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. 2026 Jan 30;12(3):1848–1855. doi: 10.1021/acsbiomaterials.5c02111

In Vitro Assessment of Ventricular Catheters with a Multilayered Fibrous Web to Prevent Cellular Occlusion

Seunghyun Lee †,*, Amirhossein Shahriari , Gio Jison , Noah Ramos , Sora Sato , Celine Tran , Leandro Castaneyra-Ruiz , Michael Muhonen
PMCID: PMC12976985  PMID: 41616221

Abstract

Hydrocephalus management generally requires the implantation of a cerebrospinal fluid (CSF) shunt system that includes a ventricular catheter, a mechanical valve to regulate CSF flow, and a distal catheter that diverts the CSF to another site in the body, most commonly the peritoneal cavity. Despite advancements, approximately 40% of these shunts fail within two years, primarily due to catheter occlusion caused by cell attachment and cellular debris. Previous strategies, including polyvinylpyrrolidone (PVP) coatings aimed at reducing bacterial adhesion, have not significantly mitigated occlusion rates in clinical settings. This study explores the development of ventricular shunt catheters with a multilayered fibrous web using electrospinning technique in an effort to mitigate cellular attachment and enhance shunt longevity. Commercial silicone catheters were coated with medical-grade polyurethane material and evaluated for cellular adhesion using human astrocytes and choroid plexus epithelium (ChPE). Cells were visualized through DAPI staining and immunolabeling, and cell counts were quantified using ImageJ. Results demonstrated a significant reduction in cellular adhesion on web-spun catheters compared to uncoated controls, with normalized astrocyte densities decreasing from 37.10 ± 18.44 to 24.39 ± 16.68 [cells/mm2] (p = 0.0329). These findings suggest that web-spun coatings hold promise for improving the reliability and lifespan of shunt systems by mitigating cellular occlusion.

Keywords: hydrocephalus, ventricular shunt, electrospinning, catheter occlusion, cellular adhesion


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Introduction

Hydrocephalus is a complex and debilitating condition characterized by the abnormal accumulation of CSF in the brain, leading to increased intracranial pressure. It affects patients across various age groups, from infants to the elderly, and can be congenital or acquired due to conditions such as spontaneous intracranial hemorrhage, tumors, infections, or trauma. Ventricular shunting, a procedure that involves implanting a device that will divert excess CSF from the brain’s ventricles to another part of the body, remains the most common treatment for hydrocephalus. Despite their life-saving potential, shunts are plagued by high failure rates. Studies have shown that approximately 40% of ventricular shunts in pediatric patients fail within two years of insertion, with over 50% of these failures attributed to ventricular catheter occlusion.

The occlusion of shunt catheters occurs mostly due to the accumulation of cells, including astrocytes, microglia, and peripheral immune cells, including macrophages, along with proteins, lipids, and cellular debris. In addition, the ChPE plays a significant role in catheter obstruction. The catheter occlusion results in CSF flow blockage, resulting in increased intracranial pressure and necessitating shunt revision surgeries. Revision surgeries are not only costly and burdensome but also carry significant risks, including infection, hemorrhage, and neurological injury. These risks underscore the urgent need for innovations that can enhance the longevity and reliability of shunt systems.

Several strategies have been explored to address the issue of catheter occlusion, including the application of surface coatings to reduce bacterial adhesion and biofouling. For example, catheters coated with polyvinylpyrrolidone (PVP) have shown some success in reducing bacterial attachment in vitro. However, clinical studies have not shown a decrease in infection rates with PVP-coated catheters, and one study even reported a significant increase in infection rates. ,− While bacterial infections are a known contributor to shunt failure, they are not the primary cause of catheter occlusion. Cellular attachment, rather than bacterial biofilms, is the predominant factor leading to the blockage of shunt systems. Therefore, there is a growing interest in developing catheter coatings that can effectively prevent cellular adhesion and thus reduce the incidence of catheter occlusion.

In recent years, electrospinning has gained significant attention as a versatile technique for developing advanced surface coatings with antibiofouling properties. This method enables the fabrication of nanofibrous mats composed of ultrafine fibers with high surface area-to-volume ratios and tunable porosity. These characteristics facilitate the formation of coatings that can physically hinder protein adsorption and cell attachment. The interconnected porous structure of electrospun fibers promotes fluid permeability while providing a topographical barrier that discourages cellular adhesion. Electrospun coatings have demonstrated effectiveness in a range of biomedical applications, including wound dressings, tissue engineering scaffolds, and drug delivery systems. Despite their promise, the potential of electrospun coatings to enhance the performance and longevity of ventricular shunt systems in hydrocephalus treatment remains underexplored.

In this study, we present preliminary results on the development of ventricular shunt catheters coated with web-spun fibers and assess their effectiveness in reducing cellular adhesion. Electrospun coatings were applied to commercially available silicone catheters, and in vitro experiments were performed using human astrocytes and ChPE (Figure ). Polyurethane was chosen as the base material of the electrospun fiber due to its current ubiquity in the electrospinning technology and widespread use in medical devices more generally. Astrocytes and ChPE were selected because they are known to contribute to catheter occlusion in hydrocephalus patients. ,,, The ultimate goal of this research is to improve the longevity and reliability of shunt systems by reducing the risk of catheter occlusion, thereby decreasing the need for revision surgeries and improving outcomes for patients with hydrocephalus.

1.

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This study explores a multilayered web-spun coating strategy to prevent cellular adhesion on ventricular catheters. The electrospun fibers create a porous, nonfouling surface that mechanically disrupts cell attachment and tissue ingrowthkey causes of shunt failure in hydrocephalus. By targeting the surface-level cellular mechanisms of occlusion, this approach aims to improve long-term catheter patency and reduce shunt revision rates.

Materials and Methods

Electrospinning of Multilayered Fibrous Web

The base material used for the electrospinning process was Tecothane (Tecothane TT1074A, Lubrizol), a medical-grade thermoplastic polyurethane known for its mechanical robustness and biocompatibility. The solvents used to dissolve Tecothane were N,N-dimethylacetamide (DMAC, Sigma-Aldrich) and tetrahydrofuran (THF, Sigma-Aldrich). The electrospinning solution was prepared by dissolving 25 g of Tecothane in a mixture of 60 g of DMAC and 120 g of THF. The components were mixed until a homogeneous solution was obtained.

The coating process was performed using an electrospinning machine (Spinbox, Bioinicia). Given the device-specific requirements, the electrospinning parameters were experimentally fine-tuned to achieve optimal coating performance. Throughout the coating process, droplet formation and fiber deposition on the device were closely monitored to ensure uniform coating. The multilayered structure was obtained through repeated electrospinning of polyurethane fibers with consistent composition and fiber density, enabling a controlled buildup of coating thickness and mechanical robustness.

The solution was dispensed using a 23-gauge needle (0.5 in. in length) positioned 10 to 15 cm away from the device. Adjustments to the needle position, drip rate (ranging from one drop every 4 to 6 s) and voltage (ranging from 10 to 14 kV) were made in response to observed inconsistencies in coating uniformity, which indicated when either parameter needed to be increased or decreased. The rotational speed was kept constant at 400 rpm.

Catheter Selection and Cell Culture

The catheters used in this study were commercially available silicone catheters with a barium stripe for radiographic visibility (Medtronic, Dublin, Ireland) and BACTISEAL clear ventricular catheters (Integra LifeSciences, NJ, USA). To assess the antifouling properties of the web-spun catheters, we performed in vitro experiments using human astrocytes (N7805–100, Gibco) and ChP (HCPEpiC, ScienCell). The cells were cultured in their respective growth media (Human astrocytes: A1261301, Gibco/Human ChP: EpiCM, ScienCell) and incubated under controlled conditions at 37 °C with 5% CO2. The catheters, both uncoated and web-spun coated, were placed in separate cell culture wells to compare the levels of cellular attachment. Catheters were maintained in cell culture for 7 days, with the medium being refreshed every 48 h. After the incubation period, the catheters were removed from the culture wells and prepared for analysis. ,

This study involved only in vitro experiments using commercially obtained human astrocytes and choroid plexus epithelial cells. These cells were sourced from deidentified donors and purchased from authorized commercial suppliers. Therefore, no institutional IRB approval was required for their use.

Protein Adsorption Assay

For the protein adsorption assay, three experimental conditions were prepared in tissue-culture treated flasks: electrospun web-coated catheters (n = 2), PDMS control catheters (n = 2), and a no-catheter control flask (n = 1). A 100 mL mixed protein solution was prepared by reconstituting fibronectin (0.5 mg/mL) and albumin (0.001 μg/mL) in deionized water at a 1:1 ratio. 20 mL of this solution was dispensed into each flask, and the catheters were incubated for 18 h to allow protein adsorption. Following incubation, immunocytochemistry (ICC) was performed. Samples were washed twice with PBS, fixed in 4% paraformaldehyde for 10 min, and washed again twice in PBS. Catheters were then transferred into 6-well plates to minimize antibody consumption. Primary antibodies included CoraLite 594-conjugated fibronectin polyclonal antibody (rabbit) and mouse monoclonal albumin antibody, each diluted 1:100 in Pierce blocking buffer. A total of 20 mL of primary antibody solution was prepared, with 4 mL allocated per group, and samples were incubated overnight at 4 °C. The next day, samples were washed twice with PBS and incubated with Alexa Fluor 555 secondary antibody (mouse) diluted 1:400 in Pierce blocking buffer for 1 h at room temperature in the dark. After two final PBS washes, catheters and control flasks were imaged using a Keyence fluorescence microscope at excitation/emission wavelengths corresponding to each antibody.

Immunocytochemistry

A standard immunocytochemistry protocol was used to quantify cellular attachment on the catheters. The catheters were rinsed twice with phosphate-buffered saline containing 1% Triton (PBSt), followed by cell fixation with 4% paraformaldehyde in PBS for 7 min. After rerinsing with PBSt, the cells were permeabilized with 5% bovine serum albumin and 1% Triton X-100 for 1 h. Astrocytes were labeled with anti-GFAP (Abcam, ab7260) for 2 h. Cells were washed twice with PBSt, and a secondary antibody (Alexa Fluor 488, Thermo Fisher Scientific, A11034) was applied for 1 h. Finally, cells were stained with DAPI (4′,6-diamidino-2-phenylindole, ab228549, Abcam) (1:5000 in PBS) for nuclear labeling. ChPE cell cultures were labeled with antitransthyretin (TTR) (Dako, A0002) at 1:200 in PBS for 2 h, followed by application of the same secondary antibody and DAPI staining protocol described for the astrocyte cell culture analysis. After confirming appropriate GFAP and TTR immunolabeling for the respective cell types, DAPI staining was used to quantify cell counts on the catheters. The catheter was kept on a 6-well plate submerged in PBS for imaging.

Image Analysis

The catheters were visualized using a fluorescence microscope (EVOS M5000, Invitrogen), specifically focusing on the outer surface of the CSF intake holes to comprehensively analyze coating structure and cell attachment in these critical regions. Images were acquired systematically from these distinct regions and subsequently analyzed using ImageJ (NIH image software) to quantify the density of attached cells. Cell density was calculated as the number of cells per unit area of the catheter surface, excluding the CSF intake hole from the total image area to ensure accurate measurements. Results were normalized to account for variations in imaging regions and experimental conditions as previously reported by our group. , Statistical analysis was conducted to compare cellular attachment between uncoated and web-spun coated catheters, providing insight into the effectiveness of the antifouling coatings.

Assessment of Catheter Pressure and Flow

The hydrodynamic characteristics of the cell-cultured catheters were evaluated through benchtop testing, which involved measuring both flow rate and differential pressure. A 3D ventricular phantom was also used for the benchtop functional test of the devices. ,, This testing was conducted on a separate set of catheters that were maintained under the same astrocyte culture conditions as those used for imaging, but were specifically set aside for pressure and flow testing. An uncoated catheter that was not cultured with cells was used for control. The flow rate was measured at the catheter exit site, while the differential pressure was calculated across the catheter. The testing setup included a syringe pump (Fusion 200-X, Chemyx Inc.), a pressure transducer (PX409-100 GUSBH, Omega, Inc.), and a flow rate sensor (SLF3S-0600F, Sensirion, Inc.). The syringe pump was set to a flow rate of 0.45 mL/min, and the sensors were calibrated to measure differential pressure and flow rate. ,

Statistical Analysis

The mean cell densities for uncoated and web-spun coated catheters were compared using a two-tailed t test to assess the statistical significance of the observed differences. A p-value of less than 0.05 was considered statistically significant. The results were reported as mean ± standard deviation (SD).

Results

SEM analysis revealed that the multilayered electrospun web coating formed a uniform and conformal layer over the catheter surface, including complete coverage of the drainage holes (Figure A). The fibrous web exhibited a randomly oriented, three-dimensional network that was evenly distributed across the surface. At higher magnification, the surface morphology of the coated region showed smooth and continuous fiber deposition without defects or uncoated areas (Figure B). Figure C shows the porous microstructure of the fibrous web, from which pore size and interfiber spacing were quantified to evaluate the uniformity and connectivity of the multilayered architecture. The representative image exhibited a mean pore size of 12.76 ± 3.14 μm. Quantitative analysis from multiple SEM micrographs indicated a mean fiber diameter of 1.58 ± 0.43 μm (Figure D), confirming consistent fiber formation across the coating. Cross-sectional SEM imaging demonstrated that the coating adhered well to the silicone substrate and exhibited a uniform average thickness of 47.33 ± 3.01 μm (Figure H). All values were measured within their respective fields of view, and slight regional variations may occur across different areas of the coating due to local deposition density differences. In the cross-sectional overview (Figure G), minor wrinkling of the fibrous layer was observed near the cut edge, likely due to mechanical deformation during sample sectioning rather than delamination or coating failure.

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Representative SEM images illustrating the morphology and structural characteristics of the multilayered electrospun web coating applied to a silicone barium-stripe catheter (Medtronic, Dublin, Ireland). (A) Low-magnification view showing the catheter drainage hole region uniformly covered by the electrospun web, demonstrating conformal and complete coating deposition. (B) High-magnification image of the coated surface. (C) SEM image displaying the porous microstructure of the fibrous web, with a mean pore size of 12.76 ± 3.14 μm. (D) Detailed view used for fiber-diameter measurement (mean: 1.58 ± 0.43 μm). (E, F) SEM images of the uncoated silicone catheter, showing (E) the bare drainage hole and (F) the smooth native surface. (G) Cross-sectional SEM view confirming complete circumferential coverage; slight wrinkling observed near the cut edge resulted from mechanical deformation during sample preparation, not delamination. (H) Magnified cross-section used for coating-thickness analysis (47.33 ± 3.01 μm). *All quantitative values were obtained from representative fields of view, with slight regional variations expected across the coating.

Collectively, these results confirm that the electrospun coating forms a uniform, multilayered fibrous architecture with stable adhesion to the catheter surfacecharacteristics that support its mechanical integrity and potential for long-term antifouling performance under cerebrospinal fluid flow conditions.

There was a significant reduction in cellular attachment on web-spun coated catheters compared to uncoated catheters in our in vitro model. Fluorescence microscopy images revealed that astrocytes and ChPE adhered more readily to the uncoated silicone catheters, forming dense clusters of cells on the catheter surface. In addition, the CHPE formed a cell monolayer that floats in the media and is capable of penetrating the uncoated catheter holes. In contrast, the web-spun coated catheters showed minimal cellular attachment, with only a few scattered cells observed. Notably, the web-spun coating also acted as a physical barrier, preventing the ChPE monolayer from penetrating and proliferating within the drainage holes of the catheter. Figure illustrates the difference in ChP ingrowth between uncoated and web-spun coated catheters. In the control group, uncoated catheters (A–C) show visible ChP on the outer surface (A), clear ingrowth through a catheter hole (B), and DAPI-stained nuclei surrounding the hole (C). In contrast, the web-spun coated catheters (D–F) exhibit no visible ChP penetration. The coated surface (D) and detailed view of the catheter hole (E) show a clear absence of tissue invasion, while DAPI staining (F) reveals only minimal scattered cells near the hole. To confirm the identity of the cells used, ChP cells cultured at the bottom of the well are shown expressing transthyretin (TTR) in (G).

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ChP ingrowth in control uncoated catheters (A–C) compared to web-spun catheters (D–F). All samples were based on silicone barium-stripe catheters (Medtronic, Dublin, Ireland). (A) Uncoated catheter with ChP. (B) Detail of a catheter hole showing ChP ingrowth. (C) DAPI-stained cells surrounding the hole, with some faint autofluorescence originating from the PDMS. (D) Silicone catheter with web-spun coating. (E) Detail of a catheter hole. (F) DAPI-stained cells surrounding the hole, with some faint autofluorescence originating from the PDMS. (G) Representative image of ChPE attached to the bottom of the cell culture well, expressing TTR to confirm the cell type tested. (The dotted line indicates the location of the catheter hole.)

Quantitative analysis was conducted to evaluate astrocyte attachment and determine the effect of the web-spun coating on cell adherence (Figure ). Individual data points from each sample are shown to illustrate data variability and distribution. Statistical comparison using an unpaired two-tailed t-test revealed a significant reduction in astrocyte attachment on web-spun coated catheters compared to uncoated controls (t = 2.219, df = 36, p = 0.0329). The mean cell density on web-spun coated catheters was 24.39 ± 16.68 [cells/mm2], whereas uncoated control catheters exhibited 37.10 ± 18.44 [cells/mm2]. An F-test confirmed that variances between groups were not significantly different (F = 1.222, p = 0.683), supporting the use of a standard unpaired t-test.

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Astrocyte ingrowth in web spun vs control catheters. All samples were based on silicone barium-stripe catheters (Medtronic, Dublin, Ireland). (A) Significant cellular attachment around the catheter hole. (B) Fewer cells attached to the web-spun coated catheter. (C) Quantification of cell attachment, shown as individual data points (Control: n = 20; Fibrous web: n = 18). Data are presented as mean ± SD and analyzed using an unpaired two-tailed t-test (t = 2.219, df = 36, p = 0.0329). Mean cell attachment was significantly lower in fibrous web-coated catheters (24.39 ± 16.68 SD) compared with controls (37.10 ± 18.44 SD). Variances were not significantly different (F = 1.222, p = 0.683). (D) In vitro human astrocytes labeled with anti-GFAP, confirming the cell type tested.

Microscopic assessment revealed clear qualitative differences in protein presence between untreated and web-spun catheter surfaces (Figure ). On bare silicone substrates (A–C), protein deposits were readily identifiable across the surface, frequently appearing as localized aggregates or continuous patches along the catheter wall. These morphologies suggest that the native catheter surface readily supports protein adhesion and spreading. In contrast, electrospun web-coated catheters (D–F) exhibited sparse or indistinct protein traces, with minimal detectable surface coverage. The discontinuous and faint appearance of protein residues indicates that the fibrous surface architecture disrupts uniform protein settlement and limits stable adsorption sites. These findings suggest that the electrospun modification substantially reduces the initial presence of adherent proteinsan early indicator of antifouling potentialindependent of staining intensity.

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Protein presence on untreated and electrospun web-coated catheter surfaces (BACTISEAL clear ventricular catheters (Integra LifeSciences, NJ, USA)). (A–C) Untreated catheters show identifiable protein deposition distributed across the surface, appearing as visible clusters or localized surface coverage. (D–F) Electrospun web-coated catheters under identical exposure conditions reveal minimal detectable protein presence, with only sparse traces at isolated regions. These qualitative observations indicate a substantial reduction in protein residency on web-spun surfaces compared to bare silicone substrates.

Flow testing revealed a linear relationship between hydrodynamic pressure and flow rate in web-spun coated catheters, indicating that the coating does not obstruct CSF movement (Figure ). Using a syringe pump set to 0.45 mL/min, both coated and control catheters maintained consistent flow profiles, with the coated group showing no deviation from expected pressure–flow behavior. These results confirm that the fibrous web structure permits unimpeded CSF flow and does not compromise catheter performance.

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Pressure (P)–Flow (Q) comparison between web-spun coated vs control catheters. (A) Experimental setup for flow testing. The flow was injected by a syringe pump at 0.45 mL/min. (B, C) The flow test results demonstrated a linear hydrodynamic pressure-flow (P-Q) relationship for the web-spun coated catheters, indicating that the coated web structure does not interfere with CSF flow.

Discussion

The findings of this study highlight the potential of web-spun coatings to address one of the most persistent challenges in the treatment of hydrocephalus: catheter occlusion driven by cellular adhesion and tissue ingrowth. In vitro results demonstrated markedly reduced adhesion of astrocytes and ChPE on web-spun coated catheters compared to uncoated silicone controls. Fluorescence microscopy revealed dense, continuous cell clusters on uncoated surfaces, whereas coated catheters exhibited only minimal and spatially scattered cell presence. Complementary protein adsorption assays further support this trend, showing substantially reduced detectable protein presence on web-spun catheters. Given that adsorbed protein layers act as conditioning films that mediate cell anchoring and spreading, suppression of early protein deposition likely contributes to the decrease in cellular adhesion.

Importantly, the mechanism underlying this antiadhesive behavior appears to be rooted in the biophysical differences between catheter surfaces. Unlike smooth silicone surfaces that facilitate cellular spreading and focal adhesion formation, the irregular, porous structure of the electrospun fibers creates a topography that is inherently nonconducive to stable cell attachment. By limiting both initial protein fouling and subsequent cell–surface interactions, the electrospun web coating interrupts multiple stages of the fouling cascade, suggesting a promising surface-engineering strategy to mitigate shunt occlusion.

At the cellular level, the discontinuous contact points and high curvature of individual electrospun fibers significantly alter how cells perceive and engage with the substrate. On smooth, planar surfaces, cells form continuous adhesive zones where integrins cluster into large, stable focal adhesion complexes, which anchor actin stress fibers and generate contractile tension through RhoA/ROCK signaling. The RhoA/ROCK pathway regulates actin–myosin contractility and traction forces, enabling cells to maintain shape, exert tension, and strengthen adhesion. In contrast, fibrous surfaces provide intermittent nanoscale anchoring points, preventing integrins from clustering efficiently. This leads to the formation of smaller, more transient focal adhesions and suppresses the activation of focal adhesion kinase (FAK)a key mechanotransduction mediator that links integrin engagement to downstream cytoskeletal organization and cell survival signaling.

The high local curvature of nanofibers further reduces the effective area for integrin binding and forces the cell membrane into a curved conformation, mechanically destabilizing focal adhesion formation. As a result, the downstream FAK–RhoA–ROCK signaling axis is insufficiently activated, leading to reduced actomyosin contractility and diminished cytoskeletal tension. Cells under these conditions cannot generate the traction forces required for spreading, migration, or stable attachment. This mechanobiological inhibition ultimately limits both adhesion stability and proliferation on the electrospun web surface.

Additionally, the random orientation and nanoscale diameter of the fibers impose topographical steric hindrance, restricting the stabilization of lamellipodia and filopodia necessary for firm surface anchorage. Similar inhibitory effects of nanoscale curvature and spatial discontinuity on filopodia dynamics and protrusive activity have been reported in fibroblasts and epithelial cells, where reduced membrane adhesion and actin polymerization impair the protrusive stabilization of cell–substrate contacts. , Together with the disruption of focal adhesion maturation described above, these structural and mechanobiological factors further prevent the sustained cytoskeletal organization required for effective surface colonization. This mechanistic framework coherently explains the reduced attachment of both astrocyte and ChPE cells observed on the web-coated surfaces. Although these two cell types differ in their physiological functions, both rely on integrin-mediated adhesion and actin cytoskeletal organization that are highly sensitive to surface topography and stiffness. Therefore, the inhibition of focal adhesion maturation and cytoskeletal tension on the fibrous surface provides a unified mechanistic basis for the observed reduction in cell attachment.

Importantly, the web-spun coating not only reduced surface adhesion but also acted as a physical barrier that prevented ChPE from penetrating and proliferating within the catheter holesa critical site of obstruction in clinical settings. , The dense, fibrous structure of the coating likely prevents ChPE from physically penetrating the openings, limiting their ability to anchor, migrate or extend into the catheter interior. By blocking tissue ingrowth into the catheter holes, the web-spun coating supports continuous CSF drainage and reduces the risk of shunt obstruction.

Taken together, these findings suggest that the antifouling effect arises from both mechanical and mechanobiological interference, where the fibrous architecture disrupts focal adhesion maturation and mechanotransductive signaling while simultaneously providing a physical barrier against cell infiltration. This dual mechanism offers a passive yet effective strategy for maintaining long-term shunt patency, potentially reducing the need for revision surgeries and associated complications such as infection, neurological injury, and increased patient morbidity.

While the in vitro results are encouraging, there are several limitations to consider. This pilot study does not fully reflect the complex immune responses of the central nervous system to implanted devices, nor does it account for the shear stress at CSF intake holes resulting from in vivo CSF flow. Furthermore, the long-term stability of the multilayered fibrous web coating on the catheter was not evaluated. Importantly, the cellular analysis was limited to astrocytes and ChPE; however, other cell typesparticularly microglia and infiltrating peripheral macrophagesare critical mediators of neuroinflammation and may significantly contribute to shunt occlusion. Future studies should explicitly investigate these additional immune cell populations to fully understand the biological response to the implant.

Environmental factors, such as static electricity, humidity and temperature, significantly influenced the electrospinning process used for coating application. Precise adjustments to these parameters were necessary to accommodate the specific dimensions and material properties of the device, given the high sensitivity of electrospinning performance to environmental changes. These dependencies underscore the need for optimized and controlled coating conditions to achieve reproducibility and maintain consistent quality across varied experimental settings. Additionally, the durability of the web-spun coating over extended periods remains to be evaluated, and future studies should assess the coating’s resistance to wear and degradation in dynamic physiological conditions.

Future research should include in vivo testing using hydrocephalus animal models to assess the performance of web-spun coated catheters in more realistic biological settings. A broader examination of cell types and inflammatory markers would provide a more comprehensive understanding of the coating’s antifouling capabilities. Long-term durability studies are needed to evaluate the coating’s mechanical and chemical stability over time. Additionally, exploring the potential for combining web-spun coatings with antimicrobial agents could offer a more thorough approach to prevent both bacterial and cellular biofouling.

Conclusion

This work demonstrates that web-spun surface modification holds promise as a strategy to reduce shunt obstruction. Web-coated catheters exhibited markedly lower protein deposition and decreased attachment of astrocytes and ChPE compared to uncoated controls, indicating attenuation of the early fouling events that drive cellular ingrowth. These findings suggest that web-spun coatings could enhance the performance and longevity of shunt systems used in the treatment of hydrocephalus, thereby reducing the frequency of shunt revisions and improving patient outcomes.

Future work should focus on validating these results in vivo and exploring the clinical applications of web-spun coatings for the treatment of hydrocephalus. Establishing their efficacy and biocompatibility in physiological settings may pave the way for a novel therapeutic approach, offering improved durability and reliability over current treatment modalities for hydrocephalus.

Acknowledgments

This work was supported by the CHOC Children’s Research Institute. We gratefully acknowledge NV Medtech Inc. for their assistance in fabricating and applying the electrospun web coatings on the catheter samples used in this study.

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These authors contributed equally to this work (L.C.-R. and M.M.).

The authors declare no competing financial interest.

References

  1. Isaacs A. M., Riva-Cambrin J., Yavin D.. et al. Age-specific global epidemiology of hydrocephalus: Systematic review, metanalysis and global birth surveillance. PLoS One. 2018;13(10):e0204926. doi: 10.1371/journal.pone.0204926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Rekate H. L.. A contemporary definition and classification of hydrocephalus. Semin Pediatr Neurol. 2009;16(1):9–15. doi: 10.1016/j.spen.2009.01.002. [DOI] [PubMed] [Google Scholar]
  3. Stone J. J., Walker C. T., Jacobson M., Phillips V., Silberstein H. J.. Revision rate of pediatric ventriculoperitoneal shunts after 15 years. J. Neurosurg Pediatr. 2013;11(1):15–9. doi: 10.3171/2012.9.PEDS1298. [DOI] [PubMed] [Google Scholar]
  4. Kulkarni A. V., Riva-Cambrin J., Butler J.. et al. Outcomes of CSF shunting in children: comparison of Hydrocephalus Clinical Research Network cohort with historical controls clinical article. J. Neurosurg Pediatr. 2013;12(4):334–8. doi: 10.3171/2013.7.PEDS12637. [DOI] [PubMed] [Google Scholar]
  5. Hanak B. W., Bonow R. H., Harris C. A., Browd S. R.. Cerebrospinal Fluid Shunting Complications in Children. Pediatr Neurosurg. 2017;52(6):381–400. doi: 10.1159/000452840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hanak B. W., Ross E. F., Harris C. A., Browd S. R., Shain W.. Toward a better understanding of the cellular basis for cerebrospinal fluid shunt obstruction: report on the construction of a bank of explanted hydrocephalus devices. J. Neurosurg Pediatr. 2016;18(2):213–23. doi: 10.3171/2016.2.PEDS15531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hariharan P., Sondheimer J., Petroj A.. et al. A multicenter retrospective study of heterogeneous tissue aggregates obstructing ventricular catheters explanted from patients with hydrocephalus. Fluids and Barriers of the CNS. 2021;18(1):33. doi: 10.1186/s12987-021-00262-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Galarza M., Giménez A., Amigó J. M.. et al. Next generation of ventricular catheters for hydrocephalus based on parametric designs. Childs Nerv Syst. 2018;34(2):267–276. doi: 10.1007/s00381-017-3565-0. [DOI] [PubMed] [Google Scholar]
  9. Hanak B. W., Hsieh C. Y., Donaldson W., Browd S. R., Lau K. K. S., Shain W.. Reduced cell attachment to poly­(2-hydroxyethyl methacrylate)-coated ventricular catheters in vitro. J. Biomed Mater. Res. B Appl. Biomater. 2018;106(3):1268–1279. doi: 10.1002/jbm.b.33915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harris C. A., McAllister J. P. 2nd. What we should know about the cellular and tissue response causing catheter obstruction in the treatment of hydrocephalus. Neurosurgery. 2012;70(6):1589–601. doi: 10.1227/NEU.0b013e318244695f. [DOI] [PubMed] [Google Scholar]
  11. Portnoy H. D., Schulte R. R., Fox J. L., Croissant P. D., Tripp L.. Anti-siphon and reversible occlusion valves for shunting in hydrocephalus and preventing post-shunt subdural hematomas. J. Neurosurg. 1973;38(6):729–38. doi: 10.3171/jns.1973.38.6.0729. [DOI] [PubMed] [Google Scholar]
  12. Tschan C. A., Antes S., Huthmann A., Vulcu S., Oertel J., Wagner W.. Overcoming CSF overdrainage with the adjustable gravitational valve proSA. Acta Neurochir (Wien) 2014;156(4):767–76. doi: 10.1007/s00701-013-1934-3. [DOI] [PubMed] [Google Scholar]
  13. Gebert A. F., Schulz M., Schwarz K., Thomale U. W.. Long-term survival rates of gravity-assisted, adjustable differential pressure valves in infants with hydrocephalus. J. Neurosurg Pediatr. 2016;17(5):544–51. doi: 10.3171/2015.10.PEDS15328. [DOI] [PubMed] [Google Scholar]
  14. Bhardwaj N., Kundu S. C.. Electrospinning: A fascinating fiber fabrication technique. Biotechnology Advances. 2010;28(3):325–347. doi: 10.1016/j.biotechadv.2010.01.004. [DOI] [PubMed] [Google Scholar]
  15. Xue J., Wu T., Dai Y., Xia Y.. Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications. Chem. Rev. 2019;119(8):5298–5415. doi: 10.1021/acs.chemrev.8b00593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Agarwal S., Wendorff J. H., Greiner A.. Use of electrospinning technique for biomedical applications. Polymer. 2008;49(26):5603–5621. doi: 10.1016/j.polymer.2008.09.014. [DOI] [Google Scholar]
  17. Wang X., Ding B., Li B.. Biomimetic electrospun nanofibrous structures for tissue engineering. Mater. Today. 2013;16(6):229–241. doi: 10.1016/j.mattod.2013.06.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Li D., Xia Y.. Electrospinning of Nanofibers: Reinventing the Wheel? Adv. Mater. 2004;16(14):1151–1170. doi: 10.1002/adma.200400719. [DOI] [Google Scholar]
  19. Ramakrishna S., Fujihara K., Teo W.-E., Yong T., Ma Z., Ramaseshan R.. Electrospun nanofibers: solving global issues. Mater. Today. 2006;9(3):40–50. doi: 10.1016/S1369-7021(06)71389-X. [DOI] [Google Scholar]
  20. Greiner A., Wendorff J. H.. Electrospinning: A Fascinating Method for the Preparation of Ultrathin Fibers. Angew. Chem., Int. Ed. 2007;46(30):5670–5703. doi: 10.1002/anie.200604646. [DOI] [PubMed] [Google Scholar]
  21. Ji W., Yang F., van den Beucken J. J.. et al. Fibrous scaffolds loaded with protein prepared by blend or coaxial electrospinning. Acta Biomater. 2010;6(11):4199–207. doi: 10.1016/j.actbio.2010.05.025. [DOI] [PubMed] [Google Scholar]
  22. Liddelow S. A.. Development of the choroid plexus and blood-CSF barrier. Front Neurosci. 2015;9:32. doi: 10.3389/fnins.2015.00032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Orešković D., Radoš M., Klarica M.. Role of choroid plexus in cerebrospinal fluid hydrodynamics. Neuroscience. 2017;354:69–87. doi: 10.1016/j.neuroscience.2017.04.025. [DOI] [PubMed] [Google Scholar]
  24. Lee S., Ledbetter J., Davies J., Romero B., Muhonen M., Castaneyra-Ruiz L.. Polyvinylpyrrolidone-coated catheters decrease choroid plexus adhesion and improve flow/pressure performance in an in vitro model of hydrocephalus. Childs Nerv Syst. 2024;40(1):115–121. doi: 10.1007/s00381-023-06058-0. [DOI] [PubMed] [Google Scholar]
  25. Castañeyra-Ruiz L., Lee S., Chan A. Y.. Polyvinylpyrrolidone-Coated Catheters Decrease Astrocyte Adhesion and Improve Flow/Pressure Performance in an Invitro Model of Hydrocephalus. Children (Basel) 2023;10(1):18. doi: 10.3390/children10010018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Harris C. A., Resau J. H., Hudson E. A., West R. A., Moon C., Black A. D., McAllister J. P.. Reduction of protein adsorption and macrophage and astrocyte adhesion on ventricular catheters by polyethylene glycol and N-acetyl-L-cysteine. J. Biomed Mater. Res. A. 2011;98(3):425–33. doi: 10.1002/jbm.a.33130. [DOI] [PubMed] [Google Scholar]
  27. Castaneyra-Ruiz L., McAllister J. P. 2nd, Morales D. M., Brody S. L., Isaacs A. M., Limbrick D. D. Jr.. Preterm intraventricular hemorrhage in vitro: modeling the cytopathology of the ventricular zone. Fluids Barriers CNS. 2020;17(1):46. doi: 10.1186/s12987-020-00210-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lee S., Vinzani M., Romero B., Chan A. Y., Castañeyra-Ruiz L., Muhonen M.. Partial Obstruction of Ventricular Catheters Affects Performance in a New Catheter Obstruction Model of Hydrocephalus. Children (Basel) 2022;9(10):1453. doi: 10.3390/children9101453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lee S., Castañeyra-Ruiz L., Sato S.. et al. 3D-printed microfluidic device for cerebrospinal fluid diversion: Design, characterization, and in vitro evaluation of an alternative shunting device. Sens. Actuators, B. 2025;425:136961. doi: 10.1016/j.snb.2024.136961. [DOI] [Google Scholar]
  30. Lee S., Bristol R. E., Preul M. C., Chae J.. Three-Dimensionally Printed Microelectromechanical-System Hydrogel Valve for Communicating Hydrocephalus. ACS Sens. 2020;5(5):1398–1404. doi: 10.1021/acssensors.0c00181. [DOI] [PubMed] [Google Scholar]
  31. Dalby M. J., Gadegaard N., Tare R.. et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater. 2007;6(12):997–1003. doi: 10.1038/nmat2013. [DOI] [PubMed] [Google Scholar]
  32. Kim D.-H., Han K., Gupta K., Kwon K. W., Suh K.-Y., Levchenko A.. Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. Biomaterials. 2009;30(29):5433–5444. doi: 10.1016/j.biomaterials.2009.06.042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wozniak M. A., Chen C. S.. Mechanotransduction in development: a growing role for contractility. Nat. Rev. Mol. Cell Biol. 2009;10(1):34–43. doi: 10.1038/nrm2592. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ventre M., Causa F., Netti P. A.. Determinants of cell-material crosstalk at the interface: towards engineering of cell instructive materials. J. R Soc. Interface. 2012;9(74):2017–32. doi: 10.1098/rsif.2012.0308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Oh S., Brammer K. S., Li Y. S.. et al. Stem cell fate dictated solely by altered nanotube dimension. Proc. Natl. Acad. Sci. U. S. A. 2009;106(7):2130–5. doi: 10.1073/pnas.0813200106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. McNamara L. E., McMurray R. J., Biggs M. J., Kantawong F., Oreffo R. O., Dalby M. J.. Nanotopographical control of stem cell differentiation. J. Tissue Eng. 2010;1:120623. doi: 10.4061/2010/120623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Xie J., MacEwan M. R., Schwartz A. G., Xia Y.. Electrospun nanofibers for neural tissue engineering. Nanoscale. 2010;2(1):35–44. doi: 10.1039/B9NR00243J. [DOI] [PubMed] [Google Scholar]
  38. Bettinger C. J., Langer R., Borenstein J. T.. Engineering Substrate Topography at the Micro- and Nanoscale to Control Cell Function. Angew. Chem., Int. Ed. 2009;48(30):5406–5415. doi: 10.1002/anie.200805179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Bashur C., Dahlgren L., Goldstein A.. Effect of fiber diameter and orientation on fibroblast morphology and proliferation on electrospun poly (D, L-lactic-co-glycolic acid) meshes. Biomaterials. 2006;27:5681–8. doi: 10.1016/j.biomaterials.2006.07.005. [DOI] [PubMed] [Google Scholar]
  40. Discher D. E., Janmey P., Wang Y. L.. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;310(5751):1139–43. doi: 10.1126/science.1116995. [DOI] [PubMed] [Google Scholar]
  41. Yao L., Haas T., Guiseppi-Elie A., Bowlin G., Simpson D., Wnek G.. Electrospinning and Stabilization of Fully Hydrolyzed Poly­(Vinyl Alcohol) Fibers. Chemistry of Materials - CHEM MATER. 2003;15:1860. doi: 10.1021/cm0210795. [DOI] [Google Scholar]
  42. Gower D. J., Watson D., Harper D.. e-PTFE ventricular shunt catheters. Neurosurgery. 1992;31(6):1132–5. doi: 10.1227/00006123-199212000-00024. [DOI] [PubMed] [Google Scholar]
  43. Romero B., Jison G., Self S.. et al. Absence of immunoreaction and cellular adhesion in a polyvinylpyrrolidone-coated ventricular catheter with choroid plexus obstruction: A case report. Surg Neurol Int. 2025;16:65. doi: 10.25259/SNI_970_2024. [DOI] [PMC free article] [PubMed] [Google Scholar]

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