Poster W15 - Sildenafil-Releasing Carbohydrate-based Hydrogel for Arteriovenous Fistula Maturation

Friday, October 25, 2024

3:30 PM – 4:30 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Shahab Edalatian Zakeri, PharmD

PhD Student
Department of Biomedical Engineering, Rowan-Virtua School of Translational Biomedical Engineering & Sciences, Henry M. Rowan College of Engineering, Glassboro, New Jersey, United States

Co-Author(s)

Sungwon Jung, Dr

Postdoctoral researcher
Wyss Institute for Biologically Inspired Engineering, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts
Somerville, Massachusetts, United States
SH

Sung-eun Heo

Graduate student
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Republic of Korea, United States
SA

Sania Aamir

Department of Biomedical Engineering, Rowan University, Glassboro, New Jersey, United States

Last Author(s)

HH

Hartej Hundal

Department of Biomedical Engineering, Rowan University, Glassboro, New Jersey, United States

Co-Author(s)

JH

Jinkee Hong

Professor
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Republic of Korea, United States

Primary Investigator(s)

PH

Patrick Hwang, PhD (he/him/his)

Assistant Professor
Department of Biomedical Engineering, Rowan-Virtua School of Translational Biomedical Engineering & Sciences, Henry M. Rowan College of Engineering, Glassboro, New Jersey
Cherry Hill, New Jersey, United States

Introduction: About 500,000 patients in the U.S. suffer from end-stage renal disease, and more than 60% of patients undergo dialysis. Arteriovenous fistulas (AVFs), created by direct anastomosis between a native artery and vein, are considered the gold standard of vascular access for dialysis. However, up to 60% of AVFs fail to mature sufficiently to allow dialysis because of inadequate vasodilation and early venous neointimal hyperplasia development. Therefore, to improve AVF maturation, we have developed a self-assembled carbohydrate-based hydrogel for sustained release of sildenafil, a phosphodiesterase-5 inhibitor, to promote blood vessel dilation and limit smooth muscle cell proliferation. The hydrogel consists of natural guar gum and gelatin polymers which are biodegradable, biocompatible, and FDA-approved. The combination of these polymers allows for tunable gelation properties and drug release kinetics.

Materials and

Methods: To improve the mechanical properties of guar gum, we modified it using sodium metaperiodate and produced guar gum with three degrees of oxidation and evaluated with TNBS assay. The sildenafil-encapsulated hydrogel was fabricated using oxidized guar gum, gelatin, and food-grade microbial transglutaminase as the gelatin cross-linker. Gel properties were characterized by rheology and injectability, and the chemical structure was evaluated by XPS and FT-IR.

Results, Conclusions, and Discussions: Hydrogels were injectable, with those containing higher levels of oxidized guar gum exhibiting a more viscous appearance. Based on rheology tests, increased oxidization level correlated with a higher storage modulus and showed a shear-thinning behavior. Structural evaluation shows Schiff’s base formation between gelatin and oxidized guar gum as well as ester bond formation between oxidized guar gum and citrate salt of sildenafil. Finally, drug release kinetics test demonstrated sustained release over 1 month (Figure 1). Our results indicate that this hydrogel has great potential to be tested in vivo on rat models of AVF, after performing safety and efficacy studies on vascular smooth muscle cells.

Acknowledgements (Optional):