week 8

Question 1

3. Explain why drug-eluting stents (DES) were initially thought to be revolutionary.

Answer 1

Model Answer:
DES significantly reduced restenosis rates by inhibiting smooth muscle proliferation through local drug delivery. Early clinical data showed dramatically lower reintervention rates compared to bare-metal stents.

Question 2

1. Describe the main problem with plain old balloon angioplasty (POBA).

Answer 2

Model Answer:
POBA causes severe endothelial damage and vessel wall injury, leading to abrupt vessel closure (5–10% risk) and a strong inflammatory response. This induces smooth muscle cell proliferation and restenosis in 30–50% of patients within 6 months.

Question 3

2. What are the biological challenges in designing cardiovascular implants?

Answer 3

Model Answer:
The key challenge is dual regulation of two cell types: promoting endothelial cell recovery while suppressing smooth muscle cell proliferation. Current drugs are non-specific and affect both cell types equally.

Question 4

4. Compare and contrast bare-metal stents (BMS) with first-generation drug-eluting stents (DES).

Answer 4

Model Answer:
BMS reduce vessel recoil compared to balloon angioplasty but suffer from high rates of restenosis (30–50%) due to endothelial damage and inflammatory smooth muscle proliferation.
First-gen DES (e.g., Cypher, TAXUS) coat the stent with a drug-polymer system (sirolimus or paclitaxel) that inhibits smooth muscle proliferation, significantly lowering restenosis. However, DES delay endothelial healing, increasing late stent thrombosis risk and requiring prolonged dual antiplatelet therapy (DAPT).

Question 5

5. Discuss the reasons why fully bioresorbable stents were abandoned despite initial promise.

Answer 5

Model Answer:
Bioresorbable stents were designed to eliminate long-term adverse effects by fully degrading. However, polymers used were brittle, leading to poor mechanical strength, difficulty in deployment, fracture risk, and malapposition. These issues led to unpredictable outcomes and the eventual abandonment of major programs like Abbott’s Absorb.

Question 6

6. Which of the following is the major reason for late stent thrombosis in first-generation drug-eluting stents?
   A) Plaque progression
   B) Rapid endothelialization
   C) Incomplete endothelial healing
   D) Excessive blood pressure

Answer 6

Correct Answer: C) Incomplete endothelial healing

Question 7

7. Which metal allowed second-generation DES to have thinner struts without sacrificing mechanical strength?
   A) Stainless Steel
   B) Cobalt-Chromium
   C) Magnesium
   D) Platinum

Answer 7

Correct Answer: B) Cobalt-Chromium

Question 8

8. What is the major biological purpose of endothelial cells in the vessel wall?
   A) Secrete collagen
   B) Prevent blood clot formation
   C) Stimulate smooth muscle proliferation
   D) Cause atherosclerosis
   ``

Answer 8

Correct Answer: B) Prevent blood clot formation

Question 9

9. What is the primary cause of in-stent restenosis?
   A) Blood pressure spikes
   B) Smooth muscle cell proliferation
   C) Loss of cardiac output
   D) Failure of drug elution

Answer 9

Correct Answer: B) Smooth muscle cell proliferation

Question 10

10. Imagine you are designing a third-generation stent. List two improvements you would prioritize and justify why.

Answer 10

Model Answer:
* Thinner struts: To improve endothelialization and reduce thrombosis risk by minimizing the physical barrier to cell migration.
* Biodegradable polymer: To allow controlled drug release and eventually leave only a bare metal scaffold to minimize long-term inflammatory response and thrombosis risk.