Tissue Engineering: Herausforderung für in-vitro Methodenentwicklung

The success of tissue engineering depends on two principal factors, namely the ability to produce functional implants and to control the sequelae of implantation. There are various ways to achieve functional implants, such as the implantation of cells, administration of bioactive substances, like growth factors, or chemically-defined matrices such as ceramics. For practical purposes it is probable that a combination of these approaches will prove effective. With regard to the choice of matrix, both permanent scaffolds and, even more attractive, a biodegradable matrix, which would yield 1 Q BlOmatenalien 3 (1), 2002 C. James Kirkpatrick: Tissue Engineering ORIGINAL! ARBEITEN biocompatible degradation products, could be employed. A central problem with tissue engineering applications at the moment is our knowledge deficit concerning the optimal degree of inflammation and repair required to give effective biocompatibility. This leads to the consequence that more sophisticated in vitro methods are required, not just to create functional implants, but also to understand the complexity of the host reaction to such implants in order to control it. This paper discusses the pathobiological basis of such reactions as a pointer to the rational development of in vitro test methods, illustrating this from the literature as well as from our own laboratory data. Future developments will involve the possible use of stem cells, and in the regulation of tissue reactions to implantation increasingly the incorporation of pharmaceuticals in so-called drug delivery systems. The approach of gene therapy will in due course find its application, although this could take much longer than some protagonists might admit. Such methods could offer the possibility of targeting desired responses and inhibiting negative reactions. Nevertheless, despite the general euphoria about this promising technology, it is advisable from a pathobiological viewpoint to guard against excessive expectations with respect to an adequate physiological function of tailored hybrid organs. Literatur [1] Ali S.A. , Zhong S.P., Doherty P.J., Williams D.F. : Mechanisms of polymer degradation in implantable devices. I. Poly(caprolactone). Biomaterials 14: 648-656, 1993 [2] Al-Saffar N„ Mah J.T. , Kadoya Y„ Revell P.A. : r e v a s cularisation and the induction of cell adhesion molecules in response to degradation products from orthopaedic implants. Ann Rheum Dis 54: 201-208, 1995 [3] Andriano K.P., Tabata Y„ Ikada Y„ Heller J.: In vitro and in vivo comparison of bulk and surface hydrolysis in absorbable polymer scaffolds for tissue engineering. J Biomed Mater Res 48: 602-612, 1999 [4] Angele P., Kujat R„ Nerlich M„ Yoo J., Goldberg V. , Johnstone B. : Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge. Tissue Eng 5: 545-554, 1999 [5] Anselme K„ Linez P., Bigerelle M„ Le Maguer D. , Le Maguer Α. , Hardouin P., Hildebrand H.F, lost Α. , Leroy J.M. : The relative influence of the topography and chemistry of TiAl6V4 surfaces on osteoblastic cell behaviour. Biomaterials 21: 1567-1577, 2000 [6] Bazzoni G. , Dejana E. , Lampugnani M.G. : Endothelial adhesion molecules in the development of the vascular tree: the garden of forking paths. Curr Opin Cell Biol 11: 573581, 1999 [7] Bhatia S.N. , Balis U.J., Yarmush M.L. , Toner M. : Probing heterotypic cell interactions: hepatocyte function in microfabricated co-cultures. J Biomater Sei Polym Ed. 9: 11371160, 1998 [8] Black A.F, Berthod F. , L'heureux N. , Germain L. , Auger F.A. : In vitro reconstruction of a human capillary-like network in a tissue-engineered skin equivalent. FASEB J. 12: 1331-1340, 1998 Prof. Dr. C. James Kirkpatrick Korrespondenzanschrift: Prof. Dr. C. James Kirkpatrick, MD, PhD, DSc Institut für Pathologie Klinikum der JohannesGutenberg-Universität Langenbeckstr. 1 55101 Mainz Akademischer Lebenslauf 1968-1978