Vascular tissue Flashcards
Large vessels: graft
Small vessels (2-5mm): more challenging and solution has not been produced
Vessel has 3 main layers that has not been successfully engineered
Coronary artery has an elastic layer that allows aorta to absorb changes in pressure in systole and diastole
Away from heart elasticity decreases and muscle increases
Vascular tissue engineering: why, current treatments, issues
Highly expensive; billions spent annually in treatment and lost economic activity
Leading cause of death, and so requires intervention.
Atherosclerosis: build up of fat, cholesterol and other substances on artery walls, which leads to plaque formation in coronary arteries (supply blood to heart), narrowing lumen size and restricting blood flow, decreasing efficiency of oxygen delivery
Can lead to angina, myocardial infraction and stroke
Tissue death from ischaemia
Multiple factors influence risk of heart disease as it is a complex disease that we don’t fully understand the onset of
Risk factors of heart disease:
Exercise
Diet
Genetics
Current treatments: dietary and lifestyle changes, drugs for stable angina, blood pressure control, statins for prevention
-Coronary artery bypass graft: harvest vein from ex. leg and connecting to aorta and joining to region previously blocked
Downsides:
Patient may not have suitable vessels for bypass, likely if they have atherosclerosis
Heart and lungs are stopped, chest is opened up so long recovery period and highly invasive
-Percutaneous coronary intervention: Radial artery on arm has a catheter inserted to deliver wire with balloon and metal stent. At blockage site balloon is expanded to open up and stent inserted for radial support
Current applied engineered vascular tissue. Why is this not used as coronary artery
Aortic aneurysm treatment: Vessel is cut out and polyester tube to replace vessels near belly button
Issues:
-Doesn’t respond to changes in temperature the same as before
-Leads to hypertension
-Graft infection
As a coronary artery (<6):
-Low patency (doesn’t require blood as required)
-High failure rate (block over time since too narrow
-Thrombosis (leads to artery blockage)
-Intimal hyperplasia (causes plaque deposits)
-May have no suitable vessels from elsewhere in body, so can’t treat certain patients
Hemodialysis: method, issues, reasons to research for coronary heart vessel
Artery and vein in forearm are connected and high pressure arterialises vein
After a few weeks that site can be accessed and blood filtered through a hemodialyser to replace function of kidney and blood returned back
Intermal hyperplasia: artery can fail with repeated access so may need synthetic fistulas
Directly replacing coronary artery has large consequence. An issues will cause heart attack which if survival still induces significant morbidity.
Instead engineer AV valve as proof of function
Requirements for an engineered coronary artery
Endothelial cells:
Permeable
Vascular tone; control of contraction and relaxation (response to pressure wave from pulse or physiological demands)
Thromboresistance (recognised by platelets and other components in blood to prevent clotting)
Inflammatory and immune regulation
Elastic lamina:
ECM components are important
Collagen
Elastin
Smooth muscle cells:
Contractibility
structural integrity
Ability to remodel
Metabolism
Adventita:
Fibroblasts
Mechanical properties
Contains vasa vasorum; small blood vessels that supply or drain the walls of the artery
Remodelling
Overall:
-Structural integrity to allow suturing and a seal to form (no leaks)
-Resist platelet adhesion (drives blood clots and thrombosis) which blood does in a foreign environment outside of vessel.
Requirements to mass produce engineered coronary artery treatment
Manufacture at scale
Quality control (reproducible with high accuracy)
Reasonable price
Robust data
Shelf life
Short development time (allows clinical application)
Sufficient cell source
Behaves like in vivo aorta (else introduces clinical problems)
Personalisation
All has to be better than current technology to be worth taking risk of new treatment over current
Where to source cells
Scaffold that allows cell to adhere and maintain function
Source cells
Maturation period with variety of stimuli in bioreactor
Sparks mandrel approach; using body as natural bioreactor
Implant rod under skin in pouch for up to 12 weeks
Body recognises as foreign and initiates foreign body response
Secreted ECM fibrous tissue to coat and protect body from material
Extract, removed rod to obtain natural cell structure
Downsides:
Not biological active like vessel: no endothelial cells or smooth muscle cells, etc
Decellularise tissue from animal as xenogenic source. Seed with cells and allow ECM to induce cell responses to form tissue. Direct implantation will cause rejection
Not yet at clinical application for vessels in humans
Synthetic
Roll up sheet of polymer
Electrospinning to produce fibrous structure around metal mandrle
Matrix moulding; pour material into mould, allow to set, implant
Dip metal rod into hydrogel and subject to crosslinking (rapid manufacture and repeatable)
Methods to implement endothelial cells into scaffold
Endothelialise in vivo
Seed endothelial cells onto surface
Tubulra structure is spun as endothelial cells are added in a stream to ensure complete coverage
Functionalise surface to attach cells of a specific type
Introduce PDGF, VEGF, etc
