CARD29: An Acellular Biologic Extracellular Matrix (ECM) Envelope for Cardiovascular Implantable Electronic Devices: Preclinical Evaluation

Abstract

Background: Cardiovascular implantable electronic device (CIED) implant sites usually heal with hypovascular fibrotic capsule formation which can lead to complications including device movement, infection risk and reoperative challenges. An ECM CIED envelope at implant may promote stabilization, constructive tissue remodeling, reduced fibrosis and increased vascularity. Methods: Ten rabbits received single-chamber pacemakers (PMs) (St. Jude Medical) in ECM envelopes (CanGaroo® Envelope, Aziyo Biologics, Silver Spring, MD) and 10 received identical PMs without envelopes. One PM+ECM animal was evaluated at week 2, and remaining animals were evaluated at either week 13 or 26. Implant site tissues were analyzed by gross observation and histopathology. Results: PM+ECM animals had a 5-fold reduction in PM subcutaneous movement (migration or device flipping) compared to the PM only group. Histology showed progressive ECM envelope resorption by 13 and 26 weeks, with increased vascularization over time compared to PM only group at 13 and 26 weeks (Fig 1). PM+ECM animals had a lower average capsule thickness compared to PM only group - mean of 349 ± 165µm (mean ± SD) versus 417 ± 152µm at 13 weeks and a mean of 427 ± 141µm versus 439 ± 91µm at 26 weeks. Neovascularization score (blinded pathologist, 0-4 point scale) demonstrated a significantly higher PM+ECM group average score vs. PM only (2.1 vs 1.7, p<.05, Student’s t-test). Conclusion: Porcine small intestinal submucosa ECM envelopes promoted PM implant stabilization with implant site healing remarkable for reduced capsule thickness and increased vascularity, compared to PMs without envelopes in a preclinical model. ECM envelopes may provide meaningful clinical benefits for CIED implant pockets and warrant further investigation. Figure 1: Representative gross images of the subcutaneous pocket. 1A) Images demonstrating remodeling of the ECM envelope over time at 2, 13, and 26 weeks with increasing levels of vascularization. 1B) Comparison images from PMs without envelope implant at 13 and 26 weeks show lower vascularization levels and a flipped device at 26 weeks.