Frank Baaijens et al. Laboratory for Tissue Biomechanics and Tissue Engineering, Department of Biomedical Engineering, TU/e Simon Hoerstrup et al. Laboratory for Tissue Engineering and Cell Transplantation , Clinic for Cardiovascular Surgery, University Hospital Zurich Bert Meijer et al. Laboratory for Macro-Molecular and Organic Chemistry, Department of Biomedical Engineering, TU/e Jan Feijen et al. Polymer Chemistry and Biomaterials, Department of Chemical Engineering, UT Polymers for health care Polymers for functional tissue engineering of cardiovascular substitutes
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Frank Baaijens et al. Laboratory for Tissue Biomechanics and Tissue Engineering, Department of Biomedical Engineering, TU/e Simon Hoerstrup et al. Laboratory.
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Frank Baaijens et al.Laboratory for Tissue Biomechanics and Tissue Engineering, Department of Biomedical Engineering, TU/e
Simon Hoerstrup et al.Laboratory for Tissue Engineering and Cell Transplantation, Clinic for Cardiovascular Surgery, University Hospital Zurich
Bert Meijer et al.Laboratory for Macro-Molecular and Organic Chemistry, Department of Biomedical Engineering, TU/e
Jan Feijen et al.Polymer Chemistry and Biomaterials, Department of Chemical Engineering, UT
Polymers for health carePolymers for functional tissue engineering
of cardiovascular substitutes
• All procedures that restore missing tissue in patients require some type of replacement structure.
• Traditionally: totally artificial substitutes, nonliving processed tissue, or transplantation.
• New alternative, tissue engineering: the replacement of living tissue with living tissue, designed and constructed for each individual patient.
• Cardiovascular substitutes market estimated at 80 B€.
Tissue Engineering (The Lancet)
Small diameter vascular graft
Tunica media
• Cardiovascular disease leading cause of adult death
• No synthetic vascular graft available for diameters < 6mm
Thrombogenicity
Neo-intima hyperplasia (excessive proliferation of SMCs)
external elastic lamina
smooth muscle cells
internal elastic lamina
endothelium
Aortic heart valve
Valve replacements
Artificial durability remarks
mechanical life-long trombogenic, noise
synthetic ? mechanical and hemodynamical behaviour ok
Biological
xenograft 7-10 yr Chemical fixation
allograft 7-10 yr Donor dependent
autograft > 15 yr Pulmonary valve transplant
No growth, no repair and adaptation to functional demands
• 300,000 heart valve replacements each year
• Open and close 100,000 times each day, 3 billion in a lifetime
TE valves: Chain-of-Knowledge
Implantation
Cells Scaffold(Mechanical)preconditioning
Tissue formation,matrix remodelling
Implantation/Model system
Isolation of cells from vessels
Seeding in scaffold Culture, conditioning
Tissue formation
vsmc endothelial cells
Challenges
Create functional, living cardiovascular tissues: strong: collagen structure elastic: elastin network non-thrombogenic: endothelial lining three dimensional tissue architecture
external elastic lamina
smooth muscle cells
internal elastic lamina
endothelium
Role of scaffold
• Initial attachment of cells (shape)
• Supply the tissue with sufficient strength
• Bioactivity to control 3D architecture modulate proliferation and differentiation modulate ECM synthesis and degradation stimulate angiogenesis (vasculature)
time
scaffold degradation
ECM remodeling
load
bea
ring
prop
.
implantation ?
Tissue engineering of heart valves
• Successfully implanted at pulmonary site in juvenile sheep