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A Biocompatible Nanofibrous Coating Of Prosthetic Vascular Grafts As A Drug Delivery System For The Treatment Of Vascular Graft Infections
Stefano Serpelloni,
Vy C. Dang, Shashank Sharma, MD, Francesca Taraballi, PhD, Maham Rahimi, MD, PhD.
Houston Methodist Hospital, Houston, TX, USA.
OBJECTIVES: More than 400,000 vascular grafts are implanted annually in USA, and vascular graft infection (VGI) is a major complication that affects 1-6% of the cases. VGI is a serious complication with significant morbidity, mortality, and healthcare costs. The available treatments rely on administration of systemic antibiotics and debridement of the surgical wound. If not properly addressed, bacterial infiltration can lead to graft removal, major soft tissue defects, sepsis and eventually death. Here, we describe a chitosan-based nanofibrous coating (CNC), a reservoir for drug delivery and an effective agent against fungus and Gram-negative and positive bacteria. The coating can be loaded with different concentrations of antibiotics and applied to vascular grafts as a novel approach against VGI.
METHODS: The CNC was performed using the electrospinning technique. Four different formulations were evaluated using different concentrations of poly(vinyl alcohol) (PVA) and poly(ethylene oxide) (PEO) and two different concentrations of vancomycin (low and high content) as the antimicrobial agent. A poly(lactic-co-glycolic acid) (PLGA) layer was applied via electrospinning on top of the nanofibrous layer to slow down release kinetics. The resulting CNC was characterized using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA). Vancomycin content was directly quantified with High Pressure Liquid Chromatography (HPLC). CNC biocompatibility was assessed after seeding human umbilical vein endothelial cells (hUVEC) onto the nanofibrous mat.
RESULTS: The analysis of SEM images showed a homogeneous deposition of nanofibers in both PVA- and PEO-based formulations with diameters ranging from 205 ± 70 nm (mean ± SD) and 173 ± 55 nm respectively. FTIR and TGA assessment demonstrated the characteristic peak of vancomycin, confirming its presence in the final CNC. HPLC analysis showed a sustained release of vancomycin for up to 7 days. hUVECs were viable and spread across the nanofibrous mat 24 h after seeding, demonstrating high biocompatibility of the construct.
CONCLUSIONS: In our ongoing studies, we aim to develop a novel, biodegradable CNC of vascular prosthetics that facilitates a local and sustained delivery of vancomycin to prevent VGIs. These preliminary results highlight the project feasibility through the techniques described above. Future studies will include evaluation of release dynamics and vancomycin encapsulation within the CNC. This data should provide an exciting pre-clinical proof-of-concept and strong scientific foundation towards further clinical development.
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