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Interaction between 3D scaffolds and blood vessels – Implications for generation of axially vascularised bioartificial tissues

Ulrich Kneser 1Justus P. Beier Andreas Arkudas Elias Polykandriotis Oliver Bleiziffer Subha Rath Dietmar W. Hutmacher Raymund E. Horch 

1. University Erlangen, Erlangen 91054, Germany

Abstract

Vascularization is one of the major challenges in tissue engineering. Sufficient engraftment of large volume bioartificial tissues requires not only rapid ingrowth of blood vessels but also a well balanced interaction between vascularization and formation of fibrovascular tissue. Transfer of initially vascularized, functional bioartificial constructs may be facilitated by certain microsurgical approaches based on one dominant vascular axis. Arteriovenous loops or arteriovenous bundles could be applied for transformation of 3D scaffolds into axially vascularized functional tissue units. Our group developed a microsurgical AV loop model based on the saphenous artery and vein that allows generation of large amounts of vascularized tissue in small and large animals. Vascularization kinetics and differentiation of the vascular system could efficiently be modulated by immobilized angioinductive growth factors (VEGF and bFGF). The effect of these factors is dose-dependent and the drug release system has been combined with several porous 3D scaffolds for bone tissue engineering applications. Visualization of the vascular network and determination of vascularization kinetics require sophisticated imaging tools such as high resolution MRI or CT scans either for intravital or post mortem studies. Transplantation of specific adult or fetal cells (e.g. osteoblasts, myoblasts or fetal liver cells) allows generation of functional neo-tissues for applications in regenerative medicine. Application of tissue-inductive factors (BMPs) is being assessed as an alternative approach at the moment. Innovative biomimetic scaffolds with graded porosity, appropriate orientation of the internal structures, functionalized surfaces for optimal cell attachment and binding sites for angioinductive or tissue-specific growth factors will eventually allow growing large volumes of axially vascularized autologous bioartificial tissues suitable for transfer to distant defect sites.

 

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Presentation: Invited oral at E-MRS Fall Meeting 2008, Symposium L, by Ulrich Kneser
See On-line Journal of E-MRS Fall Meeting 2008

Submitted: 2008-08-18 23:14
Revised:   2009-06-07 00:48