Presentation on theme: "Anita Mol, Carlijn Bouten, Simon Hoerstrup,"— Presentation transcript:
1 Anita Mol, Carlijn Bouten, Simon Hoerstrup, Regenerative MedicineAnita Mol, Carlijn Bouten, Simon Hoerstrup,Frank BaaijensLaboratory for Tissue Biomechanics and Tissue Engineering,Department of Biomedical Engineering,Eindhoven University of Technology
2 Healthcare-transforming technologies Minimally Invasive surgery Reducing patient trauma and reduces costsImaging Earlier diagnosis saves lives and reduces costsClinical IT Right Information at the right time enables best treatment and reduces costsMolecular Medicine Preventing disease from happening and reduces costsRegenerative medicine Implants taking over vital bodily functions, improving quality of lifeAdapted from: Russ Coile, Futurescan 2003, SG-2
3 Heart valvesThe aortic heart valve is one of the four valves in the heart. It is situated at the outlet of the left ventricle and controls the unidirectional blood flow from the ventricle to the aorta.The valve consists of three leaflets, three sinuses and the aortic ring, which forms the line of attachment of the leaflets to the aortic wall. The leaflets form cusps that closely fit together during closure of the valveThe valve opens and closes about times a day and 3.7 billion times in a lifetime and you can imagine that this requires strength, durability and flexibility of the tissue.Pathological changes due to congenital abnormalities, rheumatic fever, or calcification may result in stenosis, (restriction of the opening of the valve), or insufficient closure, causing back flow or regurgitation. These conditions increase the workload for the heart and compromise cardiac function. In severe cases heart valve dysfunction is treated with replacement of the valve with a prosthesis.
4 Valve replacements Main drawback: no growth, repair and adaptation replacements / yearThe annual number of heart valve replacements is 170 thousand. Currently used prostheses used are either artificial or biological in nature. As you will probably know mechanical valves, like the tilting disk or bileaflet valves, are time resistant but trombogenic and require life long anticoagulation therapy.Main drawback: no growth, repair and adaptation
5 Tissue Engineering Paradigm CellsScaffold(Mechanical)preconditioningTissue formation,matrix remodellingImplantation/Model systemImplantationIsolation of cells from vesselsSeeding in scaffoldCulture,conditioningTissue formationvsmcendothelial cellsTo overcome this problem tissue engineered heart valves are being developed. Above you see the general roadmap for tissue engineering, below specific protocols for heart valve engineering.These valves consist of autologous cells, for instance isolated from blood vessels, which are seeded on a biodegradable scaffold with the typical valve geometry and cultured under conditions that mimic the physiological in-vivo environment. This is typically done in a so-called bioreactor. The scaffold provides initial anchorage and support for the cells, until they have produced and reorganized their own extracellular matrix to form a functional tissue. By that time, ideally, the scaffold should be fully degraded to obtain a completely autologous valve. This may be achieved before or after implantation.
6 Proof-of-concept: sheep cells Hoerstrup et al. Circulation 2000Implanted as pulmonary heart valve replacement6 weeks16 weeks20 weeksNot sufficient load-bearing properties to serve asaortic valve replacement
7 ChallengeDevelop a living, autologous valve replacement, able to grow, repair and adapt to changing environment using human cellsSufficiently strong for aortic (high pressure) side
8 Effective orifice area: Mean systolic gradient: Strong, functional human valves!Mol et al. Circulation 2006Effective orifice area:1.52 0.21 cm2Mean systolic gradient:11.5 3.1 mm HgRegurgitation:18.2 4.2 %Dynamically conditioned tissue engineered human heart valve
9 DiscussionTissue engineered human heart valves show promising features as aortic valve replacementsFunctional parameters are in the range of those reported for commonly used bioprosthesesUpcoming animal studies will elucidate short- and long-term functionality of tissue-engineered heart valves in aortic position and the capability of growth and remodeling
11 Acknowledgements Eindhoven, BMT, TBME Eindhoven, BMT / ST, SMO Dr. 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 BaaijensEindhoven, BMT / ST, SMOIr. Eva WisseDrs. Patricia DankersDr. Nico SommerdijkDr. Maarten MerkxProf. Bert MeijerEindhoven, BMT, BEMIProf. Klaas NicolaijDr. Gustav StrijkersZürichDr. Stephan NeuenschwanderDörthe Schmidt, MSc.Prof. Simon HoerstrupLeiden, TNO TPGDr. Ruud BankRotterdam, Dutch Heart Valve BankDr. J. van Kats, prof. A. BogersGrantsBio-Initiative, Eindhoven University of TechnologyVici grant, Netherlands Organisation for Scientific ResearchBioPolymers program, Dutch Polymer Institute