Poster B9 - An Antimicrobial Self Assembling Peptide Hydrogel for Vascular Graft Infection

Thursday, October 24, 2024

10:00 AM – 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

SP

Siya Patel

Undergraduate Student
New Jersey Institute of Technology, United States

Co-Author(s)

Abhishek Roy, BS

PhD Student
New Jersey Institute of Technology
Newark, New Jersey, United States
Gelavizh Gharati (she/her/hers)

PhD Student
New Jersey Institute of Technology
Harrison, New Jersey, United States
Αlexandra Griffith

PhD Candidate
New Jersey Institute of Technology
Waldwick, New Jersey, United States
CH

Corey Heffernan, PhD

Res Asst Prof
NJIT
Newark, New Jersey, United States
KS

Karim Salem, MD

Assistant Professor
Rutgers New Jersey Medical School
Newark, New Jersey, United States

Primary Investigator(s)

Vivek Kumar, PhD

Associate Professor
New Jersey Institute of Technology
Newark, New Jersey, United States

Introduction: Vascular graft infection (VGI) can lead to sepsis, amputation of the correlated region [1] and is correlated with high morbidity and mortality. Current treatment for VGI is surgery from which a large percentage of patients develop perioperative and postoperative complications and infections [2]. Therefore, there is an unmet need for an implantable vascular graft that is resistant to current or future infection. The objective of this study is to validate the broad-spectrum antimicrobial properties and biocompatibility of a self-assembling peptide hydrogel (SAPH) for the treatment of vascular graft infection.

Materials and

Methods: The peptide was prepared in a Liberty Blue Solid Phase peptide synthesizer utilizing Fmoc chemistry. The lyophilized peptide was formulated in PBS and dissolved at various concentrations. The various concentrations of the SAPH were injected into the subcutaneous space of a healthy rodent. The biocompatibility of the SAPH was determined at the end of a 28 day study. In the subcutaneous implantation in vivo study, ePTFE, Dacron, and Teflon vascular grafts will be inoculated with S. aureus and implanted in the subcutaneous region. The SAPH is injected subcutaneously in the area of the implantation and compared to a PBS control. In the intraperitoneal implantation in vivo study, ePTFE, Dacron, and Teflon vascular grafts will be similarly inoculated with S. aureus but implanted in the intraperitoneal space. Both studies will be performed for 3, 7, 14, and 28 days. At the end of the study, the pertinent tissue will be collected from the animals and bacteria will be quantified by Colony-Forming Unit (CFU) counting.

Results, Conclusions, and Discussions: We have validated the antimicrobial efficacy of our SAPH peptide in numerous in vitro and in vivo assays. For example, our SAPH has broad spectrum efficacy against numerous other pathogenic bacteria (both Gram positive and negative, anaerobic and aerobic) as well as fungi in vitro, including against preformed biofilms of bacteria and fungi. For in vivo biocompatibility, our SAPH was injected in the subcutaneous region in rodents at various concentrations (1 mM, 3 mM, 4 mM, 6 mM, and 8 mM) and tissue collected at 28 days. The excised tissue was stained with H&E and Trichrome and analyzed for cell density within the region and blood vessel formation and confirmed the biocompatibility of the SAPH (Figure 1B).

The broad spectrum antimicrobial properties and in vivo biocompatibility strongly suggests that our SAPH technology hold great promise in treating vascular grafts and treating/guarding against infection. Future studies will evaluate and optimize the formulation of the hydrogel for a robust and long term response in a diseased model and translating them for clinical trial use. We will also conduct an in vivo study by implanting the inoculated vascular grafts in the intraperitoneal space to treat implants with the antimicrobial SAPH.

Acknowledgements (Optional): 1. Hussam Tabaja, Supavit Chesdachai, Aditya S Shah, Ryan W Stevens, Randall R DeMartino, Young M Erben, Walter R Wilson, Larry M Baddour, Daniel C DeSimone, Fostering Collaborative Teamwork—A Comprehensive Approach to Vascular Graft Infection Following Arterial Reconstructive Surgery, Clinical Infectious Diseases, (2024).

2. Marjan Wouthuyzen-Bakker, Marleen van Oosten, Wouter Bierman, Rik Winter, Andor Glaudemans, Riemer Slart, Marlous Toren-Wielema, Ignace Tielliu, Clark J. Zeebregts, Niek H.J. Prakken, Jean Paul de Vries, Ben R. Saleem, Diagnosis and treatment of vascular graft and endograft infections: a structured clinical approach, International Journal of Infectious Diseases, Volume 126, 2023, Pages 22-27, ISSN 1201-9712, https://doi.org/10.1016/j.ijid.2022.11.011. (https://www.sciencedirect.com/science/article/pii/S120197122200594X)