shown that only a small portion of the pressure load (1.4 N, 0.8% of total pressure load) was transferred to the non-calcified lesion, while a large amount of the pressure load (19 N, 12%) was transferred to the heavily calcified lesion. In addition, the increasing inflation pressure (from 10 to 20 atm) can effectively increase the minimal lumen diameter (from 1.48 to 2.82 mm) of the heavily calcified lesion, the stress (from 1.5 to 8.4 MPa) and the strain energy in the calcification (1.77 mJ to 26.5 mJ), which are associated with the potential of calcification fracture. Results indicated that increasing inflation pressure can be an effective way to improve the stent expansion if a dog bone shape of the stenting profile is observed. Considering the risk of a balloon burst, our results support the design and application of the high-pressure balloon for post-dilation. This work also sheds some light on the stent design and choice of stent materials for improving the stent expansion at the dog bone region and mitigating stresses on arterial tissues.

Prediction of stent under-expansion in calcified coronary arteries using machine learning on intravascular optical coherence tomography images.

It can be difficult/impossible to fully expand a coronary artery stent in a heavily calcified coronary artery lesion. Under-expanded stents are linked to later complications. Here we used machine/deep learning to analyze calcifications in pre-stent intravascular optical coherence tomography (IVOCT) images and predicted the success of vessel expansion. Pre- and post-stent IVOCT image data were obtained from 110 coronary lesions. Lumen and calcifications in pre-stent images were segmented using deep learning, and lesion features were extracted. We analyzed stent expansion along the lesion, enabling frame, segmental, and whole-lesion analyses. We trained regression models to predict the post-stent lumen area and then computed the stent expansion index (SEI). Best performance (root-mean-square-error = 0.04 ± 0.02 mm2, r = 0.94 ± 0.04, p < 0.0001) was achieved when we used features from both lumen and calcification to train a Gaussian regression model for segmental analysis of 31 frames in length. Stents with minimum SEI > 80% were classified as "well-expanded;" others were "under-expanded." Under-expansion classification results (e.g., AUC = 0.85 ± 0.02) were significantly improved over a previous, simple calculation, as well as other machine learning solutions. Promising results suggest that such methods can identify lesions at risk of under-expansion that would be candidates for intervention lesion preparation (e.g., atherectomy).

On the importance of modeling stent procedure for predicting arterial mechanics.

The stent-artery interactions have been increasingly studied using the finite element method for better understanding of the biomechanical environment changes on the artery and its implications. However, the deployment of balloon-expandable stents was generally simplified without considering the balloon-stent interactions, the initial crimping process of the stent, its overexpansion routinely used in the clinical practice, or its recoil process. In this work, the stenting procedure was mimicked by incorporating all the above-mentioned simplifications. The impact of various simplifications on the stent-induced arterial stresses was systematically investigated. The plastic strain history of stent and its resulted geometrical variations, as well as arterial mechanics were quantified and compared. Results showed the model without considering the stent crimping process underestimating the minimum stent diameter by 17.2%, and overestimating the maximum radial recoil by 144%. It was also suggested that overexpansion resulted in a larger stent diameter, but a greater radial recoil ratio and larger intimal area with high stress were also obtained along with the increase in degree of overexpansion.

Performance of self-expanding nitinol stent in a curved artery: impact of stent length and deployment orientation.

The primary aim of this work was to investigate the performance of self-expanding Nitinol stents in a curved artery through finite element analysis. The interaction between a PROTÉGÉ™ GPS™ self-expanding Nitinol stent and a stenosed artery, as well as a sheath, was characterized in terms of acute lumen gain, stent underexpansion, incomplete stent apposition, and tissue prolapse. The clinical implications of these parameters were discussed. The impact of stent deployment orientation and the stent length on the arterial wall stress distribution were evaluated. It was found that the maximum principal stress increased by 17.46%, when the deployment orientation of stent was varied at a 5 deg angle. A longer stent led to an increased contact pressure between stent and underlying tissue, which might alleviate the stent migration. However, it also caused a severe hinge effect and arterial stress concentration correspondingly, which might aggravate neointimal hyperplasia. The fundamental understanding of the behavior of a self-expanding stent and its clinical implications will facilitate a better device design.

Rapid Prediction of Retina Stress and Strain Patterns in Soccer-Related Ocular Injury: Integrating Finite Element Analysis with Machine Learning Approach.

Soccer-related ocular injuries, especially retinal injuries, have attracted increasing attention. The mechanics of a flying soccer ball have induced abnormally higher retinal stresses and strains, and their correlation with retinal injuries has been characterized using the finite element (FE) method. However, FE simulations demand solid mechanical expertise and extensive computational time, both of which are difficult to adopt in clinical settings. This study proposes a framework that combines FE analysis with a machine learning (ML) approach for the fast prediction of retina mechanics. Different impact scenarios were simulated using the FE method to obtain the von Mises stress map and the maximum principal strain map in the posterior retina. These stress and strain patterns, along with their input parameters, were used to train and test a partial least squares regression (PLSR) model to predict the soccer-induced retina stress and strain in terms of distributions and peak magnitudes. The peak von Mises stress and maximum principal strain prediction errors were 3.03% and 9.94% for the frontal impact and were 9.08% and 16.40% for the diagonal impact, respectively. The average prediction error of von Mises stress and the maximum principal strain were 15.62% and 21.15% for frontal impacts and were 10.77% and 21.78% for diagonal impacts, respectively. This work provides a surrogate model of FE analysis for the fast prediction of the dynamic mechanics of the retina in response to the soccer impact, which could be further utilized for developing a diagnostic tool for soccer-related ocular trauma.

Exploring the Vitreoretinal Interface: A Key Instigator of Unique Retinal Hemorrhage Patterns in Pediatric Head Trauma.

PURPOSE: Various types of trauma can cause retinal hemorrhages in children, including accidental and nonaccidental head trauma. We used animal eyes and a finite element model of the eye to examine stress patterns produced during purely linear and angular accelerations, along with stresses attained during simulated repetitive shaking of an infant. METHODS: Using sheep and primate eyes, sclerotomy windows were created by removing the sclera, choroid, and retinal pigment epithelium to expose the retina. A nanofiber square was glued to a 5 mm2 area of retina. The square was pulled and separated from vitreous while force was measured. A finite element model of the pediatric eye was used to computationally measure tension stresses during shaking. RESULTS: In both sheep and primate eyes, tension stress required for separation of retina from vitreous range from 1 to 5 kPa. Tension stress generated at the vitreoretinal interface predicted by the computer simulation ranged from 3 to 16 kPa during a cycle of shaking. Linear acceleration generated lower tension stress than angular acceleration. Angular acceleration generated maximal tension stress along the retinal vasculature. Linear acceleration produced more diffuse force distribution centered at the poster pole. CONCLUSIONS: The finite element model predicted that tension stress attained at the retina during forcible shaking of an eye can exceed the minimum threshold needed to produce vitreoretinal separation as measured in animal eyes. Furthermore, the results show that movements that involve significant angular acceleration produce strong stresses localized along the vasculature, whereas linear acceleration produces weaker, more diffuse stress centered towards the posterior pole of the eye.

Upper Airway Flow Dynamics in Obstructive Sleep Apnea Patients with Various Apnea-Hypopnea Index.

BACKGROUND AND AIM: This study evaluates the upper airway flow characteristics, anatomical features and analyzes their correlations with AHI in patients with varied degrees of OSA severity seeking for discernments of the underlying pathophysiological profile. MATERIALS AND METHODS: Patient-specific computational fluid dynamics models were reconstructed from high-resolution cone-beam computed tomography images for 4 OSA patients classified as minimal, mild, moderate, and severe according to AHI. RESULTS: The parameters, minimal cross-sectional area (MCA), and the pharyngeal airway volume did not show clear correlations with the OSA severity defined according to AHI. No correlations were found between the classically defined resistance of the airway in terms of pressure drop and AHI. The flow analysis further showed that the fluid mechanisms likely to cause airway collapse are associated with the degree of narrowing in the pharyngeal airway rather than AHI. Results also suggested that some patients classified as severe OSA according to the AHI can show less susceptibility to airway collapse than patients with relatively lower AHI values and vice versa. CONCLUSIONS: The relative contribution of anatomical and non-anatomical causes to the OSA severity can significantly vary between patients. AHI alone is inadequate to be used as a marker of the pathophysiological profile of OSA. Combining airflow analysis with AHI in diagnosing OSA severity may provide additional details about the underlying pathophysiology, subsequently improving the individualized clinical outcomes.

Finite Element Analysis of Soccer Ball-Related Ocular and Retinal Trauma and Comparison with Abusive Head Trauma.

Purpose: Trauma to the eye resulting from a soccer ball is a common sports-related injury. Although the types of ocular pathologic features that result from impact have been documented, the underlying pathophysiologic mechanics are not as well studied. The purpose of this study was to evaluate the biomechanical events after the collision of a soccer ball with the eye to better understand the pathophysiology of observed ocular and retinal injuries and to compare them with those observed in abusive head trauma (AHT). Design: Computer simulation study. Participants: None. Methods: A finite element model of the eye was used to investigate the effects of a collision of a soccer ball on the eye. Main Outcome Measures: Intraocular pressure and stress. Results: Impact of the soccer ball with the eye generated a pressure wave that traveled through the vitreous, creating transient pockets of high and negative pressure. During the high-frequency phase, pressure in the vitreous near the posterior pole ranged from 39.6 to -30.9 kPa. Stress in ocular tissue was greatest near the point of contact, with a peak of 66.6 kPa. The retina experienced the greatest stress at the vasculature, especially at distal branches, where stress rose to 15.4 kPa. On average, retinal stress was greatest in the subretinal layer, but was highest in the preretinal layer when considering only vascular tissue. Conclusions: The high intraocular pressure and stress in ocular tissue near the point of soccer ball impact suggest that injuries to the anterior segment of the eye can be attributed to direct transmission of force from the ball. The subsequent propagation of a pressure wave may cause injuries to the posterior segment as the positive and negative pressures exert compressive and tractional forces on the retina. The linear movement of the pressure wave likely accounts for localization of retinal lesions to the posterior pole or superior temporal quadrant. The primarily linear force in soccer ball trauma is the probable cause for the more localized injury profile and lower retinal hemorrhage incidence compared with AHT, in which repetitive angular force is also at play.

An asynchronous artifact-enhanced electroencephalogram based control paradigm assisted by slight facial expression.

In this study, an asynchronous artifact-enhanced electroencephalogram (EEG)-based control paradigm assisted by slight-facial expressions (sFE-paradigm) was developed. The brain connectivity analysis was conducted to reveal the dynamic directional interactions among brain regions under sFE-paradigm. The component analysis was applied to estimate the dominant components of sFE-EEG and guide the signal processing. Enhanced by the artifact within the detected electroencephalogram (EEG), the sFE-paradigm focused on the mainstream defect as the insufficiency of real-time capability, asynchronous logic, and robustness. The core algorithm contained four steps, including "obvious non-sFE-EEGs exclusion," "interface 'ON' detection," "sFE-EEGs real-time decoding," and "validity judgment." It provided the asynchronous function, decoded eight instructions from the latest 100 ms signal, and greatly reduced the frequent misoperation. In the offline assessment, the sFE-paradigm achieved 96.46% ± 1.07 accuracy for interface "ON" detection and 92.68% ± 1.21 for sFE-EEGs real-time decoding, with the theoretical output timespan less than 200 ms. This sFE-paradigm was applied to two online manipulations for evaluating stability and agility. In "object-moving with a robotic arm," the averaged intersection-over-union was 60.03 ± 11.53%. In "water-pouring with a prosthetic hand," the average water volume was 202.5 ± 7.0 ml. During online, the sFE-paradigm performed no significant difference (P = 0.6521 and P = 0.7931) with commercial control methods (i.e., FlexPendant and Joystick), indicating a similar level of controllability and agility. This study demonstrated the capability of sFE-paradigm, enabling a novel solution to the non-invasive EEG-based control in real-world challenges.

Optimization of Freeze-FRESH Methodology for 3D Printing of Microporous Collagen Constructs.

Freeform reversible embedding of suspended hydrogels (FRESH) is a layer-by-layer extrusion-based technique to enable three-dimensional (3D) printing of soft tissue constructs by using a thermo-reversible gelatin support bath. Suboptimal resolution of extrusion-based printing limits its use for the creation of microscopic features in the 3D construct. These microscopic features (e.g., pore size) are known to have a profound effect on cell migration, cell-cell interaction, proliferation, and differentiation. In a recent study, FRESH-based 3D printing was combined with freeze-casting in the Freeze-FRESH (FF) method, which yielded alginate constructs with hierarchical porosity. However, use of the FF approach allowed little control of micropore size in the printed alginate constructs. Herein, the FF methodology was optimized for 3D printing of collagen constructs with greater control of microporosity. Modifications to the FF method entailed melting of the FRESH bath before freezing to allow more efficient heat transport, achieve greater control on microporosity, and permit polymerization of collagen molecules to enable 3D printing of stable microporous collagen constructs. The effects of different freezing temperatures on microporosity and physical properties of the 3D-printed collagen constructs were assessed. In addition, finite element (FE) models were generated to predict the mechanical properties of the microporous constructs. Further, the impact of different micropore sizes on cellular response was evaluated. Results showed that the microporosity of 3D-printed collagen constructs can be tailored by customizing the FF approach. Compressive modulus of microporous constructs was significantly lower than the non-porous control, and the FE model verified these findings. Constructs with larger micropore size were more stable and showed significantly greater cell infiltration and metabolic activity. Together, these results suggest that the FF method can be customized to guide the design of 3D-printed microporous collagen constructs.