Zusammenfassung
Behandlungen therapiebedingter Knochendefekte stellen vor dem Hintergrund des demografischen Wandels in den industrialisierten Ländern, d. h. der Überalterung der Bevölkerung, eine zunehmende Herausfor-derung dar. Die Wiederherstellung eines Knochenareals ist elementarer Bestandteil der rekonstruktiven Chirurgie. Die Verwendung körpereigenen Gewebes ist aufwendig und mit Risiken verbunden. Betroffen sind hier vor allem Patienten, bei denen aufgrund von Vorerkrankungen oder Vorbehandlungen schlechte vaskuläre Verhältnisse vorliegen und somit das Einheilen eines Transplantates erheblich gefährdet ist. Knochenersatzmaterialien führen vor allem bei größeren De-fekten häufig zur Bildung eines minderwertigen Knochenlagers. Durch Wachstumsfaktoren kann die körpereigene Knochenheilung sowie die Osseointegration alloplastischer Implantate erheblich verbessert bzw. beschleunigt werden. Aufgrund der hohen Therapiekosten und kurzen Halbwertszeiten gilt das Interesse verstärkt den Alternativen wie verschiedenen Formen des Gentransfers. Entsprechende Freisetzungssysteme haben hierbei aus verschiedenen Gründen eine erhebliche Bedeutung.
Summary
In the context of demographic changes in industrialized countries, especially due to the aging population, treatment of therapyrelated bone defects provides an increasing challenge. The restoration of a bone defect area is an integral part of reconstructive surgery. Using the body's own bony tissue is costly, invasive and therefore associated with risks for the patient. Here mainly patients are problematic presenting with pre-existing medical conditions or poor vascular supply due to pretreatments. So the ingrowth of autologous grafts can significantly be compromised. Especially in cases of larger defects alternative bone replacement materials often lead to the formation of an insufficient bone quality and therefore do not provide a suitable concept. By the application of growth factors like bone morphogenetic proteins (BMPs) the body's own bone healing capacity and also the osseointegration of alloplastic implants can considerably be improved respectively accelerated. In many animal models as well as in clinical applications the subgroup of BMPs has demonstrated their high potential to induce de novo bone formation in various tissues. Even though several materials, mainly demineralised bone matrices, hydroxyapatite, tricalcium phosphate, poly-lactic acid and collagens have been analysed as potential carriers but the delivery still remains problematic. As none of the latter is able to provide a sustained, continuous release of these factors at the region of interest and growth factors themselves have short half-lives caused by diffusion and degradation processes and due to the high costs of every cytokine therapy the interest is amplified in alternatives such as various forms of gene transfer. Genes encoding different growth factor proteins can directly be delivered to the target cells. Transfected cells serve as local “bioreactors”. For various reasons appropriate delivery systems are here of considerable importance. This review refers to current experimental and clinical applications and identifies different in vivo as well as ex vivo approaches for cell transfection and transduction. Explaining the underlying biological basis, the focus is on different innovative methods providing alternatives to the direct application of cytokines.
Schlüsselwörter
Wachstumsfaktoren - Gentransfer - Knochenregeneration - Freisetzungssysteme
Keywords
Growth factors - gene transfer - bone regeneration - drug delivery systems
