Transcript Use of dendrimers as a biological sensing of mechanical

Use of Dendrimers as a Biological
Sensing of Mechanical Heart Valve
Thrombosis
“SMART” is the new trend
 Smart Phones, Smart TV, Smart Cars, Smart Houses
How SMART are medical devices?
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
60-70 years
>70 years
>80 years
11.5%
17.3%
32%
Reoperation mortality rate increases with age
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)
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.
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..
Dendrimers
Synthesis of Dendrimers
 Divergent method
 Convergent method
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.
Dendritic cavities
 The most important property of dendrimers is their ability to
encapsulate guest molecules in the macromolecule interior.
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.
Selecting a compatible dye
 Not toxic to the patient.
 Biocompatible.
 Small size to be trapped within the dendritic box
 Easily available and affordable.
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.
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.
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.
Blood clotting process
Isolating Fibrinogen Using Western Blot
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.
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.
Q&As
Thank You for Your Attention!