Research ArticleMEDICAL ROBOTS

An actuatable soft reservoir modulates host foreign body response

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Science Robotics  28 Aug 2019:
Vol. 4, Issue 33, eaax7043
DOI: 10.1126/scirobotics.aax7043
  • Fig. 1 An overview of the device and the proposed mechanism of action.

    (A) Implantable system showing a side-by-side implantation of a control and actuation group. (B) Nonporous configuration of the DSR for foreign body modulation for implantable devices. (C) Porous configuration of the DSR for therapy delivery.

  • Fig. 2 An overview of the configuration of the DSR devices.

    (A) Nonporous configuration for foreign body modulation of implantable devices. (B) Porous configuration for therapy delivery.

  • Fig. 3 Computational and experimental characterization.

    (A) Stress/strain plots for porous and nonporous thermoplastic urethane specimens. (B) Fitting of the porous data to the Ogden hyperelastic model. (C) Mises stress contour plots for the overall device, and the lower membrane (top-down and side view where the broken red line illustrates deflection, δ, of the membrane). (D) Maximum in-plane strain for the overall device and the lower membrane (top-down and side view). (E) Experimental cyclical force measurements of two actuation regimes (regime 1, 1 psi at 1 Hz; regime 2, 2 psi at 1 Hz), and finite element predicted force for each. (F) Relationship between input pressure and actuation force as measured experimentally and predicted with FEA. (G) Burst failure of DSRs after actuating at regime 1 or regime 2 for 100,000 cycles. n = 6 per group, data are mean ± SD, P > 0.05. (H) 3D smoothed particle hydrodynamic model showing the direction of fluid flow surrounding a DSR during actuation and (I) 2D slice of model to illustrate direction and magnitude of fluid flow at the area of maximum deflection.

  • Fig. 4 DSR reduces the fibrous capsule thickness in vivo.

    (A) Timeline for in vivo studies for nonporous DSR. (B) Mimics reconstruction of soft tissue stained with PMA and imaged with microCT, where the DSR is shown in blue and the quantified segment of the fibrotic capsule is shown in purple. (C) Thickness analysis in Mimics where surface shell elements are shown, and thickness is calculated as the distance between them. (D) Average thickness across fibrotic capsule as measured by Mimics. (E) Dot plot of thickness measurement per sample (animal), n = 3 to 6 per group, data are means ± SD, ***P < 0.001.

  • Fig. 5 Histological analysis of the fibrous capsule.

    (A) Relative integrated density of yellow and green fibers (signifying immature collagen) from polarized light microscopy images of the fibrous capsule in response to different treatments, with representative images shown. (B) Relative integrated density of red and orange fibers (signifying mature collagen) from polarized light microscopy images of the fibrous capsule. (C) Coherency of fibrous capsule based on polarized light microscopy. (D) Representative immunofluorescent images of capsular tissue sections stained with CD68 (red, CD68; blue, Hoechst). (E) Numerical density of CD68-stained macrophages in different treatment groups. (F) Representative immunofluorescent images of capsular tissue sections stained with αSMA [blue, DAPI (4′,6-diamidino-2-phenylindole); green, αSMA; red, CD31]. (G) Total volume of αSMA+ cells (mm3). (H) Representative images of capsular tissue sections stained with CD31. (I) Number of blood vessels per square millimeter. (J) Radial diffusion distance for regime 2 compared with control. D, device; n = 3 to 6 per group; data are means ± SD; **P < 0.01, ***P < 0.001.

  • Fig. 6 Enhanced pharmacokinetics through a porous DSR with actuation.

    (A) Timeline for in vivo studies for porous DSR. (B) Images from the IVIS at day 14 at 0, 30, and 60 min showing the implanted actuation and control groups. (C) Area under the fluorescence curve at days 8 and 14 for actuated and control groups, n = 2 to 4 per group per time point, data are means ± SD. (D) Diffusion area at days 8 and 14 for actuated and control groups, n = 3 to 4 per group per time point, data are means ± SD. (E) dP/dt max, a measure of ventricle contractility for the actuated and control DSRs in a representative animal. The vertical dashed lines show time to therapeutic effect for the control and actuated groups. (F) Average dP/dt max per cycle for the first 40 s (the time to therapeutic effect for the actuated group). Ctrl, control; Act, act; AUC, area under the curve; a.u., arbitrary units.

Supplementary Materials

  • robotics.sciencemag.org/cgi/content/full/4/33/eaax7043/DC1

    Materials and Methods

    Fig. S1. Implantable actuation system.

    Fig. S2. Nonporous DSR arrays to reduce complications associated with implantable devices.

    Fig. S3. Device manufacture procedure that involves two steps: thermoforming and heat sealing.

    Fig. S4. Test setup for force characterization and porous versus nonporous computational models.

    Fig. S5. Analytical approximation for large deflection circular plate.

    Fig. S6. Parametric study using large deflection plate analytical approximation.

    Fig. S7. In vitro assessment of the effect of actuation of nonporous DSR on myofibroblast cell line (WPMY-1).

    Fig. S8. Pre-clinical implementation of the DSRs.

    Fig. S9. The dimensional effects of submerging the device, and its constituent material in saline with different concentrations.

    Movie S1. Actuation of DSR with implantable pump.

    Movie S2. Actuation of low profile nonporous DSR.

    Movie S3. Actuation of DSR in vivo.

    References (62, 63)

  • Supplementary Materials

    The PDF file includes:

    • Materials and Methods
    • Fig. S1. Implantable actuation system.
    • Fig. S2. Nonporous DSR arrays to reduce complications associated with implantable devices.
    • Fig. S3. Device manufacture procedure that involves two steps: thermoforming and heat sealing.
    • Fig. S4. Test setup for force characterization and porous versus nonporous computational models.
    • Fig. S5. Analytical approximation for large deflection circular plate.
    • Fig. S6. Parametric study using large deflection plate analytical approximation.
    • Fig. S7. In vitro assessment of the effect of actuation of nonporous DSR on myofibroblast cell line (WPMY-1).
    • Fig. S8. Pre-clinical implementation of the DSRs.
    • Fig. S9. The dimensional effects of submerging the device, and its constituent material in saline with different concentrations.
    • Legends for movies S1 to S3
    • References (62, 63)

    Download PDF

    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.mp4 format). Actuation of DSR with implantable pump.
    • Movie S2 (.mp4 format). Actuation of low profile nonporous DSR.
    • Movie S3 (.mp4 format). Actuation of DSR in vivo.

    Files in this Data Supplement:

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