Research ArticleMATERIALS SCIENCE

Light-degradable hydrogels as dynamic triggers for gastrointestinal applications

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Science Advances  17 Jan 2020:
Vol. 6, no. 3, eaay0065
DOI: 10.1126/sciadv.aay0065
  • Fig. 1 Light-degradable hydrogel synthesis scheme.

    (A) Schematic of light-degradable 3D hydrogel network. (B) Custom-synthesized acrylated oNB linker. (C) Schematic of linker integrating with any polymer network that relies on acrylate-based radical polymerization.

  • Fig. 2 Mechanical and biocompatibility characterization of light-degradable hydrogels.

    (A) Light-degradable single- and double-network hydrogels can be synthesized from an array of biocompatible polymer backbones with acrylate functional groups, such as PAMPS and PAAM. (B) Mechanical properties of PAMPS, PAAM, and PAMPS/PAAM hydrogels with MBAA and oNB light-degradable linkers showing significant increases in mechanical properties in double-network hydrogels, as compared to single-network hydrogels (n = 3, P < 0.05). Results reported are for 1 M PAMPS with 4 mol % cross-linker (MBAA or oNB) and 2 M PAAM with 0.1 mol % cross-linker (MBAA or oNB). (C) In vitro toxicity study on two cell lines (HT29 and Caco-2) of PAAM network synthesized with light-degradable oNB linkers compared to negative control (− Control, untreated cells) and positive control (+ Control, cells treated with methanol). No significant negative effect of custom-synthesized light-degradable linker is observed (n = 4, P < 0.05).

  • Fig. 3 Tunable degradation of light-triggerable hydrogel.

    (A) Light intensity drops as a function of distance from the light source and the number of LEDs (365 nm). Inset: Schematic of array placement over light meter sensor. (B) Degradation of oNB-PAAM (4 M PAAM with 0.1 mol % oNB cross-linker) as a function of exposure time and distance from the three-LED array 365-nm light source (n = 3). (C) Effect of changing the percentage of oNB linker on ultraviolet (UV) light responsiveness of 4 M PAAM gels. Increasing the percentage of oNB linker leads to more significant drops in mechanical properties after 45-min degradation at 365 nm (n = 3, P < 0.05). (D) Effect of changing light wavelength from 365 to 405 nm. Shorter wavelengths lead to more significant drops in mechanical properties of 4 M PAAM gels with 0.1 mol % oNB cross-linker after 45-min degradation (n = 3, P < 0.05). (E) In vitro toxicity study on two cell lines (HT29 and Caco-2) of oNB-PAAM gels after degradation compared to negative control (− Control, untreated cells) and positive control (+ Control, cells treated with methanol), showing no significant effect of degradation by-products on cell viability (n = 4, P < 0.05).

  • Fig. 4 Light-degradable hydrogels as dynamic triggers in GI devices.

    (A) Schematic of balloon insertion and inflation (left), degradation via either an endoscopic or untethered LED light source (middle), and subsequent deflation (right). (B) Casting of oNB-PAAM gel pins (top) and assembled balloon sealed with a cast gel pin (bottom). Photo credit: Ritu Raman, MIT. (C) Balloon is inserted through the esophagus and swells in the stomach as observed endoscopically 1 min after insertion (top) and radiographically (bottom) immediately after insertion and after 6 hours in vivo. (D) Design of LED cap that can be attached to the inserted end of an endoscope. Wires to power the LEDs are threaded through the endoscope, and a hole in the array maintains visibility through the endoscope’s integrated camera. A magnet at the center of the array enables docking to the metallic piece attached to the sealed end of the balloon. (E) Design of ingestible pill-shaped LED. Computer-aided design (CAD) rendering shows assembly process for ingestible LED: Batteries, LED, and magnet are inserted into 3D-printed hollow cylindrical body and sealed with epoxy into a water-tight device. LED is turned on when a metal conductive tab is pushed into the slit in the side of the device. Magnetic docking of the LED to the balloon in vivo is observed radiographically (bottom right). (F) After the light-triggerable oNB-PAAM gel pin is degraded, the filler leaks out and the balloon decreases significantly in size as observed radiographically at t = 0 hours (top) and 6 hours (bottom). (G) The balloons degraded using both the endoscopic LED array and untethered LED decreased significantly in size at t = 6 hours as compared to a control (n = 3, P < 0.05), indicating successful on-demand activation of the oNB-PAAM gel trigger. (H) Schematic of esophageal stent device composed of an oNB-PAMPS gel ring with PCL beads. (I) Photograph (top) and radiographic image (bottom) of the assembled device. PCL beads are painted with a barium sulfate paint to increase visibility via x-ray. Photo credit: Ritu Raman, MIT. (J) The assembled device is placed inside an ex vivo esophagus, and swelling of the device ensures a press fit with the tissue that withstands compression. (K) Reduction in the esophageal stents’ resistive force to external compression in vitro and ex vivo after light-triggered degradation (n = 3, P < 0.05). (L) Top: Following degradation with the endoscopic LED array described in (D), the gel changes color from clear to orange, an indicator of degradation as observed in fig. S6. Bottom: The degraded gel leaks out of the esophagus when the tissue is compressed to half its original width commensurate with esophageal peristaltic movement in vivo. Photo credit: Ritu Raman, MIT.

Supplementary Materials

  • Supplementary material for this article is available at http://advances.sciencemag.org/cgi/content/full/6/3/eaay0065/DC1

    Fig. S1. Schematic and characterization of light-triggerable linker.

    Fig. S2. Mechanical and biocompatibility characterization of tough hydrogel platform.

    Fig. S3. Characterization of light-induced hydrogel degradation in vitro.

    Fig. S4. Synthesis of gastric-resident balloon sealed with light-degradable hydrogel.

    Fig. S5. In vitro characterization of gastric-resident balloon swelling.

    Fig. S6. In vitro mechanical characterization of gastric-resident balloon before and after degradation.

    Fig. S7. Custom-manufactured light-emitting devices for in vivo triggering of light-degradable hydrogels.

    Fig. S8. Synthesis and characterization of light-triggerable esophageal stent.

    Movie S1. Balloon swelling in gastric environment in vivo.

    Movie S2. Endoscopic LED cap turning on in vivo.

    Movie S3. Demonstration of ingestible LED tethering to balloon in vivo.

  • Supplementary Materials

    The PDFset includes:

    • Fig. S1. Schematic and characterization of light-triggerable linker.
    • Fig. S2. Mechanical and biocompatibility characterization of tough hydrogel platform.
    • Fig. S3. Characterization of light-induced hydrogel degradation in vitro.
    • Fig. S4. Synthesis of gastric-resident balloon sealed with light-degradable hydrogel.
    • Fig. S5. In vitro characterization of gastric-resident balloon swelling.
    • Fig. S6. In vitro mechanical characterization of gastric-resident balloon before and after degradation.
    • Fig. S7. Custom-manufactured light-emitting devices for in vivo triggering of light-degradable hydrogels.
    • Fig. S8. Synthesis and characterization of light-triggerable esophageal stent.

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    Other Supplementary Material for this manuscript includes the following:

    • Movie S1 (.mov format). Balloon swelling in gastric environment in vivo.
    • Movie S2 (.avi format). Ferrofluid filled into a long S-RuM architecture.
    • Movie S3 (.avi format). Demonstration of ingestible LED tethering to balloon in vivo.

    Files in this Data Supplement:

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