Infection is a serious and potentially fatal complication of surgery to deliver cardiovascular implantable electronic devices (CIEDs) (i.e., pacemakers and implantable cardioverter-defibrillators). Untreated device-related infection is associated with mortality rates as high as 66%. Currently, only one antibiotic-impregnated mesh has been FDA-approved for placement in surgical incisions to reduce infections associated with the implantation of CIEDs. However, staphylococci bacteria, which are commonly found in CIED infections, have well documented resistance to the combination antibiotics used in the mesh. Moreover, the antibacterials can promote the growth of fungii ? a source of rare, but highly fatal CIED infections. The use of the current, bulky implantable mesh envelops increase surgical pocket size, which can restrict a patient's physical activities and increase the chance of infection. And the mesh, itself, contributes to the space constraints of the surgical pocket, which reduces the size of the CEIDs that can be accommodated; yet the vast majority of patients would prefer larger devices that last longer. Increasing the length of time between device retrievals and reimplantations would improve the quality of life for patients while decreasing the risk of infections associated with surgery. The objective of this Phase I SBIR proposal is to use 3D printing to fabricate a biodegradable polycaprolactone (PCL)-based antimicrobial envelope, to be fitted outside of cardiac rhythm devices, which will prevent infections after surgical implantation. The hypothesis is that a slow degradation (hydrolysis) of the PCL envelope will gradually release a novel antimicrobial compound (CSA-131, a ceragenin) for antimicrobial and anti-fungal activity. CSA-131 is a synthetic non-peptide compound, with no pre-existing pool of resistance, that mimics the activity of the body's endogenous antimicrobial peptides. The proposed device will be the first to prevent fungal colonization of cardiac devices, while still providing superior and longer lasting inhibition of bacterial growth. Moreover, the customization allowed by 3D printing will also minimize surgical pocket space constraints. To advance this antibiotic mesh technology, a PCL filament for 3D printing applications will be developed that is loaded with the antimicrobial, CSA-131. The elution profiles of the filament will be evaluated and the in vitro efficacy of CSA-131 will be tested. Next, envelopes composed of antibiotic-loaded filament will be fabricated (3D printing), following a design that accommodates a pacemaker. And, finally, the antimicrobial and anti-fungal properties of the PCL envelope will be demonstrated and its cytotoxicity evaluated. It is expected that incorporation of CSA-131 into a 3D printed biodegradable mesh will either prevent or significantly reduce biofilm formation on CIEDs when exposed to daily inocula of Staphylococcus aureus (MRSA) for at least 60 days. This project will pioneer the melding of a novel antimicrobial with a 3D printing, PCL filament, thereby enabling the production of custom-fit envelops for pacemakers and facilitating trouble free surgical implantation. 1

Public Health Relevance

Through the development of an antimicrobial envelope for cardiovascular implantable electronic devices (CIEDs), i.e., pacemakers and implantable cardioverter-defibrillators, Saranas will greatly reduce the incidence of infections associated with the implants. Reducing the number of CIED-related infections will also greatly reduce the cost-of-care for these patients, which increase by $50,000 per patient when an infection is acquired.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Small Business Technology Transfer (STTR) Grants - Phase I (R41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lee, Albert
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
N8 Medical, Inc.
United States
Zip Code