Methods:
Animal ModelA subcutaneous implantation study was designed in New Zealand White (NZW) rabbits using dorsal bilateral surgeries to implant CIEDs with or without supportive CanGaroo ECM Envelopes. The New Zealand White rabbit was chosen because it provided enough surface area on the dorsal surface for implantation of the test and control articles of a clinically relevant size (pacemakers approximately 5.5 x 5.5 x 0.5 cm). The rabbit is an appropriate subcutaneous pre-clinical model for evaluating biocompatibility and local effects of implanted materials according to the current ISO testing standards (ISO 10993-6) because of their competent immune system and skin thickness similar to that of humans, as opposed to other small animal models such as rats and mice.
Study DesignThe study protocol was approved by the Institutional Animal Care and Use Committee (IACUC) and all animals received humane care in compliance with “The Guide for the Care and Use of Laboratory Animals,” published by the US National Institutes of Health. Twenty one (21) NZW rabbits were implanted with CIEDs with eleven being placed in CanGaroo ECM Envelopes. Midline incisions were created on the dorsal lumbar aspect of each animal, per veterinary practice. Subcutaneous pockets were created with minimal pocket dissection and just large enough to accommodate one implant per pocket.
For the experimental group, eleven single-chamber pacemakers (St. Jude Medical) without leads were placed in CanGaroo Envelopes (Size Medium, Aziyo Biologics, Lot# M17E1116) (Figure 1) . The pacemaker lead header was oriented nearest to the opening in the hydrated envelope, and the lead header was placed in the implant pocket closest to the skin incision. The envelope-CIED assembly was secured with a single, non-absorbable suture (3-0 Prolene) that passed across the envelope opening edges in order to prevent incidental release of the CIED and secured to the underlying chest wall. A second non-absorbable suture was passed through the chest wall, envelope, and pacemaker header suture hole to secure the implant. For the control group, ten CIEDs without envelopes were again oriented with the lead header closest to the skin incision and secured in place through the suture hole with a single, non-absorbable suture. The pocket surrounding each implant was closed to contain the implant using a continuous stitch and non-absorbable suture to reconnect the subcutaneous tissues around each implant. From there, standard surgical techniques were used to finish closing the implant sites.