1. Use of Dendrimers as a Biological Sensing of Mechanical Heart Valve Thrombosis

2. “SMART” is the new trend Smart Phones, Smart TV, Smart Cars, Smart Houses

3. How SMART are medical devices?

4. Mechanical Valve Thrombosis Continuous blood tests and anticoagulant drug intake Side effects: : cloudy urine, black bowel movements, general weakness and unusual pains in the abdomen Reoperation upon late diagnosis Reoperation mortality rate increases with age 60-70 years>70 years>80 years 11.5%17.3%32%

5. Mechanical Valve Thrombosis Blood clot (thrombus) could grow large enough to affect the proper function of the valve (valve thrombosis) Or break loose (embolize) and travel with the blood to another part of the body & block blood flow to that area (thromboembolismtests)

6. Aim: Detecting Mechanical Valve Thrombosis during early stages Detecting valve thrombosis early in formation is very crucial. At that stage, non-invasive prevention techniques can be employed, such as anticoagulant treatment. This kind of limited time anticoagulant treatment is more desirable compared to constant one. It removes the necessity of constant monitoring of patient blood and substantially reduces the cost of medications and medical services.

7. Dendrimers as a biological sensing of mechanical heart valve thrombosis Dendrimers are a new class of polymeric materials. Dendrimers have a multifunctional core in the middle of the structure. They are highly branched, monodisperse macromolecules As a result of their unique behaviour dendrimers are suitable for a wide range of biomedical and industrial applications..

8. Dendrimers

9. Synthesis of Dendrimers Divergent method Convergent method

10. Properties of Dendrimers Dendrimers are monodisperse macromolecules, unlike linear polymers. Molecular mass of dendrimers can be specifically controlled during synthesis. The presence of many chain-ends is responsible for high solubility and miscibility and for high reactivity. Dendrimers have some unique properties because of their globular shape and the presence of internal cavities.

11. Dendritic cavities The most important property of dendrimers is their ability to encapsulate guest molecules in the macromolecule interior.

12. Proposition We propose to use modified poly(propylene imine) dendrimers as a coating for the implanted heart valves, which will adhere to the surface of the valve and encapsulate a guest dye molecule. Once blood coagulation is started within the proximity of these heart valves the dye molecule will be released from the dendritic cavities. Upon successful release the patient will notice the apparent change in their urine color and subsequently consult with their doctor.

13. Selecting a compatible dye Not toxic to the patient. Biocompatible. Small size to be trapped within the dendritic box Easily available and affordable.

14. Methylene blue & Rose Bengal The Rose Bengal dye is commonly used within the eye droplets in order to stain necrotic tissue and devitalized cells of the cornea in keratitoconjunctivitis sicca. It is also widely used as a liver function test. Methylene blue oral is used to treat methemoglobinemia and urinary tract infections. Methylene blue injection is used to treat methemoglobinemia.

15. Selecting compatible end groups Those end groups need to be large and dense enough in order to block the cavity entrance. They also need to be biologically inert. Easily cleaved once the blood coagulation is initiated at the site of the heart valves.

16. Selecting compatible end groups Many enzymes are present which are unique to the coagulation process and otherwise are not found in the blood plasma. Trombin converts during the coagulation process passive Fibrinogen to functional Fibrin. Trombin is unique to this process and otherwise is found in inactive form of Trombinogen. The end groups of dendrimers can be modified to be polypeptide sequences analogous to the Fibrinogen cleavage side, which Trombin recognizes. The activated Trombin will cleave the end groups of the dendrimers, thus releasing the dye molecule from the dendritic cavity.

17. Blood clotting process

18. Isolating Fibrinogen Using Western Blot

19. Impact & Further research Early detection of blood coagulation using dendrimers may give rise to numerous researches in this area. It is relatively inexpensive compared to current methods. There is not many long term biological sensing mechanisms, that can work autonomously within the human body, without intervention of doctors. Right now, the proposed mechanism deals with the detecting the heart valve thrombosis and alerting the patient via colorizing their urine.

20. Impact & Further research If this mechanism proves to be successful, future research groups may focus not only on detection, but also on taking the preventive actions by the device itself. Dendrimers have been used as a drug delivery medium previously. They may be used to release anticoagulant drugs when the formation of thrombosis is taking place. Several different methods maybe combined together with the proposed one in order to make the next-generation devices smarter.

21. Q&As

22. Thank You for Your Attention!