Publications

Transendocardial Catheter Delivery of Artificial Biopolymer Matrices for Enhanced Cell Retention in Cardiovascular Cell Based Therapy

Didier Rouy, Aaron Miller, Daniel Rosenman, Beto Peliks, Olin Palmer, Federico Gutierez, Peter A. Altman, BioCardia Inc., August 2007, South San Francisco, CA

Background
Cardiac regeneration strategies using stem cells have repeatedly had inefficient cell retention in the target zone. Biopolymers can enhance local cell retention by two theoretical means: First, the entrapment of cells within an in-situ cross linked or gelled biopolymer matrix providing a matrix to support tissue integration. Secondly, by acting as a sealant to the lymphatic and venous drainage routes by which cells can be flushed away from the targeted delivery site. However, release of cell aggregates, cells suspended in viscous biopolymer gels, or controlled release biotherapeutic formulations within the left ventricular chamber during transendocardial delivery could cause life threatening embolic events. This safety issue has not been described or addressed previously.

Methods and Results
A new tri-lumen bipolar helical needle transendocardial catheter system has been developed which both enables the delivery of advanced biotherapeutic strategies for myocardial regeneration and repair, and presents a number of design features to address embolic safety concerns. Catheter has been built on the footprint of a Helical needle catheter currently in use in clinical trials. Commercially available two part biopolymers were run through the catheter at various flow rates and volumes in-vitro, and into swine myocardium ex-vivo. Transendocardial injection was shown to be feasable, with acceptable generated pressures. The critical issue of leakage into the ventricular chamber was assessed showing that this could be eliminated, thus addressing that this delivery system provides a means to confirm engagement to the tissue before delivery, assesses myocardial venous and lymphatic drainage at the selected delivery site prior to delivery, and inhibits back-leak of delivered agents after delivery. Theoretical considerations suggest that optimal mixing of two part biopolymers in tissue is achieved with viscosity matching.

Conclusions
Catheter based tissue matrix delivery approaches have significant potential as tools to provide broad utility for cardiovascular tissue engineering strategies. This technology is eventually meant to combine a delivery device, an engineered matrix, and cells that are being used in ongoing clinical investigations.