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A light-reflecting balloon catheter for atraumatic tissue defect repair

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Science Translational Medicine  23 Sep 2015:
Vol. 7, Issue 306, pp. 306ra149
DOI: 10.1126/scitranslmed.aaa2406
  • Fig. 1. A transcatheter light-reflecting technology that delivers and activates a photocurable adhesive.

    (A) Artistic representation of potential applications for the device, including repair of perforated peptic ulcer, abdominal wall, and intracardiac defects. (B) Schematics showing reflection of light rays inside the balloon onto a precoated patch and a simulation of reflected rays. (C) Functional components of the device include a proximal balloon, an intermediate shaft, a distal balloon with a secondary outer balloon and removable sutures for temporary patch/balloon coupling, and a patch with a photocurable adhesive. (D) Catheter shaft with functional components loaded and ready for delivery. (E and F) Procedural steps from side (E) and front (F) views on a tissue sample: delivery into cavity, patch release, balloon inflation, adhesive activation, and removal of the device after deploying the adherent patch. DB, distal balloon; PB, proximal balloon; P, patch.

  • Fig. 2. Development and characterization of a light-reflective flexible medical balloon.

    (A) Photo and schematic showing coated urethane test specimen mounted at a 45° angle to a light source with a lens and detector. (B) Reflectivity (as a percentage of a UV-enhanced mirror) for urethane samples coated with aluminum (Al) and palladium (Pd) with and without plasma pretreatment. Data are medians and interquartile ranges (n = 4). **P = 0.0022 compared to mirror. (C) Reflectivity (as a percentage of a UV-enhanced mirror) with outer protective coatings of urethane, parylene, and gold on plasma-treated, aluminum-coated balloons. Data are medians and interquartile ranges (n = 4). *P = 0.0197 compared to mirror. For (B) and (C), P value was determined with a Kruskal-Wallis test and Dunn’s multiple comparison post hoc test. (D) Schematic of sputter coating: direct current (DC) was applied to the Al target cathode in argon plasma, Al particles were deposited on the anode, coating the balloons. (E) Urethane balloons on the rotating mount in the sputter chamber during the deposition process. (F) Coated balloons. (G) Schematic showing the layers of the optimized reflective coated balloons: a protective outer urethane layer, 100 nm of aluminum, and plasma-treated urethane balloon.

  • Fig. 3. Optimization of a low-profile fiber optic for light dispersion.

    (A and B) Light ray model and intensity map on the patch/septum for a flat-tip fiber (A) and a conical fiber (20° half-angle) (B) with an insertion distance into the balloon of 0, 10, and 18.5 mm. The images on the top of each panel trace a sample of random rays. The simulations in the bottom of each panel are based on 108 rays for a total launched power of 1 W. The efficiency calculations assumed that 100% of the light was available in the fiber before the light was launched into the catheter distances of 0, 10, and 18.5 mm. (C) Efficiency (total power at detector divided by input power) of flat and conical tips. Data are the results of the simulation (n = 1 for each tip shape) at each catheter insertion distance. (D) Sculpted conical fiber optic tip and corresponding dimensions.

  • Fig. 4. Demonstration of potential clinical applicability in vivo in rats and ex vivo in porcine heart, abdomen, and stomach.

    (A) Pull-off force of patch attached subcutaneously by HLAA or suture on rodent abdomen at different time points. Data are medians and interquartile ranges (n = 5). P = 0.6029 between the device and sutures; P = 0.0077 for the effect of time, two-way ANOVA (analysis of variance). (B) Schematic of pull-off testing on a mechanical tester and adhesion pull-off forces for explanted pig heart, abdominal wall, and stomach tissues. Data are represented by a scatterplot with median and interquartile range displayed (n = 3). P value was determined by a Kruskal-Wallis analysis with Dunn’s multiple comparison test. (C) Proof of concept of ventricular septal defect closure in pigs. From left: schematic of the device securing patch to porcine left ventricular septal wall, pressurized water-tank setup, the device activating the adhesive on bench, and adherent patch after device removal. (D) Proof of concept of device functionality on porcine abdominal wall. From left: schematic of the device fixing patch to back of abdominal wall, delivery, activation, and removal of the device leaving adhered patch. (E) Proof of concept of NOTES access for perforated gastric ulcer repair in pigs. From left: concept of mouth to esophagus access, device delivery, activation and removal of device with additional adhesive to seal the residual defect, allowing filling of the porcine stomach without leakage.

  • Fig. 5. In vivo inflammatory response in a rodent model and shear and cyclical testing.

    (A) Applying the patch to the rat heart using the miniaturized device. (B and C) Degree of fibrosis/inflammation in rat heart and abdomen (abd) samples in response to patches applied by the device or with sutures, as determined by a blinded pathology expert. Data are means and ranges (n = 2 per group at each time point). (D) Representative histology images 1 day after surgery for heart and abdomen, as well as 1 week after surgery for abdomen and 2 weeks after surgery for the heart. PGSU patch denoted by “P” or arrow; C, capsule. Black scale bar, 1 mm; white scale bar, 125 μm. In one case, the patch came off during processing. (E) Shear test setup is shown on the left. Data are in a scatterplot with median and interquartile ranges (n = 5 tissue samples with adhered patches). (F) Test setup and results for cyclical testing of patch/adhesive with tissue (100 compressive cycles).

  • Fig. 6. Characterization of the device for cardiac-specific applications.

    (A) Schematic showing endocardial and epicardial surface of the rat heart tissue and apparatus used for pull-off force testing with a mechanical tester and results of pull-off force testing on endocardium and epicardium. Data are a box-and-whiskers plot with median, quartiles, and max and min values. P value was determined using a two-tailed Mann-Whitney test (n = 17 tissue/patch samples). (B) Test setup for burst pressure testing showing pressurized chamber (at pressure P1) and external pressure P2. Patch/hole ratio is the ratio between patch and defect diameter. Data are represented by a scatterplot with median and 25 and 75% quartiles (n = 3 to 6 tissue samples). (C) Test setup for varying preload. Data are represented by a scatterplot with median and interquartile range (n = 3 tissue samples). P value was determined by a Kruskal-Wallis test with Dunn’s multiple comparison post hoc test.

  • Fig. 7. Proof of concept of the device reducing porcine ventricular septal defect (VSD) in vivo.

    (A) A schematic of the device in a cross section of the heart. (B) Access for in vivo procedure showing anterolateral thoracotomy, position of echo probe, and RV access through a purse-string suture, which is used to maintain a seal around the device during the procedure. (C) Echocardiograph showing visualization of device insertion into the LV (catheter shaft demarcated by blue dashed lines). (D) Echocardiograph showing the two inflated balloons (demarcated by blue dashed lines). (E) Echocardiograph with Doppler flow before patch implantation showing an average VSD diameter of 5.5 mm. (F) Echocardiograph with Doppler flow after patch implantation showing an average VSD diameter of 1.4 mm. (G) Echocardiograph of the patch on the septum VSD. (H) Patch adhered on the heart after the procedure.

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/7/306/306ra149/DC1

    Materials and Methods

    Fig. S1. Handle component design.

    Fig. S2. Decoupling mechanism for handle components.

    Fig. S3. Engineering drawing of the raster rod.

    Fig. S4. Engineering drawing of the slider sleeve.

    Fig. S5. Engineering drawing of the handle body.

    Fig. S6. Energy-dispersive electron spectrometry.

    Fig. S7. Adhesion testing of the aluminum deposition process on parylene-coated urethane samples.

    Fig. S8. The inflated balloon approximates an axicon for light simulations.

    Fig. S9. Light ray analysis for flat- and conical-tipped fibers.

    Fig. S10. A modified catheter for direct application of light.

    Fig. S11. Demonstration of transvascular access in the porcine heart.

    Fig. S12. The patch adheres to the endocardial tissue.

    Table S1. Reflectivity with various coatings with or without plasma pretreatment.

    Table S2. Reflectivity with various outer coatings.

    Table S3. Efficiency for flat and conical tip fiber.

    Table S4. Pull-off forces in vivo for rat tissues on subcutaneous abdomen.

    Table S5. Pull-off forces for ex vivo porcine tissues (endocardium, abdominal wall, and stomach).

    Table S6. Pull-off forces for endocardium and epicardium.

    Table S7. Burst pressures for case 1 and case 2 for various patch/defect ratios.

    Table S8. Pull-off forces for different preloads.

    Movie S1. Overview of device functioning.

    Movie S2. Light analysis as conical tip is moved into the balloon.

    Movie S3. Doppler flow before and after VSD closure.

    Movie S4. Patch deployment in vitro and in vivo.

    Movie S5. Patch stabilization in vitro and in vivo.

    Movie S6. Adhered patch in vivo in beating heart.

    Reference (38)

  • Supplementary Material for:

    A light-reflecting balloon catheter for atraumatic tissue defect repair

    Ellen T. Roche, Assunta Fabozzo, Yuhan Lee, Panagiotis Polygerinos, Ingeborg Friehs, Lucia Schuster, William Whyte, Alejandra Maria Casar Berazaluce, Alejandra Bueno, Nora Lang, Maria J. N. Pereira, Eric Feins, Steven Wasserman, Eoin D. O'Cearbhaill, Nikolay V. Vasilyev, David J. Mooney, Jeffrey M. Karp, Pedro J. del Nido,* Conor J. Walsh*

    *Corresponding author. E-mail: walsh{at}seas.harvard.edu (C.J.W.); pedro.delnido{at}cardio.chboston.org (P.J.d.N.)

    Published 23 September 2015, Sci. Transl. Med. 7, 306ra149 (2015)
    DOI: 10.1126/scitranslmed.aaa2406

    This PDF file includes:

    • Materials and Methods
    • Fig. S1. Handle component design.
    • Fig. S2. Decoupling mechanism for handle components.
    • Fig. S3. Engineering drawing of the raster rod.
    • Fig. S4. Engineering drawing of the slider sleeve.
    • Fig. S5. Engineering drawing of the handle body.
    • Fig. S6. Energy-dispersive electron spectrometry.
    • Fig. S7. Adhesion testing of the aluminum deposition process on parylene-coated urethane samples.
    • Fig. S8. The inflated balloon approximates an axicon for light simulations.
    • Fig. S9. Light ray analysis for flat- and conical-tipped fibers.
    • Fig. S10. A modified catheter for direct application of light.
    • Fig. S11. Demonstration of transvascular access in the porcine heart.
    • Fig. S12. The patch adheres to the endocardial tissue.
    • Table S1. Reflectivity with various coatings with or without plasma pretreatment.
    • Table S2. Reflectivity with various outer coatings.
    • Table S3. Efficiency for flat and conical tip fiber.
    • Table S4. Pull-off forces in vivo for rat tissues on subcutaneous abdomen.
    • Table S5. Pull-off forces for ex vivo porcine tissues (endocardium, abdominal wall, and stomach).
    • Table S6. Pull-off forces for endocardium and epicardium.
    • Table S7. Burst pressures for case 1 and case 2 for various patch/defect ratios.
    • Table S8. Pull-off forces for different preloads.
    • Legends for movies S1 to S6
    • Reference (38)

    [Download PDF]

    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.mp4 format). Overview of device functioning.
    • Movie S2 (.mp4 format). Light analysis as conical tip is moved into the balloon.
    • Movie S3 (.mp4 format). Doppler flow before and after VSD closure.
    • Movie S4 (.mp4 format). Patch deployment in vitro and in vivo.
    • Movie S5 (.mp4 format). Patch stabilization in vitro and in vivo.
    • Movie S6 (.mp4 format). Adhered patch in vivo in beating heart.

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