Handchir Mikrochir Plast Chir 2018; 50(02): 93-100
DOI: 10.1055/s-0043-124674
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Biofabrikation – neue Ansätze für den artifiziellen Gewebeersatz

Biofabrication: new approaches for tissue regeneration
Raymund E Horch
1   Universitätsklinikum Erlangen, Plastische und Handchirurgische Klinik
,
Annika Weigand
1   Universitätsklinikum Erlangen, Plastische und Handchirurgische Klinik
,
Harald Wajant
2   Abteilung für Molekulare Innere Medizin Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg
,
Jürgen Groll
3   Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde Universitätsklinikum Würzburg
,
Aldo R Boccaccini
4   University of Erlangen, Dpt. Materials Science and Engineering Institute of Biomaterials
,
Andreas Arkudas
1   Universitätsklinikum Erlangen, Plastische und Handchirurgische Klinik
› Institutsangaben
Weitere Informationen

Publikationsverlauf

09/17/2017

12/06/2017

Publikationsdatum:
29. Januar 2018 (online)

Zusammenfassung

Hintergrund Das Aufkommen von Tissue Engineering (TE) in den frühen 1990er Jahren wurde durch den zunehmenden Bedarf an funktionellem Gewebe und Organersatz gefördert. Das klassische TE basiert dabei auf der Kombination von Trägermatrizen, Zellen und Wachstumsfaktoren, um verlorenes oder beschädigtes Gewebe und Organe wieder herzustellen. Trotz beachtlicher Ergebnisse in vitro und in experimentellen Ansätzen hat der Mangel an früher Vaskularisierung eine Umsetzung in die tägliche klinische Praxis bisher behindert Ein neues Forschungsfeld mit dem Namen „Biofabrikation“,. das die neuesten 3D-Drucktechnologien nutzt, zielt darauf ab, verschiedene Zellen, Biomaterialien und Moleküle hierarchisch und räumlich in eine Matrix zu integrieren, um eine gerichtete Reifung von künstlichem Gewebe zu gewährleisten.

Material und Methoden Eine Literaturrecherche der relevanten Publikationen zum Thema Biofabrikation und Bioprinting wurde mit der PubMed-Datenbank durchgeführt. Relevante Papiere wurden ausgewählt und mit einer sekundären Analyse von spezifischen Zitaten über die Bioprinting-Techniken bewertet.

Ergebnisse Es wurden 180 relevante Publikationen mit den oben genannten Schlüsselwörtern identifiziert und ausgewertet. Grundprinzipien in dem Entwicklungsfeld der Biodrucktechnologie konnten herausgefiltert werden. Die Schlüsselelemente umfassen die Hochdurchsatzanordnung von Zellen und die Herstellung von komplexen und funktionellen, hierarchisch organisierten Gewebekonstrukten. Es wurden fünf relevante technologische Prinzipien für das Bioprinting identifiziert, wie Stereolithographie, Extrusionsbasiertes Drucken, laserunterstütztes Drucken, Inkjet-basiertes Drucken und Nano-Bioprinting. Die verschiedenen technischen Methoden des 3D-Drucks wurden mit verschiedenen positiven, aber auch negativen Auswirkungen auf Zellen und Proteine während des Druckprozesses assoziiert. Die Forschungsanstrengungen in diesem Bereich zielen offensichtlich auf die Entwicklung von optimierten so genannten Biotinten und verbesserten Drucktechnologien ab.

Schlußfolgerung Diese Übersicht beschreibt die Entwicklung der klassischen Methoden des TE in der Regenerativen Medizin in das sich rapide entwickelnde Gebiet der Biofabrikation durch Bioprinting. Die Vorteile des 3D-Bioprintings gegenüber herkömmlichen Tissue Engineering-Techniken basieren auf der Anordnung von Zellen, Biomaterialien und Biomolekülen in einer räumlich kontrollierten Weise zur Reproduktion von nativen Gewebemakro-, Mikro- und Nanoarchitekturen, die nicht nur dazu genutzt werden können, funktionelle Ersatzgewebe oder Organe zu produzieren, sondern auch als neue Modelle für die Grundlagenforschung dienen. Die Nachahmung der stromalen Mikroumgebung von Tumorzellen zur Untersuchung der Tumorbildung und -progression, der Metastasierung, Angiogenese und Modulation der damit verbundenen assoziierten Prozesse ist eine dieser Anwendungen in der aktuellen Forschung. Zu diesem Zweck wird eine enge Zusammenarbeit von Fachleuten aus den Bereichen Ingenieurswesen, Biomaterialwissenschaft, Zellbiologie und rekonstruktive Mikrochirurgie notwendig sein, um zukünftige Strategien zu entwickeln, die die derzeitigen Einschränkungen des artifiziellen Gewebe-Ersatzes überwinden können.

Abstract

Background The advent of Tissue Engineering (TE) in the early 1990ies was fostered by the increasing need for functional tissue and organ replacement. Classical TE was based on the combination of carrier matrices, cells and growth factors to reconstitute lost or damaged tissue and organs. Despite considerable results in vitro and in experimental settings the lack of early vascularization has hampered its translation into daily clinical practice so far. A new field of research, called “biofabrication” utilizing latest 3D printing technologies aims at hierarchically and spatially incorporating different cells, biomaterials and molecules into a matrix to alleviate a directed maturation of artificial tissue.

Materials and Methods A literature research of the relevant publications regarding biofabrication and bioprinting was performed using the PubMed data base. Relevant papers were selected and evaluated with secondary analysis of specific citations on the bioprinting techniques.

Results 180 relevant papers containing the key words were identified and evaluated. Basic principles into the developing field of bioprinting technology could be discerned. Key elements comprise the high-throughput assembly of cells and the fabrication of complex and functional hierarchically organized tissue constructs. Five relevant technological principles for bioprinting were identified, such as stereolithography, extrusion-based printing, laser-assisted printing, inkjet-based printing and nano-bioprinting. The different technical methods of 3D printing were found to be associated with various positive but also negative effects on cells and proteins during the printing process. Research efforts in this field obviously aim towards the development of optimizing the so called bioinks and the printing technologies.

Conclusion This review details the evolution of the classical methods of TE in Regenerative Medicine into the evolving field of biofabrication by bioprinting. The advantages of 3D bioprinting over traditional tissue engineering techniques are based on the assembling of cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures, that can be utilized not only to potentially produce functional replacement tissues or organs but also to serve as new models for basic research. Mimicking the stromal microenvironment of tumor cells to study the process of tumor formation and progression, metastasis, angiogenesis and modulation of the associated processes is one of these applications under research. To this end a close collaboration of specialists from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery will be necessary to develop future strategies that can overcome current limitations of tissue generation.

 
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