Regenerative Medicine

Anita Mol, Carlijn Bouten, Simon Hoerstrup, Frank Baaijens

Laboratory for Tissue Biomechanics and Tissue Engineering, Department of Biomedical Engineering,

Eindhoven University of Technology

Healthcare-transforming technologies

ImagingEarlier diagnosis saves lives and

reduces costs

Minimally Invasive surgeryReducing patient trauma and reduces costs

Adapted from: Russ Coile, Futurescan 2003, SG-2

Clinical IT Right Information at the right time enables best treatment and reduces

costs

Molecular MedicinePreventing disease from happening and reduces costs

Regenerative medicineImplants taking over vital bodily functions, improving quality of life

Heart valves

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

300.000 replacements / year

Main drawback: no growth, repair and adaptation

Tissue Engineering Paradigm

Cells Scaffold(Mechanical)preconditioning

Tissue formation,matrix remodelling

Implantation/Model system

Implantation

Isolation of cells from vessels Seeding in scaffold Culture,

conditioningTissue formation

vsmc endothelial cells

Proof-of-concept: sheep cells

6 weeks

16 weeks

20 weeks

Hoerstrup et al. Circulation 2000

Not sufficient load-bearing properties to serve as aortic valve replacement

Implanted as pulmonary heart

valve replacement

Challenge

• Develop a living, autologous valve replacement, able to grow, repair and adapt to changing environment using human cells

• Sufficiently strong for aortic (high pressure) side

Strong, functional human valves!

Effective orifice area:1.52 0.21 cm2

Mean systolic gradient:11.5 3.1 mm Hg

Regurgitation:18.2 4.2 %

Dynamically conditioned tissue engineered human heart valve

Mol et al. Circulation 2006

Discussion

Tissue engineered human heart valves show promising features as aortic valve replacements

• Functional parameters are in the range of those reported for commonly used bioprostheses

• Upcoming animal studies will elucidate short- and long-term functionality of tissue-engineered heart valves in aortic position and the capability of growth and remodeling

Engineered tissues (In-vitro)

Acknowledgements

Eindhoven, BMT, TBMEDr. Anita MolDrs. Marjolein van LieshoutIr. Niels DriessenIr. Ralf BoerboomIr. Angelique BalguidIr. Rolf PullensIr. Martijn CoxIr. Mirjam RubbensChrista DamKaty KrahnDr. Carlijn BoutenDr. Marcel RuttenDr. Claudia VazDr. Gerrit PeetersProf. Bas de MolProf. Frank Baaijens

Eindhoven, BMT / ST, SMOIr. Eva WisseDrs. Patricia DankersDr. Nico SommerdijkDr. Maarten MerkxProf. Bert Meijer

Eindhoven, BMT, BEMIProf. Klaas Nicolaij

Dr. Gustav Strijkers

ZürichDr. Stephan NeuenschwanderDörthe Schmidt, MSc.Prof. Simon Hoerstrup

Leiden, TNO TPGDr. Ruud Bank

Rotterdam, Dutch Heart Valve BankDr. J. van Kats, prof. A. Bogers

GrantsBio-Initiative, Eindhoven University of Technology

Vici grant, Netherlands Organisation for Scientific Research

BioPolymers program, Dutch Polymer Institute