Physiological Flow Research Articles

In Vitro Models of Biological Barriers for Nanomedical Research.

Nanoconstructs developed for biomedical purposes must overcome diverse biological barriers before reaching the target where playing their therapeutic or diagnostic function. In vivo models are very complex and unsuitable to distinguish the roles plaid by the multiple biological barriers on nanoparticle biodistribution and effect; in addition, they are costly, time-consuming and subject to strict ethical regulation. For these reasons, simplified in vitro models are preferred, at least for the earlier phases of the nanoconstruct development. Many in vitro models have therefore been set up. Each model has its own pros and cons: conventional 2D cell cultures are simple and cost-effective, but the information remains limited to single cells; cell monolayers allow the formation of cell–cell junctions and the assessment of nanoparticle translocation across structured barriers but they lack three-dimensionality; 3D cell culture systems are more appropriate to test in vitro nanoparticle biodistribution but they are static; finally, bioreactors and microfluidic devices can mimicking the physiological flow occurring in vivo thus providing in vitro biological barrier models suitable to reliably assess nanoparticles relocation. In this evolving context, the present review provides an overview of the most representative and performing in vitro models of biological barriers set up for nanomedical research.

Outcomes of bidirectional Glenn surgery done without prior cardiac catheterization

BackgroundCardiac catheterization is usually done routinely in patients with univentricular hearts before palliative Bidirectional Glenn (BDG) surgery. The objective of this study was to compare the outcomes of patients with physiological univentricular hearts and restrictive pulmonary flow that did not undergo routine cardiac catheterization before BDG with the patients that did have cardiac catheterization done. We retrospectively reviewed the data of all patients with single ventricle physiology and restrictive pulmonary blood flow who underwent BDG surgery from January 2016 till December 2020. Patients were divided into two groups: the catheterization and the non-catheterization groups.ResultsOut of 93 patients, 25 (27%) underwent BDG surgery without prior cardiac catheterization. The median age of patients was ten months, interquartile range (IQR) was 5–18 months. Tricuspid atresia represented 36% of the non-catheterization group, while unbalanced atrioventricular septal defect and hypoplastic left heart syndrome represented 19% and 17.6% of the catheterization group. No patients in the catheterization group were excluded from further BDG surgery based on the catheterization data. Moreover, no significant differences were found between the patients' groups regarding the length of hospital stay, length of intensive care unit stay, postoperative oxygen saturation, or survival (P = 0.266, P = 0.763, P = 0.543, P = 0456).ConclusionsAlthough pre-BDG cardiac catheterization is the routine and standard practice, in certain situations, some patients with single ventricle physiology and restrictive pulmonary blood flow may go directly to BDG without cardiac catheterization if noninvasive imaging is satisfactory on a case-by-case basis and according to center experience. Pre-BDG catheterization could be reserved for patients with limited echocardiographic studies, high-risk patients, or those indicated for catheter intervention before BDG surgery.

Contrast-enhanced ultrasound tracking of helical propellers with acoustic phase analysis and comparison with color Doppler.

Medical microrobots (MRs) hold the potential to radically transform several interventional procedures. However, to guarantee therapy success when operating in hard-to-reach body districts, a precise and robust imaging strategy is required for monitoring and controlling MRs in real-time. Ultrasound (US) may represent a powerful technology, but MRs' visibility with US needs to be improved, especially when targeting echogenic tissues. In this context, motions of MRs have been exploited to enhance their contrast, e.g., by Doppler imaging. To exploit a more selective contrast-enhancement mechanism, in this study, we analyze in detail the characteristic motions of one of the most widely adopted MR concepts, i.e., the helical propeller, with a particular focus on its interactions with the backscattered US waves. We combine a kinematic analysis of the propeller 3D motion with an US acoustic phase analysis (APA) performed on the raw radio frequency US data in order to improve imaging and tracking in bio-mimicking environments. We validated our US-APA approach in diverse scenarios, aimed at simulating realistic in vivo conditions, and compared the results to those obtained with standard US Doppler. Overall, our technique provided a precise and stable feedback to visualize and track helical propellers in echogenic tissues (chicken breast), tissue-mimicking phantoms with bifurcated lumina, and in the presence of different motion disturbances (e.g., physiological flows and tissue motions), where standard Doppler showed poor performance. Furthermore, the proposed US-APA technique allowed for real-time estimation of MR velocity, where standard Doppler failed.

Biofabrication of Sodium Alginate Hydrogel Scaffolds for Heart Valve Tissue Engineering.

Every year, thousands of aortic valve replacements must take place due to valve diseases. Tissue-engineered heart valves represent promising valve substitutes with remodeling, regeneration, and growth capabilities. However, the accurate reproduction of the complex three-dimensional (3D) anatomy of the aortic valve remains a challenge for current biofabrication methods. We present a novel technique for rapid fabrication of native-like tricuspid aortic valve scaffolds made of an alginate-based hydrogel. Using this technique, a sodium alginate hydrogel formulation is injected into a mold produced using a custom-made sugar glass 3D printer. The mold is then dissolved using a custom-made dissolving module, revealing the aortic valve scaffold. To assess the reproducibility of the technique, three scaffolds were thoroughly compared. CT (computed tomography) scans showed that the scaffolds respect the complex native geometry with minimal variations. The scaffolds were then tested in a cardiac bioreactor specially designed to reproduce physiological flow and pressure (aortic and ventricular) conditions. The flow and pressure profiles were similar to the physiological ones for the three valve scaffolds, with small variabilities. These early results establish the functional repeatability of this new biofabrication method and suggest its application for rapid fabrication of ready-to-use cell-seeded sodium alginate scaffolds for heart valve tissue engineering.

On non-Kolmogorov turbulence in blood flow and its possible role in mechanobiological stimulation

The study of turbulence in physiologic blood flow is important due to its strong relevance to endothelial mechanobiology and vascular disease. Recently, Saqr et al. (Sci Rep 10, 15,492, 2020) discovered non-Kolmogorov turbulence in physiologic blood flow in vivo, traced its origins to the Navier–Stokes equation and demonstrated some of its properties using chaos and hydrodynamic-stability theories. The present work extends these findings and investigates some inherent characteristics of non-Kolmogorov turbulence in monoharmonic and multiharmonic pulsatile flow under ideal physiologic conditions. The purpose of this work is to propose a conjecture for the origins for picoNewton forces that are known to regulate endothelial cells’ functions. The new conjecture relates these forces to physiologic momentum-viscous interactions in the near-wall region of the flow. Here, we used high-resolution large eddy simulation (HRLES) to study pulsatile incompressible flow in a straight pipe of L/D=20. The simulations presented Newtonian and Carreau–Yasuda fluid flows, at R{e}_{m}approx 250, each represented by one, two and three boundary harmonics. Comparison was established based on maintaining constant time-averaged mass flow rate in all simulations. First, we report the effect of primary harmonics on the global power budget using primitive variables in phase space. Second, we describe the non-Kolmogorov turbulence in frequency domain. Third, we investigate the near-wall coherent structures in time and space domains. Finally, we propose a new conjecture for the role of turbulence in endothelial cells’ mechanobiology. The proposed conjecture correlates near-wall turbulence to a force field of picoNewton scale, suggesting possible relevance to endothelial cells mechanobiology.

A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model.

The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous “extravasation” process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect (tumor cell apoptosis). Since NK cells infiltration and phenotype is correlated with prognosis and response to immunotherapy, their phenotype is also investigated: most importantly, a clear decrease in CD16-positive NK cells within the migrated and infiltrated population is observed. The proposed immune-tumor OOC-based model represents a promising approach for faithfully recapitulating the human pathology and efficiently employing the immunotherapies testing, eventually in a personalized perspective. An immune-organ on chip to recapitulate the tumor-mediated infiltration of circulating immune cells within 3D tumor model.

Baseline Hemodynamics Including Aortic and Pulmonary Blood Flow in a Chronic Bovine Model

The use of large animal models in the preclinical setting has expanded and become increasingly valuable for evaluating the safety and efficacy of new therapies and devices. Here, we report normal hemodynamic values, including aortic and pulmonary blood flow, in a bovine model at rest and during exercise after a control procedure. We performed a left lateral thoracotomy and implanted fluid-filled pressure lines (aortic pressure, right atrial pressure, left atrial pressure, pulmonary artery pressure) and left (systemic) and right (pulmonary) flow probe lines. Throughout the postoperative period, the calf’s physiologic pressures, vital signs, aortic and pulmonary blood flow, and pulmonary and systemic vascular resistance were recorded hourly at rest and during treadmill exercise evaluations. When pressures and flow rates at baseline and during treadmill trials were compared, we observed a physiologic response to exercise similar to that seen in humans, with a sympathetic discharge that increased systolic blood pressure. However, the rise in mean arterial pressure was much lower due to an overall decrease in vascular resistance, which increased blood flow. This study provides investigators, device engineers, and manufacturers with normal bovine cardiovascular physiology data that can be used for technical consideration during device development for preclinical trials.

Physiologic Data-Driven Iterative Learning Control for Left Ventricular Assist Devices.

Continuous flow ventricular assist devices (cfVADs) constitute a viable and increasingly used therapy for end-stage heart failure patients. However, they are still operating at a fixed-speed mode that precludes physiological cfVAD response and it is often related to adverse events of cfVAD therapy. To ameliorate this, various physiological controllers have been proposed, however, the majority of these controllers do not account for the lack of pulsatility in the cfVAD operation, which is supposed to be beneficial for the physiological function of the cardiovascular system. In this study, we present a physiological data-driven iterative learning controller (PDD-ILC) that accurately tracks predefined pump flow trajectories, aiming to achieve physiological, pulsatile, and treatment-driven response of cfVADs. The controller has been extensively tested in an in-silico environment under various physiological conditions, and compared with a physiologic pump flow proportional-integral-derivative controller (PF-PIDC) developed in this study as well as the constant speed (CS) control that is the current state of the art in clinical practice. Additionally, two treatment objectives were investigated to achieve pulsatility maximization and left ventricular stroke work (LVSW) minimization by implementing copulsation and counterpulsation pump modes, respectively. Under all experimental conditions, the PDD-ILC as well as the PF-PIDC demonstrated highly accurate tracking of the reference pump flow trajectories, outperforming existing model-based iterative learning control approaches. Additionally, the developed controllers achieved the predefined treatment objectives and resulted in improved hemodynamics and preload sensitivities compared to the CS support.

The spectrin cytoskeleton integrates endothelial mechanoresponses

Physiological blood flow induces the secretion of vasoactive compounds, notably nitric oxide, and promotes endothelial cell elongation and reorientation parallel to the direction of applied shear. How shear is sensed and relayed to intracellular effectors is incompletely understood. Here, we demonstrate that an apical spectrin network is essential to convey the force imposed by shear to endothelial mechanosensors. By anchoring CD44, spectrins modulate the cell surface density of hyaluronan and sense and translate shear into changes in plasma membrane tension. Spectrins also regulate the stability of apical caveolae, where the mechanosensitive PIEZO1 channels are thought to reside. Accordingly, shear-induced PIEZO1 activation and the associated calcium influx were absent in spectrin-deficient cells. As a result, cell realignment and flow-induced endothelial nitric oxide synthase stimulation were similarly dependent on spectrin. We conclude that the apical spectrin network is not only required for shear sensing but also transmits and distributes the resulting tensile forces to mechanosensors that elicit protective and vasoactive responses.

Thermal transport of two-phase physiological flow of non-Newtonian fluid through an inclined channel with flexible walls

Magnetohydrodynamics (MHD) of a non-Newtonian fluid with heat transfer through a porous medium is examined here. Jeffrey fluid is taken as the base liquid with suspends with homogenous and spherical solid particles. A peristaltic wave travels along the flexible walls of the channel. Flow is caused by the expansion and contraction of the walls along with the gravitational force. Lubrication effects are considered on both flexible walls of the channel. An exact solution is obtained for the two-phase flow of Jeffrey fluid with heat transfer. A comprehensive parametric study is carried out to analyze the role of pertinent parameters and it is inferred that a porous medium supports the flow Darcy number while strong magnetic fields hamper the flow. More thermal energy is contributed due to radiation causing a reduction in the velocity of the fluid whereas the temperature profile declines in response to varying the permeability of the porous medium. Finally, the comparative analysis reveals that Jeffrey multiphase suspension is more prominent than Newtonian multiphase fluid.

Improved Functional Assessment of Ischemic Severity Using 3D Printed Models.

ObjectiveTo develop a novel in vitro method for evaluating coronary artery ischemia using a combination of non-invasive coronary CT angiograms (CCTA) and 3D printing (FFR3D).MethodsTwenty eight patients with varying degrees of coronary artery disease who underwent non-invasive CCTA scans and invasive fractional flow reserve (FFR) of their epicardial coronary arteries were included in this study. Coronary arteries were segmented and reconstructed from CCTA scans using Mimics (Materialize). The segmented models were then 3D printed using a Carbon M1 3D printer with urethane methacrylate (UMA) family of rigid resins. Physiological coronary circulation was modeled in vitro as flow-dependent stenosis resistance in series with variable downstream resistance. A range of physiological flow rates (Q) were applied using a peristaltic steady flow pump and titrated with a flow sensor. The pressure drop (ΔP) and the pressure ratio (Pd/Pa) were assessed for patient-specific aortic pressure (Pa) and differing flow rates (Q) to evaluate FFR3D using the 3D printed model.ResultsThere was a good positive correlation (r = 0.87, p < 0.0001) between FFR3D and invasive FFR. Bland-Altman analysis revealed a good concordance between the FFR3D and invasive FFR values with a mean bias of 0.02 (limits of agreement: −0.14 to 0.18; p = 0.2).Conclusions3D printed patient-specific models can be used in a non-invasive in vitro environment to quantify coronary artery ischemia with good correlation and concordance to that of invasive FFR.

Dissection Techniques and Histological Sampling of the Heart in Large Animal Models for Cardiovascular Diseases

The standard gross examination and sampling are key elements in the reproducibility and success of experimental studies of cardiovascular diseases carried out in large animals. Considering the complex anatomy of the heart, interspecies differences, and the types of compensatory and pathological reactions, consistent protocols are challenging to implement. The utilization of multiple dissection protocols is usually adapted to suit the prosector's experience, and personal preference continues to be a source of experimental and interobserver variability. Here, the aim is to present the main anatomical features and landmarks, dissection protocols, and histological sampling standards of the heart in some commonly used species (including dogs, pigs, ruminants, and cats) as models of cardiovascular diseases. Two standard gross examination protocols are presented here. First, the inflow-outflow method, which follows the physiological blood flow direction through the heart and large vessels (frequently used in dogs, ruminants, and pigs), and second, the four-chamber dissection technique (exemplified in cats). Both techniques can be adapted to any species in certain experimental circumstances. The sampling protocols include all the areas of interest (sinoatrial node, ventricles, interventricular septum, atria, valves, and aorta), and if properly carried out, improve both the reproducibility and reliability of experimental studies.

Effects of Gas Embolism on Pulsatile Flow Characteristics Within a Human Carotid Artery.

Atherosclerosis in carotid arteries depends mostly on hemodynamic parameters, and any disturbances in pulsatile flows may alter the hemodynamic parameters extensively. Gas emboli are one such source that can hinder and disturb standard blood flow patterns and potentially lead to occlusions and ischemia. To understand how gas embolism affects carotid artery hemodynamics, numerical simulation of coupled Newtonian two-phase laminar flow with interface tracking are performed in an anatomical image-based geometry with flow conditions closely approximating physiological flows. Bubble behavior and Pulsatile flow field changes are quantified. Significant deviation from flow without gas embolism is observed leading to nonstandard flow distributions. Results show that gas embolism promotes complex spatio-temporal variations in the carotid artery hemodynamics leading to higher time averaged shear stress values and greater regions of high oscillatory shear index, implying higher probability of atherosclerosis incidence. Depending on contact angle, gas emboli were found to be lodged in carotid sinus or exiting the carotid artery, which can potentially cause abnormalities in blood pressures, heart rates, and ischemia in downstream vasculature, respectively.

Comparison Between Franz Diffusion Cell and a novel Micro-physiological System for In Vitro Penetration Assay Using Different Skin Models.

In vitro diffusive models are an important tool to screen the penetration ability of active ingredients in various formulations. A reliable assessment of skin penetration enhancing properties, mechanism of action of carrier systems, and an estimation of a bioavailability are essential for transdermal delivery. Given the importance of testing the penetration kinetics of different compounds across the skin barrier, several in vitro models have been developedThe aim of this study was to compare the Franz Diffusion Cell (FDC) with a novel fluid-dynamic platform (MIVO) by evaluating penetration ability of caffeine, a widely used reference substance, and LIP1, a testing molecule having the same molecular weight but a different lipophilicity in the two diffusion chamber systems. A 0.7% caffeine or LIP1 formulation in either water or propylene glycol (PG) containing oleic acid (OA) was topically applied on the Strat-M® membrane or pig ear skin, according to the infinite-dose experimental condition (780 ul/cm2). The profile of the penetration kinetics was determined by quantify the amount of molecule absorbed at different time-points (1, 2, 4, 6, 8 hours), by means of HPLC analysis. Both diffusive systems show a similar trend for caffeine and LIP1 penetration kinetics. The Strat-M® skin model shows a lower barrier function than the pig skin biopsies, whereby the PGOA vehicle exhibits a higher penetration, enhancing the effect for both diffusive chambers and skin surrogates. Most interestingly, MIVO diffusive system better predicts the lipophilic molecules (i.e. LIP1) permeation through highly physiological fluid flows resembled below the skin models.

Comparative Assessment of Isolated Liver Chemoperfusion Techniques

Background. Metastatic liver injury is a distinct oncological problem, irrespective of primary malignancy. Resection surgery is not always feasible in such patients. Isolated liver chemoperfusion is a promising treatment option in multiple small-focal metastatic organic lesions. This technique is technically complex, which limits its broader evaluation and adoption in clinical practice. The diversity of isolated liver chemoperfusion techniques does not allow an adequate assessment of world experience and requires further research. The important considerations with introducing isolated liver chemoperfusion are: an optimal surgical technique, liver isolation control method, as well as physiological arterial and portal blood flow maintenance.Materials and methods. A total of 21 patients were surveyed over June 2020 — December 2021. The patients were divided into 3 prospective cohorts: A) arteriocaval chemoperfusion, midline laparotomy access, technical-guided liver isolation, B) arteriocaval chemoperfusion, “in J laparotomy” access, ICG-guided liver isolation, C) arterio-porto-caval chemoperfusion, “in J laparotomy” access, ICG-guided liver isolation. A procedure’s tolerance was assessed with: the duration of surgery, postoperative ICU bed-days, total postoperative bed-days, hepatic cytolysis rates, chemotherapy side-effects severity.Results and discussion. The duration of surgery shortened with “in J laparotomy”. Haemotoxicity did not differ between cohorts A and B, albeit appearing significantly lower in cohort C. The cytolytic syndrome duration statistically significantly reduced in C vs. A and B cohorts.Conclusion. All the isolated liver chemoperfusion techniques employed are patient-safe. In ICG-guided liver isolation, the agent leakage into systemic blood flow is less likely, indicating a lower haemotoxicity. Arterioportal isolated chemoperfusion is more physiological compared to other techniques, thus facilitating lower hepatotoxicity. The use of “in J laparotomy” significantly reduces liver mobilisation and vascular cannulation times.

Abstract No. 584 Recanalization of chronically occluded portal and mesenteric veins: a non-transplant pediatric cohort

Extrahepatic portal vein obstruction is the most frequent cause of portal hypertension in children. Patients may not be amenable to meso-Rex bypass and alternative surgical bypasses do not restore physiologic portal flow to the liver, a critical component of somatic growth in pediatric patients. Superior mesenteric and splenic vein occlusions, while far less common, are also problematic with regards to GI bleeding. The current literature is lacking in non-transplant patients with portal and other visceral occlusion.

Galectin-9 supports primary T cell transendothelial migration in a glycan and integrin dependent manner

Adaptive immunity relies on the efficient recruitment of T cells from the blood into peripheral tissues. However, the current understanding of factor(s) coordinating these events is incomplete. Previous studies on galectin-9 (Gal-9), have proposed a functionally significant role for this lectin in mediating leukocyte adhesion and transmigration. However, very little is known about its function in T cell migration. Here, we have investigated the role of the Gal-9 on the migration behaviour of both human primary CD4+ and CD8+ T cells. Our data indicate that Gal-9 supports both CD4+ and CD8+ T cell adhesion and transmigration in a glycan dependent manner, inducing L-selectin shedding and upregulation of LFA-1 and CXCR4 expression. Additionally, when immobilized, Gal-9 promoted capture and firm adhesion of T cells under flow, in a glycan and integrin-dependent manner. Using an in vivo model, dorsal air pouch, we found that Gal-9 deficient mice display impaired leukocyte trafficking, with a reduction in pro-inflammatory cytokines/chemokines generated locally. Furthermore, we also demonstrate that Gal-9 inhibits the chemotactic function of CXCL12 through direct binding. In conclusion, our study characterises, for the first time, the capture, adhesion, and migration behaviour of CD4+ and CD8+ T cells to immobilised /endothelial presented Gal-9, under static and physiological flow conditions. We also demonstrate the differential binding characteristics of Gal-9 to T cell subtypes, which could be of potential therapeutic significance, particularly in the treatment of inflammatory-based diseases, given Gal-9 ability to promote apoptosis in pathogenic T cell subsets.

Mathematical computations for the physiological flow of Casson fluid in a vertical elliptic duct with ciliated heated wavy walls

This mathematical investigation discloses the peristaltic flow of non-Newtonian fluid in a vertical duct with an elliptic cross-section and ciliated walls. The Casson fluid’s non-Newtonian model is utilized for an elliptic duct with heated ciliated walls. The physical aspects of cilia-driven metachronal wave combined with sinusoidal wavy wall movement are highlighted. A set of dimensionless partial differential equations with relevant boundary conditions is obtained after simplifying the dimensional form of governing equations using appropriate transformations. A complete mathematical method is conveyed to get exact solutions for this convection heat transfer problem. The final solutions are further analyzed through graphical results. The increase in the value of changes the mechanism from non-Newtonian to a Newtonian flow. Moreover, if is increased to infinity, then it becomes a complete Newtonian fluid flow problem. Moreover, the velocity increases with an increasing value of .

Wall shear stress indicators influence the regular hemodynamic conditions in coronary main arterial diseases: cardiovascular abnormalities

Computational hemodynamic (CH) characteristics play a central role in the onset and expansion of atherosclerotic plaques in the coronary main arteries. This study has explored the effects of hemodynamic properties especially coronary arterial wall tangential stresses on various healthy and diseased patient-based coronary artery models based on coronary computed tomography angiography (CCTA) imaging. The key components of the work are the CCTA image acquisition, accurate three-dimensional (3 D) model segmentation, reconstruction, appropriate grid generation, CH simulations, and analysis of the results by using open-source techniques. The CH simulation results have produced hemodynamic variables, including velocity magnitude (VM), mean arterial pressure difference, wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and finally, computational fractional flow reserve (cFFR), that allow the pathophysiological conditions in patient-based coronary models. The VM, mean pressure difference, and WSS indices have yielded consistent simulation results for predicting the severity conditions of coronary diseases. We have compared our cFFR results with the published results and observed that the WSS indices were a good alternative approach for measuring the severity of coronary lesions. The CH results allow a medical expert to estimate the severity of a lumen area and stenosis physiological blood flow conditions in a non-invasive way.

Facile calcium ion-regulated grafting of dense and highly stretched hyaluronan for selective mediation of cancer cells rolling under high-speed flow

The development of materials that selectively mediate the rolling of cancer cells is important for the high-throughput enrichment of high-speed cancer cells. Here we constructed a dense and stretched low molecular weight hyaluronic acid (HA9.6k)-modified surface to selectively promote the rolling of CD44-high cancer cells. The HA surface (calcium ion-regulated HA9.6k surface, Ca-rHA) was fabricated via a calcium ion-regulated method, where calcium ion incorporation induced the shrink of HA9.6k chains to achieve the highest reported grafting density of about 2.73 ± 0.20 × 104 HA chains μm−2. Upon the removal of calcium ions, the dense HA9.6k chains switched to a highly stretched conformation. The high density and flexibility of Ca-rHA bearing abundant binding sites enhanced the rolling of CD44-high cancer cells and reduced the velocity of cells from 1389 µm s−1 to 99 µm s−1 (7%), comparable to that of the physiological rolling event and outperforming traditional grafting-to HA and E-selectin, without causing phenotypic changes. When processing complex samples under high-speed flow, Ca-rHA selectively mediated the rolling of cancer cells and enriched their ratio to peripheral blood mononuclear cells from 1:1 to 15:1. As the only reported artificial biomaterial capable of selectively mediating the rolling of cancer cells under a physiological high-speed flow, Ca-rHA holds promise in enriching intact cells for downstream analysis in the clinics by encouraging the surface-cell contacts. Statement of significanceThe development of materials that selectively mediate the rolling of cancer cells is important for the high-throughput enrichment of cancer cells rolling under high-speed flow, yet is less reported. To selectively promote the rolling of cancer stem cell marker CD44-high cancer cells, a surface with dense and stretched low molecular weight hyaluronic acid (HA9.6k) was constructed. With Ca2+ regulation, HA9.6k chains shrank to achieve the highest reported grafting density of 2.73 ± 0.20 × 104 chains μm−2 and further switched to a highly stretched conformation after the removal of Ca2+ ions. As the only reported artificial biomaterial capable of selectively mediating the rolling of cancer cells under a physiological high-speed flow, this Ca2+-regulated HA9.6k surface holds promise in enriching intact cells for downstream analysis in the clinics.