Biomaterials for CVD Flashcards
Describe features of heart failure.
– The heart is a complex organ with different cell types, including the cardiac muscle (myocardium).
– MI results in muscle loss due to hypoxia induced as a result of blocked vessels. The inflammatory response will cause remodelling of the myocardium into fibrous tissue.
– It also alters the ECM contents in the myocardium, reducing contractile function, thinning of walls, oedema (water loading) and eventually leading to heart failure.
– There are many ways to try and fix this at different stages:
o Drugs – that prevent damaging compensation mechanisms of heart, e.g. beta blockers.
o Gene therapy.
o Valve repairs
o Artificial heart devices, Cardiac resynchronisation therapies etc.
o Transplantation – successful but difficult to find donors.
–> Transplantation is the only cure for end stage heart failure – and shortage of donated organs means there’s a lot of interest into myocardium tissue engineering.
What are the advantages of myocardium tissue engineering.
- While myocytes can be regenerated, the heart cannot deal with the number of them lost in a MI – since there isn’t much regeneration occurring. In a medium size myocardial infarction, 2x10^9 cardiomyocytes are lost.
- Originally rat cardiomyocytes were used in tissue engineering. Now we need to establish a human source - stem cells are desired as they can self-renew.
- True cardiomyocytes need to be formed or the stem cells will be dangerous to the heart.
What were the candidate stem cells for myocardium tissue engineering? Why did they fail?
- Bone marrow stem cells – only reduced the ventricular ejection fraction by 3% which is hardly noticeable.
- - This is because 90-99% of cells were lost in minutes – the heart ejects very fast and the cells are washed away before they can cross the endothelium barrier. - Adult progenitor cells – little profilerative and myogenic potential.
- - Embryonic stem cells and induced pluripotent stem cells (iPS) produced true cardiomyocytes. - Embryonic stem cells – Limited by their problem with ethics and with immune matching.
- iPS (induced pluripotent cells) –> derived from fibroblasts and used in transplantation and cell model systems. Found to be the best match.
Why were iPS preferred for tissue engineering? How and why were they matured?
Advantages of iPS:-
- They have the same properties as cardiomyocytes, these properties include spontaneous beating, transients in calcium and electrical activity.
- the stem cells can be prepared in advance – immediate availability.
- Unlimited supply due to their regeneration.
- Can form true cardiomyocytes as well as vessels and connective tissues.
- Can mature and have responses similar to adult cardiomyocytes.
- -> A lot of effort is used to make them as mature as possible before they are applied to heart to prevent mismatch. If they are immature they will trigger arrhythmias due to a lack of homogeneity.
- How do we mature them?
- Biomaterials are used in structured constructs to enhance maturation of the IPS cells.
- Polymers are used with microgrooves in the mould, to force the cells to align as they would in the heart.
- In a structured environment, the IPS will act more like mature cardiomyocytes such as in calcium transient release.
Why are patches sometimes used?
Patches are used to deliver stem cells to the heart:-
- A biomaterial is used, with cells attached to it to home them all in same way.
- This avoids the stem cells homing in different ways (and some won’t have the ability) and prevents the differentiated stem cell cardiomyctes blocking microcirculation as they are now larger. This would make intramyocardial injection inefficient.
- Therefore patch is used to enhance integration of stem cells in the heart.
What kind of compounds can be used for the patch?
- Natural occurring compounds – usually biocompatible, porous and biodegradable. However have poor strength and processibility as well as risk of immunologic response.
- Biodegradable synthetic polymers – off shelf availability, good biocompatibility and bioresorbable. Can be engineered to have good mechanical support etc. However can be inflammatory if they release toxins and can lose their mechanical properties after degradation. E.g. PED and PGS
- Non-degradable synthetic polymers – No foreign body reactions, but their effect on long term presence in body is unknown.
