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.