Lecture 10. (CardiacTE_Slide2026.pdf) )Biophysics 2 and Cardiac Tissue Engineering

Why is cardiac tissue engineering clinically needed?

Because cardiovascular disease is a leading cause of death, ischemic injury causes non-functional scar tissue, and donor hearts are very limited.

What is the main aim of cardiac tissue engineering?

To replace or repair damaged heart muscle using lab-grown cardiac tissue as an alternative to transplantation.

What are the major tissue layers of the heart shown in the lecture?

• Endocardium

• Myocardium

• Epicardium

• Pericardium

What cell types are found in cardiac tissue?

Examples include:

• cardiomyocytes

• cardiac fibroblasts

• endothelial cells

• pericytes

• MSCs

• endocardial cells

• epicardial cells

• vascular smooth muscle cells

What does EMT mean in the cardiac context?

Epithelial-to-mesenchymal transition, involved in repair and fibrosis.

What are the main structural features of cardiac muscle?

It is:

• highly organized

• anisotropic

• striated

• branching
  with intercalated discs between cells.

What is the role of desmosomes in cardiac muscle?

They provide mechanical force transmission and tissue integrity.

What is the role of gap junctions in cardiac tissue?

They allow fast electrical conduction between cells for synchronous contraction.

What is excitation-contraction coupling (ECC)?

The process linking electrical excitation of cardiomyocytes to calcium-dependent contraction.

Where does the heartbeat originate?

In the sinoatrial node (SAN), which generates the action potential.

What is a key feature of the cardiac muscle cell action potential?

It has a resting membrane potential around -90 mV and a characteristic plateau phase.

What are the main components of cardiac ECM?

• Collagen I and III

• elastin

• laminin

• fibronectin

• GAGs

What does cardiac ECM do?

It guides cell organization and function, provides support, and regulates cell-ECM signalling through integrins.

What is cardiac mechano-electrical feedback (MEF)?

It is the influence of mechanical forces on the heart’s electrical rhythm.

How do cardiomyocytes respond to increased mechanical stress?

They can undergo hypertrophy and other short- and long-term molecular changes.

What substrate stiffness best supports mature cardiomyocyte structure in the lecture example?

About 10 kPa.

What happens to cardiomyocytes on substrates that are too soft or too stiff?

• Too soft: sarcomeres are poorly organized

• Too stiff: more stress fibres and loss of proper sarcomere formation

What kinds of cell sources are needed for clinical cardiac TE?

Ideally human, autologous, pluripotent sources that can generate cardiomyocytes.

What is a major limitation of embryonic stem cells in cardiac TE?

Ethical concerns and risk of uncontrolled differentiation.

What is a key limitation of adult MSCs in cardiac repair?

Poor engraftment due to ischemia, inflammation, washout, and anoikis.

Why were skeletal myoblasts problematic in cardiac TE?

They do not electrically couple well and can cause arrhythmias.

What are the main advantages of iPSC-derived cardiomyocytes?

They are:

• potentially unlimited

• patient-specific/autologous

• able to generate atrial, ventricular, and pacemaker-like cells

What is the main limitation of iPSC-CMs?

They are immature/fetal-like and need electrical, mechanical, and biochemical maturation cues.

What is the purpose of a cardiac patch?

To be placed on the epicardial surface after infarction to support pumping and long-term remodeling.

What are the main cardiac patch strategies mentioned?

• Cell entrapment

• Cell sheet technology

• 3D scaffolds

What are the main advantages of scaffolds over direct cell injection?

They provide:

• a 3D environment

• delivery of multiple cell types

• a platform for growth factor delivery

What properties should an ideal cardiac scaffold have?

• bioactive surface chemistry

• large interconnected pores

• biocompatibility/wettability

• appropriate biodegradability

• cardiac-like mechanical and electrical properties

Why are electrically conductive scaffolds useful in cardiac TE?

They improve electrical signal propagation, connexin-43 expression, sarcomere organization, and synchronous beating.

Why is electrospinning useful for cardiac patches?

Because it creates ECM-like nanofibres with high surface area, interconnectivity, and tunable structure, ideal for conductive and active materials

Why are piezoelectric materials promising in cardiac TE?

Because they convert mechanical stimulation into electrical cues, supporting cardiomyocyte maturation and electrophysiology without external power.