an overview of cardiac tissue engineering, with examples of applications.

1. CARDIAC TISSUE
ENGINEERING
BY
MARYAM IDRIS MUSA (20142926)

2. Overview
 Introduction
 Biomaterials
 Cells
 Biomolecule
 TE product requirements
 Heart valves
 Blood vessels
 Myocardium

3. Introduction
 Heart disease is the leading cause of death and disability all over the world accounting for
approximately 40% of all human mortality
 Treatment limitations:
 Cardiomyocytes cannot divide to replace injured cells
 Restricted intrinsic capacity of the heart
 Lack of organs for transplantation and
 Complications associated with immune suppressive treatments
 The main targets for tissue engineering
 Blood vessels
 Heart muscles- myocardium and
 Heart valve

4. Biomaterials
Most commonly used biomaterials for
cardiovascular tissue engineering are
 Biodegradable Polymeric scaffolds
(Polyglycolic acid PGA)
 Hydrogels(seeded with collagen,
fibrin, alginate)
 Decellularized tissue
(composed of natural ECM proteins:
collagen, fibronectin etc.)

5. Biomaterials-Scaffolds
Scaffold provides structure for
cells/tissue to grow and deliver
biomolecules (growth factors,
cytokines, etc.)
Properties (chemical, mechanical,
biological) should be adjusted to
provide appropriate performance.

6. Cells
Cell types most commonly used for cardiac tissue
engineering (smart 2008)
 Embryonic stem cells
 Bone marrow- derived mesenchymal stem cells
 Skeletal myoblasts
 Induced pluripotent stem cells
 Multipotient adult germline stem cells
 Endothelial progenitor stem cells
 Very small embryonic-like stem cells
 Endogenous cardiac stem cells

7. Mesenchymal Stem Cells
 Found in many tissues and organs
 Are multipotent and possess
extensive proliferation potential
 Bone marrow-derived adult stem
cells can be differentiated to many
cell types like cartilage bone and
adipose fat
 Use of adult stem cells allows
autologous cell transplantation

8. Embryonic Stem Cells
 Collected at the
blastocyst stage (day 6)
of embryogenesis
 Can differentiate into
cells from all three germ
layers of the body (
endoderm, endoderm,
mesoderm)
 Capable of self-renewal
and undifferentiated
proliferation in culture for
extended time.

9. BIOMOLECULES
 Angiogenic Factors
 Vasculogenic Factors
 Growth Factors
 Differentiation Factors

10. TE Product Requirements
 Biocompatible
Should not elicit immune or inflammatory response
 Functional
Adequate mechanical and hemodynamic function, mature ECM, durability
 Living
Growth and remodelling capabilities of the construct should mimic the native heart
valve, blood vessel or myocardium structure

11. Continued
 Blood Vessels
 Must be able to withstand high-pressure fluid dynamics, turbulence
 Biocompatible, functional, living
 Valves
 Must be able to operate in a very dynamic and severe environment
 Open and close at 1Hz, exposed to mechanical stresses, high pressure fluid
dynamics, turbulence etc.
 Myocardium Patch
 High vascularity is critical
 Mechanical and electrical anisotropy
 High metabolic demand

12. Overview
Tissue engineered
construct
Cells
Scaffolds Signals
Autologous
Allogeneic
Xenogeneic
Stem
Growth factors
Cytokines
Mechanical
stimulation
Differentiation factorsNatural
Synthetic

13. Tissue Engineered Heart Valves
The heart consists of four chambers two atria
9upper chamber), two ventricles(lower ventricles)
Valves are flaps that are located on each end of
the two ventricle (lower chamber) of the heart
Valves prevent backward flow of blood
As the heart muscle contracts and releases, the
valves open and shut, letting blood flow into the
ventricles and atria at alternate times

14. What's being used for TEHV:
Cells
Vascular cells
Valvular cells
Stem cells
Scaffolds
Synthetic (PLA, PLGA)
Natural (collagen, HA, fibrin)
Decellularised biological matrices
Mechanical stimulation
Pulsatile flow systems
Cyclic flexure bioreactors

15. Tissue Engineered Blood Vessels
TEBV has become necessary because
 Atherosclerosis, in the form of coronary artery
disease results in over 515,000 coronary artery
bypass graft procedures a year in the United
States alone
 Many patients do not have suitable
vessels due to age, disease, or previous
use
 Synthetic coronary bypass vessels have not
performed adequately to be employed to any
significant degree

16. What is being used for TEBV:
Cells
Endothelial cells
Smooth muscle cells
Fibroblasts and Myofibroblasts
Genetically modified cells
Stem cells (MSCs ESCs)
Scaffolds
Synthetic(PET, ePTFE, PGA, PLA, PUs)
Natural (collagen)
Decellularized biological matrices
Mechanical Stimulation
Pulsatile Flow Systems
Cyclic longitudinal strain
Signalling Factors
Growth Factors (bFGF, PDGF, VEGF)
Cytokines

17. Bypass Vascular Grafts

18.  Graft fabrication requires designs of a suitable mold
 Walls are cellularized with smooth muscle cells
 Lumen is cellularized with endothelial cells

19. Tissue Engineered Myocardium
Overview: Myocardial Infarction
 One or more regions of the
heart muscle experience a
severe and prolonged
decrease in oxygen supply
because of insufficient
coronary blood flow
 The affected muscle tissue
subsequently becomes
necrotic

20. Myocardial Patch
Cells
Cardiocytes
Cardiac progenitor cells
Skeletal muscle cells
Smooth muscle cells
Stem cells (MSCs ESCs)
Scaffolds
Synthetic (PEG 3d MMP- responsive
hydrogel)
Natural
(collagen, ECM proteins, alginate)
Cell sheets
Mechanical Stimulation
Pulsatile Flow Systems
Rotational seeding
Cyclic mechanical strain
Signalling Factors
Growth Factors
(Insulin, transferrin, PDGF,5-azacytidine)
Cytokines
Conditioned media
Co-culture

22. Recent Developments
 Researchers at the Brigham and Women's Hospital and Harvard Medical School in
Boston and the University of Sydney in Australia were able to combine a novel elastic
hydrogel with micro scale technologies to create an artificial cardiac tissue that
mimics the mechanical and biological properties of the native heart. Which can be
used to address the challenge of engineering complex 3D- tissues as in heart tissues.
 Harvard scientists have merged stem cell and “organ-on-a-chip” technologies to
grow, for the first time, functioning human heart tissue carrying an inherited
cardiovascular disease.
 Previous studies have shown that cardiomyocytes can grow on porous scaffolds
such as gels made from alginate or gelatin. However, these materials are poor
conductors. To make a conductive scaffold, Khademhosseini and his colleagues,
including Xiaowu (Shirley) Tang of the University of Waterloo,

23. Continued…
in Ontario, enveloped carbon
nanotubes in a crosslinked gelatin film.
The team coated the nanotubes with
gelatin modified with methacrylate
monomers. They then shone light on the
nanotubes to crosslink the
methacrylate, producing a hydrogel.
The nanotubes formed a fibrous
network that connected pores of the
gel. These nanotube strands mimic
conductive fibers in heart muscle called
Purkinje fibers
Heart Scaffold
Carbon nanotubes (thin strands) form fibrous
networks in a porous hydrogel. Researchers used
this material to grow cardiac tissue in the lab.
Credit: ACS Nano

24. Conclusion
 Despite all the work being carried out for
decades, a lot still need to be done in Taking
these tissue engineered constructs
from benchtop to bedside
 Better understanding the human body and how
to manipulate cells

25. References
 www.sciencedirect.com
 An introduction to Biomaterials. Ramaswami, P and Wagner, WR. 2005
 www.seas.Harvard.edu
 Roger, v et al. heart disease and stroke statistics.2011. update: a report
from the American Heart association. Circulation. 2011
 www.sciencedaily.com Building heart tissue that beats: Engineered tissue
closely mimics natural heart muscle March 12, 2014