Available online 16 April 2024

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Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. Herein, a dual functional submicron textured nitric oxide (NO)-releasing catheter was developed. The hemocompatibility and antithrombotic activity of vascular catheters were evaluated in both 20 h in vitro blood loop and 7 d in vivo rabbit model. Surface characterization assessments via atomic force microscopy show the durability of the submicron pattern after incorporation of NO donor S-nitroso-N-acetylpenicillamine (SNAP). The SNAP-doped catheters exhibited prolonged and controlled NO release mimicking the levels released by endothelium. Fabricated catheters showed cytocompatibility when evaluated against BJ human fibroblast cell lines. After 20h in vitro evaluation of catheters in a blood loop, textured-NO catheters exhibited a 13-times reduction in surface thrombus formation compared to the control catheters, which had 83% of the total area covered by clots. After the 7 d in vivo rabbit model, analysis on the catheter surface was examined via scanning electron microscopy, where significant reduction of platelet adhesion, fibrin mesh, and thrombi can be observed on the NO-releasing textured surfaces. Moreover, compared to relative controls, a 63% reduction in the degree of thrombus formation within the jugular vein was observed. Decreased levels of fibrotic tissue decomposition on the jugular vein and reduced platelet adhesion and thrombus formation on the texture of the NO-releasing catheter surface are indications of mitigated foreign body response. This study demonstrated a biocompatible and robust dual-functioning textured NO PU catheter in limiting fouling-induced complications for longer-term blood-contacting device applications.

Statement of Significance

Catheter-induced thrombosis is a major contributor to infectious and mechanical complications of biomaterials that lead to device failure. This study demonstrated a robust, biocompatible, dual-functioning textured nitric oxide (NO) polyurethane catheter in limiting fouling-induced complications for longer-term blood-contacting device applications.

The fabricated catheters exhibited prolonged and controlled NO release that mimics endothelium levels. After the 7 d in vivo model, a significant reduction in platelet adhesion, fibrin mesh, and thrombi was observed on the NO-releasing textured catheters, along with decreased levels of fibrotic tissue decomposition on the jugular vein. Results illustrate that NO-textured catheter surface mitigates foreign body response.

Section snippetsINTRODUCTION

Intravascular catheter insertion is common in hospitals and outpatient settings for various purposes, such as administering fluids, medication, blood, and nutrients. However, venous access through catheterization often induces blood clot formation. Implanted catheters rapidly acquire layers of fibronectin and fibrin upon insertion, accelerating the surface deposition and accumulation of foulants. It is estimated that nearly 18% of central venous catheter insertion can lead to thrombotic

MATERIALS

The solid thermoplastic silicone polycarbonate polyurethane (PU) Carbosil® 20 80A was kindly provided by DSM Biomedical Inc (Exton, PA, USA) and was used for the fabrication of textured and smooth films and catheters. PU pellets were dissolved in N,N-dimethylacetamide (DMAC, BDH. chemicals), and three concentrations of polymers (∼12, ∼18 and ∼40 w/v%) were prepared. SNAP was purchased from PharmaBlock (Hatfield, PA, USA) and dissolved in the ∼18 w/v% Carbosil 20 80A PU solution to yield a 20%

Surface Properties of Textured PU Films

Smooth and textured PU films were first fabricated by a soft lithography two-stage replication process to fabricate the SNAP-doped PU catheters. In a prior study, we developed “sandwich-like” polymer films with a textured pattern in the top layer, the SNAP-doped PU in the middle layer, and regular PU in the base layer [19]. The top and base layers of PU in the “sandwich-like” structure films separate the direct interactions of SNAP and fluid, potentially extending the NO release lifetime and

CONCLUSION

The experimental work presented here provides one of the first investigations into the hemocompatibility of textured topography under a long-term in vivo model. Previous in vivo models have explored the effect of microtextured surfaces on only percutaneous devices [43]. Much uncertainty still exists about the in vivo efficacy of textured topography in a blood-contacting environment. In this study, we reported the development of submicron-textured NO-releasing catheters and assessed the

CRediT authorship contribution statement

Yi Wu: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing. Li-Chong Xu: Conceptualization, Data curation, Formal analysis, Investigation, Writing – original draft, Writing – review & editing. Eric Yeager: Formal analysis, Investigation, Writing – review & editing. Keren Gabriela Beita: . Natalie Crutchfield: Formal analysis, Investigation, Writing – review & editing. Sarah N. Wilson: . Patrick Maffe: Formal

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

Dr. Hitesh Handa is a founder of Nytricx INC, which is involved in exploring possibilities of using nitric oxide-releasing materials for medical applications.

ACKNOWLEDGEMENTS

The authors acknowledge financial support from the National Institutes of Health (NIH) grants R01HL153231 and R01HL134899. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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