Injectable hydrogel electrodes as conduction highways to restore native pacing

Figures

• 

  Fig. 1. Design of injectable hydrogel electrode. Redox initiation reaction of polyether urethane diacrylamide (PEUDAm) macromer + N-acryloyl glycinamide (NAGA) delivered using double barrel syringe with a mixing head. Ammonium persulfate (APS) and iron gluconate (IG) are used as initiator and reducing agents. Resulting hydrogels display bidentate hydrogen bonding at netpoints for improved durability. Ionic conductivity is conferred through the inclusion of salt species in the hydrogel precursor solution.

• 

  Fig. 2. In vivo assessment of injectable electrode in coronary vein of a porcine model. A Postmortem confirmation of in situ cure of hydrogel in the anterior interventricular vein (AIV) (H1) and tributaries (H2). Coronary vein image from IMAIOS.com. B Injected hydrogel homogeneity assessment of gel fraction (pink circles) and swelling ratio (green circles). Means and standard deviation are presented (n = 3 independent animals, 5 hydrogel segments per animal). ns = nonstatistical difference between the segments (p > 0.05) determined with an ordinary two-way ANOVA. For multiple comparisons, a Tukey’s test with a single pooled variance was used. Source data are provided as a Source Data file. Exact p-values were provided in the source data file. C Host response after 4 weeks (P-2165, Animal AIV 2) implantation using slices of the location proximal to the injection site, middle of the vein, and the control from an alternate section of the anterior left ventricle (LV) wall. The response includes damage induced at the hydrogel injection site, with 1) Arrows are presented in the images on the Supplementary information with foreign body giant cell reaction). Mid branch of the hydrogel injection…

• 

  Fig. 3. Schematic of injectable hydrogel system to transform coronary veins into flexible electrodes that capture inaccessible cardiac tissue. A Hydrogel precursors solutions are delivered using a dual lumen catheter to fill coronary veins and tributaries that span the myocardium near the scarred tissue. Upon mixing of the two hydrogel solutions in the coronary veins, redox-initiated crosslinking results in rapid cure of the ionic hydrogel. B Subsequent connection to a pacemaker lead to the ionic hydrogel electrode provides increased tissue contact across the myocardium. C Wavefront activation of the myocardium along the hydrogel electrode reduces the energy required for defibrillation. D Lead I of surface ECG showing electrical activation at baseline (sinus rhythm) and when paced. Peak of the baseline QRS morphology was matched with the peak of QRS morphology obtained from pacing with hydrogel in AIV (Top, left to right) Baseline: Activation during sinus rhythm starts from the sinoatrial node and travels through the atrioventricular node into the Purkinje fibers in the ventricles. Pacing the myocardium directly causes the QRS morphology to invert indicative of deviation from normal…

• 

  Fig. 4. Cardiac electroanatomical mapping studies in a porcine ablation model. A Image of cardiac ablation near the AIV with substantial depth of the ablation lesion formation. B Endocardial electroanatomical mapping of point pacing before and after ablation with red indicating early capture and blue indicating late capture. Point pacing location is indicated by a small white circle and region of lesion by dotted black line. Illustration demonstrating how point pacing allows for development of re-entrant circuits (indicated by the orange arrows) due to heterogenous capture and activation around the lesion (brown area). C Endocardial electroanatomical mapping of hydrogel pacing after ablation with red indicating early capture and blue indicating late capture. Hydrogel electrode location is indicated by a blue line and region of lesion by dotted black line. Illustration demonstrating how the hydrogel in the vein generates a planar wavefront through long, linear areas of capture that prevent re-entry by normalizing conduction across heterogenous tissue. Scale represents the tissue activation time from 0 to 150 ms after pacing.