What Is Endexo® Technology and How Does It Work?

The CerebroFlo® EVD catheter is indicated for temporary insertion into a ventricular cavity of the brain for external drainage of cerebrospinal fluid in those patients with elevated intracranial pressure, intraventricular hemorrhage or hydrocephalic shunt infections.

It is the only external ventricular drainage catheter with Endexo® Technology, a permanent additive that provides functionality to all surfaces as well as cut perforations. This allows for a great reduction in fibrinogen and platelet activation and adhesion, which results in less thrombus formation.* ^{4-5 ,11}

In fact, the CerebroFlo EVD catheter has shown an average of 99% less thrombus accumulation on its surface in vitro than another market-leading EVD catheter.†

The Science Behind the Molecule

The polymer backbone of the Endexo® molecule is integrated into the base polymer matrix, anchoring Endexo® molecules to the structure of the catheter material and modifying the surface properties. The fluorinated end groups functionalize all extruded and cut catheter surfaces,^{1-3, i} which results in a biologically passivated surface. This surface reduces protein adsorption,^{1,4, ii} platelet adhesion⁴ and platelet activation.⁵

When catheters are inserted into the body, biological components such as proteins can adsorb onto the catheter’s surface.⁶ The adsorbed protein layer further mediates the body’s biological response to the implanted material, promoting biomatter buildup that can occlude catheters.

Many polymers used in medical devices have surface characteristics that may adsorb proteins, activate platelets and promote conditions leading to thrombosis⁷ and foreign body reactions.⁸

The Endexo® molecule, however, is a fluorinated polymer, consisting of a polyurethane backbone and fluorinated end groups. A small amount of Endexo® molecules are blended with the CerebroFlo catheter’s base material and migrate to the catheter’s surface. At the surface, the Endexo® molecules’ polyurethane backbone remains integrated in the base matrix, while the fluorinated end groups are expressed at the catheter’s surface.

The Endexo®-modified surfaces passivate the CerebroFlo catheter to reduce adhesion of biological components. The weak intermolecular forces between the fluorinated end groups and biomatter [9, 10] allow proteins and platelets that may adhere to have less conformational change or activation, leading to less thrombosis.

The Origins of Endexo® Technology

In the video, “The Endexo Story” by AngioDynamics, Dr. Paul Santerre, a professor at the University of Toronto, recalls that he got some of the initial ideas for the creation of Endexo® from the implantation of the world’s first total artificial heart program in 1983.

The recipient of the artificial heart was a dentist who after two years began having a lot of complications associated with protein interactions with the polymers, clotting, and infections that occurred as a result of biofilm formation.

During his PhD program, Dr. Santerre studied what causes blood clots on foreign surfaces and what key proteins are involved. He sought to understand how changing chemistries can influence blood clots and how one could build an anticoagulant character directly into a device.

With this in mind, Endexo® fluorinated surface modifying macromolecules were created with three functional blocks: two fluorocarbon terminals and a central block that is compatible with the base polymer.

“You’re literally programming the polymer to be surface-modified before you even conceive making the actual product,” Dr. Santerre explains. “Endexo is the layman’s language for the scientific term ‘surface-modifying macromolecules.’”

When Plastics and Proteins Meet

Protein molecules in the human body are complex and have a unique shape. This shape, or conformation, presents specific chemical groups which determine the protein’s function and interaction with other proteins. For example, changes in the shape of various clotting proteins found in blood activates the clotting cascade.

Unfortunately, most catheters are composed of chemistries that promote protein shape changes, which in turn will lead to a presentation of chemical groups in the proteins that can activate clotting.

Endexo® macromolecules, however, modify the catheter’s surface chemistry to allow the proteins in the blood to interact with the substrate without having to change their structure, because everything they need to interact with their own structure is on the polymer.

“As soon as you stick a plastic in the body, within fractions of seconds, proteins will bond. It’s unavoidable. And that layer of proteins defines everything that’s going to happen subsequently,” he says. “When the cells start acting, the platelets start interacting, the bacteria start interacting…control that interaction and you control a lot of the phenomenon that will subsequently happen.”

* In-vitro testing. Correlation between in-vitro studies and clinical performance has not been established. Clinical results may vary.

† Based on radiolabeled platelet count. Study protocol and results on file, 1401368-1-EN.

Codman, CerebroFlo, Integra, and the Integra Logo are registered trademarks of Integra LifeSciences Corporation or its subsidiaries in the United States and/or other countries. Endexo is a registered trademark of Evonik Canada Inc. in the United States and/or other countries. ©2020 Integra LifeSciences Corporation. All rights reserved.

References

1. Tang YW, Santerre JP, Labow RS, Taylor DG. Use of surface-modifying macromolecules to enhance the biostability of segmented polyurethanes. J Biomed Mater Res. 1997;35(3):371-381.
2. McCloskey CB, Yip CM, Santerre JP. Effect of fluorinated surface-modifying macromolecules on the molecular surface structure of a polyether poly(urethane urea). Macromolecules. 2002;35(3):924-933.
3. Ho JY, Matsuura T, Santerre JP. The effect of fluorinated surface modifying macromolecules on the surface morphology of polyethersulfone membranes. J Biomater Sci Polym Ed. 2000;11(10):1085-1104.
4. Jahangir AR, McClung WG, Cornelius RM, McCloskey CB, Brash JL, Santerre JP. Fluorinated surface-modifying macromolecules: modulating adhesive protein and platelet interactions on a polyether-urethane. J Biomed Mater Res. 2002;60(1):135-147.
5. Massa TM, Yang ML, Ho JY, Brash JL, Santerre JP. Fibrinogen surface distribution correlates to platelet adhesion pattern on fluorinated surface-modified polyetherurethane. Biomaterials. 2005;26(35):7367-7376.
6. Schmidt DR, Waldeck H, Kao J. Protein adsorption to biomaterials. In: Biological Interactions on Materials Surfaces. New York: Springer; 2009:1-18.
7. Xu LC, Bauer JW, Siedlecki CA. Proteins, platelets, and blood coagulation at biomaterial interfaces. Colloids Surf B Biointerfaces. 2014;124:49-68.
8. Hu WJ, Eaton JW, Ugarova TP, Tang L. Molecular basis of biomaterial-mediated foreign body reactions. Blood. 2001;98(4):1231- 1238.
9. Dalvi VH, Rossky PJ. Molecular origins of fluorocarbon hydrophobicity. PNAS. 2010;107(31):13603-13607.
10. Krafft MP, Riess JG. Perfluorocarbons: Life sciences and biomedical uses dedicated to the memory of Professor Guy Ourisson, a true renaissance man. J Polym Sci. 2007;45(7):1185-1376.
11. Lopez-Donaire ML and Santerre JP, “Surface modifying oligomers used to functionalize polymeric surfaces: Consideration of blood contact application,” Journal of Applied Polymer Science, vol. 131, no. 14, Art. no. 14, 2014, doi: 10.1002/app.40328.

i. Arkis X-ray Photon Spectroscopy (XPS) analysis of CerebroFlo EVD Catheters demonstrated fluorinated end groups present at extruded and cut catheter surfaces.

ii. Arkis Albumin deposition study, December 2016. The study showed a 58% reduction in the adsorption of albumin onto the CerebroFlo EVD catheter compared to a competitive EVD catheter.

Indications for Use

The CerebroFlo EVD Catheter is indicated for temporary insertion into a ventricular cavity of the brain for external drainage of cerebrospinal fluid (CSF) in those patients with elevated intracranial pressure (ICP), intraventricular hemorrhage, or hydrocephalic shunt infections.

Contraindications

• This device is not designed, sold, or intended for use except as indicated.
• The ventricular catheter is contraindicated if scalp infection is present.
• A patient undergoing external drainage and monitoring must be kept under continuous, close supervision. The use of a ventricular drainage catheter is contraindicated where trained personnel are not available to supervise monitoring and drainage on a 24-hour-a-day basis.
• The ventricular catheter is contraindicated for use longer than 21 days.
• Insertion of the ventricular catheter is contraindicated in patients with coagulopathy due to prior administration of anticoagulants or antithrombotic, or who are known to have a bleeding diathesis. Coagulopathy should be corrected according to institutional protocols before insertion of an EVD.

Warnings and Precautions

Prior to surgery, the surgeon should inform the prospective patient and/or their representatives of the warnings, precautions, and possible complications associated with this product.

Use of the ventricular catheter should be considered with extreme caution for patients taking anti-platelet medications.

Improper use of instruments in the handling, insertion, tunneling or repositioning of the catheter may result in nicks, tears, punctures, slitting, breakage, or crushing of the CerebroFlo EVD components. Such damage may lead to device failure, potentially requiring device removal and replacement.

Proper aseptic technique must be followed, and care taken to prevent the introduction of foreign material onto or into the catheter. Such foreign material may result in obstruction of the catheter, foreign body reactions, allergic reactions, or infection.

Care must be taken when securing the luer connector and the suture clip to the catheter with ligatures to avoid cutting or crushing of the catheter tubing.

Patients undergoing external CSF drainage and/or ICP monitoring must be kept under continuous, close supervision for signs and symptoms of changing intracranial pressure due to excessive or insufficient drainage caused by improper drainage system adjustment or system failure. Excessive or insufficient drainage may result in potentially serious, life-threatening injury to the patient.

Correct alignment of the drainage system relative to the patient is critical for proper performance. Refer to the external CSF drainage and/or ICP system Instructions for Use for device specific alignment procedures.

Care must be taken in the routing and securing of the catheter tubing to the patient to ensure the catheter is not kinked, abraded, or unintentionally pulled from the patient.

Care must be taken when repositioning or moving the patient. Pressure level changes and patient repositioning should only be made by qualified personnel on the orders of a physician.

The physician must strongly consider removing the catheter if there are signs or symptoms of surgical site infection or meningeal irritation.

These products have not been tested for drug compatibility and therefore are not intended for drug administration.

Integra LifeSciences Corporation makes no claim for, or representation as to the performance characteristics of this product when it is used in conjunction with components of other manufacturers.