Evaluation of the Bioinductive Effects of a Novel Antibiotic Eluting Cardiac Implantable Electronic Device Envelope

Figures

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  Figure 1. Antibiotic-eluting CIED bioenvelope pouch. The envelope is made of sheets of decellularized, non-crosslinked porcine small intestine submucosa extracellular matrix (SIS-ECM; as labelled) with perforation holes (black dots). The envelope holds an internalized bioabsorbable polymer disc containing the antibiotics rifampin and minocycline. Polymer disc is labelled as Antibiotic-Eluting Bioabsorbable Polymer Disc and highlighted by white line.

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  Figure 2. Eluted biofactors from the CIED envelopes and fibroblasts after 24 h. (A) Mouse 3T3 fibroblasts were seeded on tissue culture plastic with or without SIS-ECM and incubated for 24 h to generate conditioned media for multiplex analysis. (B) Inflammatory and (C) angiogenic protein concentrations were measured by the multiplex analysis of the 3T3 cultured media. Plastic served as the control (n = 6, biological replicates) and was compared with SIS-ECM (n = 6, biological replicates). GCSF, granulocyte stimulating factor; IL6, interleukin 6; KC, keratinocyte chemoattractant; MCP1, monocyte chemoattractant protein 1; VEGF-A, vasculogenic endothelial growth factor A; HGF, hepatocyte growth factors; FGF2, fibroblast growth factor 2; SDF-1, stromal cell-derived factor 1. Data are presented as the mean ± SD. ** p < 0.01, **** p < 0.0001 (two-tail, Student’s T-test).

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  Figure 3. Bioactive factors eluted from the 7-day biopsy explants post 24 h incubation. (A) Four dorsal subcutaneous pockets were created in mice and randomly assigned implantation with no biomaterial (sham) or SIS-ECM. Biopsy of the skin and implant was then removed at 7-days and incubated for 24-h to generate conditioned media for multiplex analysis. (B–N). Sham media served as the control (n = 4–8, biological replicates) and were compared with SIS-ECM (n = 4–8, biological replicates). Data are the presented as mean ± SD. Abbreviations as in Figure 2. * p < 0.05, ** p < 0.01, **** p < 0.0001 (two-tail, Student’s T-test).

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  Figure 4. Graphical representation of the long-term healing study with rabbits. (A) Rabbits were randomly assigned with HDPE or SIS-ECM subcutaneous implantation and sacrificed at specified time points (2, 10, and 26 weeks) for histological analysis. (B) Sample images of hematoxylin and eosin-stained histological sections of tissue explants with either HDPE or SIS-ECM that were used for analysis and scoring. Asterisks (*) represent the HDPE control and the arrows mark SIS-ECM.

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  Figure 5. Microscopic scores of inflammation and tissue response of the histological sections of rabbit dorsal subcutaneous tissue at 2, 10, and 26 weeks. (A) Rabbits were randomly subjected to either high-density polyethylene (HDPE) or SIS-ECM in one of the four dorsal subcutaneous pockets. Inflammation, neovascularization, fibrosis score, and fibrotic capsule thickness around the HDPE (n = 7–12 biological replicates) and SIS-ECM (n = 8–11 biological replicates) were measured at week 2 (A) and subsequent measures for the week 10 (B) and week 26 explants (C). Data are presented as the mean ± SD. * p < 0.05, ** p < 0.01, *** p < 0.001 **** p < 0.0001 (two-tail, Student’s T-test).