Annals of Biomedical Engineering

The coordinated biomechanical performance, such as uterine stretch and cervical barrier function, within maternal reproductive tissues facilitates healthy human pregnancy and birth. Quantifying normal biomechanical function and detecting potentially detrimental biomechanical dysfunction (e.g., cervical insufficiency, uterine overdistention, premature rupture of membranes) is difficult, largely due to minimal data on the shape and size of maternal anatomy and material properties of tissue across gestation. This study quantitates key structural features of human pregnancy to fill this knowledge gap and facilitate three-dimensional modeling for biomechanical pregnancy simulations to deeply explore pregnancy and childbirth. These measurements include the longitudinal assessment of uterine and cervical dimensions, fetal weight, and cervical stiffness in 47 low-risk pregnancies at four time points during gestation (late first, middle second, late second, and middle third trimesters). The uterine and cervical size were measured via 2-dimensional ultrasound, and cervical stiffness was measured via cervical aspiration. Trends in uterine and cervical measurements were assessed as time-course slopes across pregnancy and between gestational time points, accounting for specific participants. Patient-specific computational solid models of the uterus and cervix, generated from the ultrasonic measurements, were used to estimate deformed uterocervical volume. Results show that for this low-risk cohort, the uterus grows fastest in the inferior-superior direction from the late first to middle second trimester and fastest in the anterior-posterior and left-right direction between the middle and late second trimester. Contemporaneously, the cervix softens and shortens. It softens fastest from the late first to the middle second trimester and shortens fastest between the late second and middle third trimester. Alongside the fetal weight estimated from ultrasonic measurements, this work presents holistic maternal and fetal patient-specific biomechanical measurements across gestation.

BackgroundConventional left ventricular assist device ramp metrics are load dependent, obscuring intrinsic myocardial recovery. A mechanistic, patient-specific representation of ventricular mechanics, identifiable from routine clinical data, could provide quantitative indices of intrinsic left ventricular (LV) function for longitudinal recovery surveillance. ObjectiveTo develop and verify a ramp-integrated, patient-specific model of HeartMate 3-assisted LV function that can yield indices of intrinsic myocardial contractility and remodeling. MethodsWe represented LV pressure-volume (PV) behavior with a PV envelope composed of a monotonic passive PV relation (pPVR) and a unimodal active PV relation (aPVR). We developed a parameterization procedure to infer the patient-specific shape of this envelope directly from routine ramp-test data. We then embedded the parameterized envelope within the PSCOPE framework, a hybrid platform that couples a lumped-parameter network to a physical HeartMate 3 flow loop, to reproduce clinical ramp hemodynamics. Percent residuals between simulated outputs and the corresponding clinical measurements verified the implementation of the PV envelope within PSCOPE. ResultsIn three HeartMate 3 recipients, the PSCOPE models reproduced ramp hemodynamics with residuals generally [≤] 20% across pump speeds and measured variables. Cardiac index residuals ranged from 0-18.5%, systemic and pulmonary arterial pressure residuals remained [≤] 18.4%, and pulmonary arterial wedge pressure residuals remained [≤] 20%. The PSCOPE models matched central venous pressure within [≤] 3 mmHg in all cases, although one setting yielded a 33.3% residual due to a low reference pressure. For one patient, the model reproduced ramp hemodynamics at a speed deliberately withheld from PV-envelope parameterization with residuals [≤] 10%, supporting cross-speed generalizability. Patient-specific PV envelopes also revealed clinically meaningful heterogeneity in LV diastolic stiffness, volume threshold for declining systolic function, operating PV points for peak systolic function, and contractile reserve. ConclusionsRamp-integrated parameterization of the monotonic pPVR and unimodal aPVR yields a compact, mechanistic PV envelope that is identifiable from routine clinical data and verifiable within PSCOPE. The resulting indices characterize intrinsic LV function and may enhance longitudinal recovery surveillance and inform LVAD management. Prospective multicenter validation is warranted to confirm the generalizability and clinical utility of this approach.

IntroductionStereological estimates of villous membrane thickness and surface area are widely used to infer the diffusive exchange capacity of the human placenta. A key geometric determinant of exchange capacity can be expressed as an effective diffusive length scale. Here we combine virtual histological sections with computational modelling in realistic villous geometries to assess the accuracy of classical stereological estimates of this diffusive length scale. MethodsTwo terminal villi, reconstructed from three-dimensional imaging, were digitally sectioned to generate random two-dimensional geometries containing fetal capillaries and surrounding villous tissue. For each section, we simulated steady diffusive transport between the fetal capillary and intervillous space boundaries to obtain a physics-based diffusive length scale as a reference case. Using the same geometries, we applied standard line-intercept stereology to measure harmonic-mean barrier thickness and boundary-length densities, from which a stereological estimate of diffusive length scale was derived. ResultsAcross both villi, stereology systematically overestimated the diffusive length scale by approximately 15-25%, depending on villus and section. We identified sources of this discrepancy, including interface curvature and assumptions underpinning the stereological correction factors, using idealised models of villus structure. ConclusionThese findings highlight the need for stereological approaches that account for curvature when interpreting placental structure-function relationships.

Within the medical field, there are multiple opportunities in which 3D printed anatomical models could be utilized such as physician training, surgical planning, education, and R&D testing. Because of this, it is vital to choose materials that most closely mechanically mimic the tissues that would be seen within the simulated model. Stratasys currently has a line of Digital Anatomy (DA) printers that contain predetermined compositions and mixtures called anatomical presets to mimic soft tissue materials such as liver, myocardium, aortic, and epicardium tissue. Different compositions of these printed materials have been previously printed on the J750 Digital Anatomy printer and have undergone mechanical testing. Stratasys is releasing a new printer called J5 Digital Anatomy printer that will also have the capabilities of printing anatomical presets. To compare any differences between the two printer sample types, these mechanical tests were repeated on the J5 DA printer. Mechanical testing included stiffness testing of printed liver samples, compliance testing of printed myocardium samples, and lubricity testing of printed cardiac tissue samples. Stiffness of J5 DA liver and J750 DA liver samples were similar with slight variation seen in more rigid J5 DA samples; however, both printer samples still fell within the stiffness range observed in porcine liver tissue. Compliance testing showed comparable stiffness between J5 DA and J750 DA myocardium samples; however, J5 DA samples tended to be slightly less stiff making them more similar to porcine myocardium stiffness. Thinner J5 DA samples were more variable when compared to J750 DA samples; however, this was minimal variability when compared to that experienced in porcine tissue. Lubricity testing showed comparable coefficients of friction between J5 DA and J750 DA samples with the exception of Mineral oil and Dry lubricants. J5 DA cardiac samples saw smaller coefficients of friction; however, these still fell within the range of aortic and epicardium coefficients of frictions. Because of these results, it can be concluded that the J5 DA printer samples are comparable to J750 DA printer samples and are alternatives to animal tissue benchtop testing depending on the application.

This study describes and validates a novel mechanical testing apparatus capable of generating a viscoelastic response from which the time-dependent behavior of human cerebrovascular tissue can be derived to inform vessel wall failure prediction and therapeutic device design. Testing involved vascular specimen cannulation, pressurization, and recording dynamic changes in vessel diameter using a three-axis laser micrometer. Device validity and versatility were evaluated via two synthetic microvessel specimen experiments: (I) comparison to an Instron stress-relaxation protocol, and (II) vessel segment length parametric analysis. A standard linear solid (SLS) model was chosen to fit the experimental results, from which the model coefficients (E1, E2, and ) and equilibrium modulus (Ge) were computed. Ge comparisons were made using Bland-Altman analysis and Welchs F-test for experiment I and II, respectively. Device feasibility was evaluated through testing human cadaveric cerebrovascular tissue. The SLS model provided accurate experimental data fits, with overall mean R2 value of 0.99 (SD= 2.4E-3). Ge for inflation-creep and Instron stress-relaxation experiments were statistically comparable, with Bland-Altman mean bias of 1.9% (95% CI: -0.9% - 4.6%, p=.18). Holistically, the vessel segment length parametric analysis revealed inconsistent values for Ge across the complete range of testing lengths, where ad hoc family-wise comparison indicated that the 0.5 cm length cohort was the singular outlier (p < .05). Our device successfully recorded a viscoelastic response from human cadaveric middle cerebral artery tissue (n=12). This study demonstrated that our novel device was both versatile and capable of eliciting an accurate viscoelastic response.

The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30-50% of AVFs undergo primary failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies also identified an FCAD geometry with a tab angle, height, and aspect ratio of 30{degrees}, 0.1 diameters, and 1.0 restored time-averaged WSS along the inner venous wall, achieving a physiological level without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle imaging velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall is expected to preserve endothelial function and improve AVF maturation.

ObjectiveTo make steerable needles more effective, researchers have been trying to minimize turning radius, develop mechanics-based models, and simplify control. This paper introduces a novel cable-driven steerable needle that has a 3mm turning radius based on tape spring mechanics, which sets a new minimum turn radius in stiffness-matched tissue models. Methods: We characterize the turn radius and the forces that affect control and performance and create predictive models to estimate required insertion forces and maximum insertion depth. Finally, we demonstrate the performance of a task outside the capabilities of a conventional needle. Results: Minimal force is required to maintain bends, allowing surrounding tissue to fix them in place, and minimal energy is required to propagate bends, allowing the device to navigate easily through various tissue phantoms. The turn radius of the device is independent of surrounding tissue stiffness, making for simple and precise control. We show that all aspects of performance depend on minimizing the tip cutting force. Under ultrasound guidance, we successfully navigate into and then follow a deep blood vessel model at a steep angle of approach. Conclusion: This design allows the system to accurately control the direction of the device while maintaining a smaller turn radius than other steerable needles, providing the potential to broaden access to challenging targets in patients.

Uterine rupture is an intrinsically biomechanical process associated with high maternal and fetal mortality. A previous Cesarean section (C-section) is the main risk factor for uterine rupture in a subsequent pregnancy due to tissue failure at the scar region. Finite element modeling of the uterus and scar tissue presents a promising method to further understand and predict uterine ruptures. Using patient dimensions of an at-term uterus, a C-section scar was modeled with an applied intrauterine pressure to study how scars affect uterine stress. The scar positioning and uterine thickness were varied, and a defect was incorporated into the scar region. The modeled stress distributions confirmed clinical observations as the increased regions of stress due to scar positioning, thinning of the uterine walls, and the presence of a defect are consistent with clinical observations of features that increase the risk of uterine rupture.

The buccal mucosa is a highly interesting site for non-invasive drug delivery due to its relatively permeable epithelium and good accessibility. Recently, device-based systems have enabled the delivery of macromolecular drugs by leveraging mechanical stretching forces on the tissue to assist drug diffusion. Despite the successful exploitation of the buccal route with such systems, the biomechanics of buccal tissue are still poorly characterized and understood due to a lack of adequate characterization methods. Therefore, we propose a combination of physiological tissue modeling with simple suction experiments as a tool for characterizing and understanding the buccal tissue under the impact of negative pressure. Here, we present an initial step towards a multiphasic and poroelastic model specifically designed for the non-keratinized buccal tissue under the impact of negative pressure. A validated finite element model (FEM) for human skin was adapted to represent the histological structure of porcine buccal tissue. We performed suction experiments using the NIMBLE device, specifically developed for measuring skin stiffness, to characterize its mechanical behavior and train the FEM model. The resulting simulation tracks essential physiological parameters and allows the prediction of measurable changes in the tissue, such as the thinning of the epithelium and single-cell stretching. The FEM simulation was validated through histochemically stained tissue sections at the NIMBLE application site. A good correlation was demonstrated between predicted and experimentally observed changes. This work serves as a first step towards a computational representation of buccal tissue under the impact of negative pressure.

Poor socket fit is the leading cause of prosthetic limb discomfort. However, currently clinicians have limited objective data to support and improve socket design. Prosthesis fit could be predicted by finite element analysis to help improve the fit, but this requires internal and external anatomy models. While external 3D surface scans are often collected in routine clinical computer aided design practice, detailed imaging of internal anatomy (e.g. MRI or CT) is not. This paper presents a prototype Statistical Shape Model (SSM) describing the transtibial amputated residual limb, generated using a sparse dataset of 10 MRI scans. To describe the maximal shape variance, training scans are size-normalised to their estimated intact tibia length. A mean limb is calculated, and Principal Component Analysis used to extract the principal modes of shape variation. In an illustrative use case, the model is interrogated to predict internal bone shapes given a skin surface shape. The model attributes [~]82% of shape variance to amputation height and [~]7.5% to soft tissue profile. Leave-One-Out cross-validation allows mean shape reconstruction with 0.5-3.1mm root-mean-squared-error (RMSE) surface deviation (median 1.0mm), and left-out-shape reconstruction with 4.8-8.9mm RMSE (median 6.1mm). Linear regression between mode scores from skin- only- and full-model SSMs allowed prediction of bone shapes from the skin surface with 4.9-12.6mm RMSE (median 6.5mm). The model showed the feasibility of predicting bone shapes from skin surface scans, which will enable more representative prosthetic biomechanics research, and address a major barrier to implementing simulation within clinical practice. Impact StatementThe presented Statistical Shape Model answers calls from the prosthetics community for residual limb shape descriptions to support prosthesis structural testing that is representative of a broader population. The SSM allows definition of worst-case residual limb sizes and shapes, towards testing standards. Further, the lack of internal anatomic imaging is one of the main barriers to implementing predictive simulations for prosthetic socket interface fitting at the point-of-care. Reinforced with additional data, this model may enable generation of estimated finite element analysis models for predictive prosthesis fitting, using 3D surface scan data already collected in routine clinical care. This would enable prosthetists to assess their design choices and predict a sockets fit before fabrication, important improvements to a time-consuming process which comes at high cost to healthcare providers. Finally, few researchers have access to residual limb anatomy imaging data, and there is a cost, inconvenience, and risk associated with putting the small community of eligible participants through CT or MRI scanning. The presented method allows sharing of representative synthetic residual limb shape data whilst protecting the data contributors privacy, adhering to GDPR. This resource has been made available at https://github.com/abel-research/openlimb, open access, providing researchers with limb shape data for biomechanical analysis.

ObjectivesThrombotic deposition is a major consideration in the development of implantable cardiovascular devices. Recently, it has been experimentally demonstrated that localized changes in the blood shear rate -i.e. shear gradients-play a critical role in thrombogenesis. The goal of the present work is to develop a predictive computational model of platelet plug formation that can be used to assess the thrombotic burden of cardiovascular devices, introducing for the first time the role of shear gradients. We have developed a comprehensive model of platelet-mediated thrombogenesis which includes platelet transport in the blood flow, platelet activation and aggregation induced by both biochemical and mechanical factors, kinetics and mechanics of platelet adhesion, and changes in the local fluid dynamics due to the thrombus growth. MethodsA 2D computational model was developed using the multi-physics finite element solver COMSOL 5.6. The model can be described by a coupled set of convection-diffusion-reaction equations. Platelet adhesion at the surface was modeled via flux boundary conditions. Using a moving mesh for the surface, thrombus growth and consequent alterations in blood flow were modeled. In the case of a stenosis, the notions of shear stress induced platelet activation in the contraction zone and shear gradients induced platelet deposition in the expansion zone downstream of the stenosis were studied. ResultsThe model provides the spatial and temporal evolution of platelet plug in the flow field. The computed platelet plug size evolution was validated against literature data. The results confirm the importance of considering both mechanical and chemical aggregation of platelets. ConclusionsThe developed model represents a potentially useful tool for the optimization of the design of the cardiovascular device flow path.

Stent-artery interactions are influenced by the mechanical properties of self-expanding Nitinol stents, but data on these characteristics remain limited. Eleven stents (Absolute Pro, S.M.A.R.T. Control, Misago, Zilver, Complete SE, EverFlex, Innova, Pulsar-18, LifeStent, S.M.A.R.T. Flex, and Supera) used to treat peripheral arterial disease (PAD) were subjected to axial tension, compression, three-point bending, and torsion tests, and the data on reaction forces and moments were compared with finite element simulations of the same experiments. Inverse computational analysis was used to determine austenite and martensite elasticity, transformation stretch, stresses at the start and end of transformation loading, and the start of transformation stress in compression. Uniaxial tensile tests were done on isolated struts from Absolute Pro and Zilver stents to verify the results of the inverse analysis. Our study demonstrate that Nitinol material properties are significantly different across devices. Austenite elasticity ranged 7.5-85 GPa, martensite elasticity 10-47.8 GPa, transformation stretch 1.03-1.08, the start of transformation loading stress 386-465 MPa, the end of transformation loading stress 411-535 MPa, and the start of transformation stress in compression 150-900 MPa. Nitinol of S.M.A.R.T. Control and S.M.A.R.T. Flex devices had the softest response, while Pulsar-18 had the hardest. The presented Nitinol mechanical properties of commonly used PAD stents can improve the fidelity of computational models investigating stent-artery interactions and may help improve clinical outcomes of endovascular PAD repairs through better device design.

Most studies investigating arterial stiffening use animal rather than human arteries. This is because human tissue becomes available in small amounts and at irregular times, which complicates planning of experimental work. Suitable tissue preservation methods for delayed biomechanical testing prevents the need for testing fresh tissue and alleviates some of the logistical challenges of human ex vivo studies. Therefore, the present study aimed to investigate whether the existing method of flash freezing and subsequent cryostorage provides is suitable for delaying the characterization of arterial biomechanics. Fresh and flash frozen abdominal aortas (n=16 and 14, respectively) were quasi- statically and dynamically tested using a biaxial testing set-up with dynamic pressurization capabilities. The acquired biomechanical data was modeled using a constituent-based quasi-linear viscoelastic modeling framework, deriving directional stiffness parameters, individual constituent biomechanical contributions, and viscoelastic stiffening under dynamic pressurization conditions. Flash freezing reduced arterial wall thickness, increased circumferential stiffness, as well as reduced viscoelastic stiffening at higher pressures. These findings reflected those in the modeled contribution of collagen to arterial biomechanics, showing increased collagen load bearing at higher pressures. However, despite the above mentioned detectable changes, flash freezing did not alter the mechanical relation between elastin and collagen, maintaining a non-linear response to pressurization and stretch. Flash freezing may thus be suitable for studies requiring delayed characterization of passive arterial biomechanics, assuming care is taken to ascert that the impact of flash freezing on study groups can be approached as a systematic error.

IntroductionDiabetic foot ulcers are open wounds with impaired wound closure at the bottom of the foot. Although diabetic plantar skin is stiffer, which should enhance fibroblast mechanotransduction, fibroblasts still fail to migrate effectively. This suggests impaired wound closure is driven by another factor; hyperglycemia ([&ge;]11.1 mM glucose), which alters fibroblast mechanotransduction. PurposeTo mimic diabetic foot ulcers by developing a 2D circular in vitro wound closure model system to investigate fibroblast mechanoresponse under diabetic plantar skin stiffness and hyperglycemia. MethodsPolydimethylsiloxane was used as substrate, fabricated at 57 kPa and 90 kPa for normal and diabetic plantar skin stiffnesses, respectively. Cell culture media contained a 5.5 mM glucose concentration simulating normal blood glucose or an altered 11.1 mM glucose concentration simulating hyperglycemia. ResultsTime-lapse fluorescent imaging of wound assays reveals a restrictive effect of higher stiffness on migrating fibroblasts under normal glucose conditions, and a biphasic response to hyperglycemic conditions. Fibroblasts migrating on softer substrates mimicking normal plantar skin stiffness and under hyperglycemia have decreased velocity as predicted. Whereas cells migrating on stiffer substrates mimicking diabetic plantar skin stiffness and under hyperglycemia demonstrate increased cell velocity, overcoming the higher stiffnesss restrictive effect. Despite faster cell velocities on higher stiffness, wounds under normal glucose conditions still close faster than those under hyperglycemic conditions. ConclusionThis research establishes a wound closure model demonstrating significantly slower wound closure in diabetic plantar skin with higher stiffness and hyperglycemic glucose levels compared to normal plantar skin with softer stiffness and normal glucose levels.

PurposeTo investigate the interplay between biomechanics, fluid dynamics, and solute transport in Diabetic Macular Oedema (DMO) using a mechanics-based computational model, aiming to elucidate mechanisms behind variable treatment outcomes. MethodsWe developed a multiphysics model of the retina within a porous media framework. The model integrates OCT-derived geometry, vascular leakage, retinal biomechanics (including Muller cell fibre architecture), retinal pigment epithelium (RPE) function, and anti-VEGF transport. We simulated oedema development and therapeutic response by varying these parameters systematically. ResultsModel results showed that active RPE pumping is essential for maintaining retinal dehydration. Our simulations revealed a critical trade-off related to Muller cell architecture: the physiological z-shaped orientation protects against oedema but impedes anti-VEGF drug delivery to leaky vessels. In contrast, a pathological, vertical Muller cell alignment increases oedema susceptibility but allows for a faster therapeutic response due to improved drug diffusion. ConclusionsMuller cell orientation presents a trade-off between biomechanical protection and therapeutic efficacy, offering a novel mechanistic explanation for the variable patient responses to anti-VEGF therapy observed clinically. This in-silico framework is a powerful tool for dissecting DMO pathophysiology and has the potential to guide the development of personalised treatment strategies.

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen and carbon dioxide to and from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow range of parameters that determine gas exchange efficiency and blood flow resistance, such as fiber packing density, path length, and frontal area. However, these parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3-D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro-rods (380 micron diameter) arranged with varying packing densities (40, 50, and 60%) and path lengths (2 and 4 cm). Blood was pumped through the device corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of fiber bundle enhances deposition upstream, and consequently (3) greater path length provides more clot-free fiber surface area for gas exchange than a shorter path length. These results can be used to create less thrombogenic, more efficient artificial lung designs. Translational Impact SentenceFiber bundle parameters, such as decreased packing density, increased blood flow velocity, and a longer path length, can be used to design a less thrombogenic, more efficient artificial lung to extend functionality.

The shoulder joint complex is prone to musculoskeletal issues, such as rotator cuff-related pain, which affect two-thirds of adults and often result in suboptimal treatment outcomes. Current musculoskeletal models used to understand shoulder biomechanics are limited by challenges in personalization, inaccuracies in predicting joint and muscle loads, and an inability to simulate anatomically accurate motions. To address these deficiencies, we developed a novel, personalized modeling framework capable of calibrating subject-specific joint centers and functional axes for the shoulder complex. Leveraging in vivo biplane fluoroscopy data and the recent Joint Model Personalization Tool from the Neuromusculoskeletal Modeling Pipeline, we optimized joint parameters and body scale factors for shoulder models with varying degrees of freedom (DOFs). We initially created and tested open-chain scapula-only models (3DOF, 4DOF, and 5DOF) and found that increasing DOFs improved accuracy, with the 5 DOF model yielding the lowest marker distance errors (average = 0.8 mm, maximum = 5.2 mm) as compared to biplane fluorscopy data of the scapula across eight movement trials. We subsequently created closed-chain shoulder models incorporating scapula, clavicle, and humerus bodies. We found closed-chain shoulder models with 5 DOFs for the scapula achieved the highest accuracy (average = 0.9 mm, maximum = 5.7 mm) and showed consistent performance across subjects (n=3) in leave-one-out cross-validation tests (average marker distance errors = 1.0-1.4 mm). This framework minimizes errors in joint kinematics and provides a foundation for future models incorporating personalized musculature and advanced simulations, enhancing its potential clinical utility for rehabilitation and surgical planning.

BackgroundPeripheral intravenous catheters (PIVCs) are the most commonly used invasive medical device, yet despite best efforts by end-users, PIVCs experience unacceptably high early failure rates. We aimed to design a new PIVC that reduces the early failure rate of in-dwelling PIVCs and we conducted preliminary tests to assess its efficacy and safety in a large animal model of intravenous access. MethodsWe used computer-aided design and simulation to create a PIVC with a ramped tip geometry, which directs the infused fluid away from the vein wall; we called the design the FloRamp. We created FloRamp prototypes (test device) and tested them against a market-leading device (BD Insyte; control device) in a highly-controlled setting with five insertion sites per device in four pigs. We measured resistance to infusion and visual infusion phlebitis (VIP) every six hours and terminated the experiment at 48 hours. Veins were harvested for histology and seven pathological markers were assessed. ResultsComputer simulations showed that the optimum FloRamp tip reduced maximum endothelial shear stress by 60%, from 12.7Pa to 5.1Pa, compared to a typical PIVC tip, and improved the infusion dynamics of saline in the blood stream. In the animal study, we found that 2/5 of the control devices were occluded after 24 hours, whereas all test devices remained patent and functional. The FloRamp created less resistance to infusion (0.73{+/-}0.81 vs 0.47{+/-}0.50, p=0.06) and lower VIP scores (0.60{+/-}0.93 vs 0.31{+/-}0.70, p=0.09) that the control device, although neither findings were significantly different. Histopathology revealed that 5/7 of the assessed markers were lower in veins with the FloRamp. ConclusionsAs PIVCs are used in almost every hospitalized patient, there is an urgent need to reduce failure rates. Herein we report preliminary assessment of a novel PIVC design, which could be advantageous in clinical settings through decreased device occlusion.

SignificanceMastectomy skin flap necrosis remains a major complication in implant-based breast reconstruction due to inadequate tissue blood flow. Existing diagnostic technologies are limited by shallow depth sensitivity, dye-related risks, contact requirements, and an inability to continuously assess blood flow. AimThis study aimed to translate a noncontact, dye-free, depth-sensitive speckle contrast diffuse correlation tomography (scDCT) technique to a clinically relevant porcine skin flap model for assessing flap blood flow and viability. ApproachThe scDCT system was optimized to image blood flow over seven days in four porcine skin flaps including Sham (SH), Implant (IM), Half Necrosis (HN), and Full Necrosis (FN). Measurements were compared with indocyanine green angiography (ICG-A) as a reference standard. ResultsscDCT enabled longitudinal monitoring of flap blood flow, revealing significant flow differences among flap types and over time. FN flaps consistently exhibited the most severe flow impairment, while other flap types showed partial or complete recovery over time, distinguishing nonviable from viable tissue. scDCT measurements demonstrated moderate to strong correlations with ICG-A across time points. ConclusionsThe findings support scDCT as a promising perioperative imaging modality for improving flap necrosis risk stratification and surgical decision-making, with future work focused on large-scale validation and clinical translation.

Blood vessels anastomosis is one of the most challenging and delicate tasks to learn in many surgical specialties, especially for vascular and abdominal surgeons. Such a critical skill implies a learning curve that goes beyond technical execution. The surgeon needs to gain proficiency in adapting gestures and the amount of force expressed according to the type of tissue he/she is dealing with. In this context, surgical simulation is gaining a pivotal role in the training of surgeons, but currently available simulators can provide only standard or simplified anatomies, without the chance of presenting specific pathological conditions and rare cases. 3D printing technology, allowing the manufacturing of extremely complex geometries, find a perfect application in the production of realistic replica of patient-specific anatomies. According to available technologies and materials, morphological aspects can be easily handled, while the reproduction of tissues mechanical properties still poses major problems, especially when dealing with soft tissues. The present work focuses on blood vessels, with the aim of identifying - by means of both qualitative and quantitative tests - materials combinations able to best mimic the behavior of the biological tissue during anastomoses, by means of J750 Digital Anatomy technology and commercial photopolymers from Stratasys. Puncture tests and stitch traction tests are used to quantify the performance of the various formulations. Surgical simulations involving anastomoses are performed on selected clinical cases by surgeons to validate the results. A total of 37 experimental materials were tested and 2 formulations were identified as the most promising solutions to be used for anastomoses simulation. Clinical applicative tests, specifically selected to challenge the new materials, raised additional issues on the performance of the materials to be considered for future developments.