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Evaluation of a miniaturized biologically vascularized scaffold in vitro and in vivo

 
: Kress, Sebastian; Baur, Johannes; Otto, Christoph; Burkard, Natalie; Braspenning, Joris; Walles, Heike; Nickel, Joachim; Metzger, Marco

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Scientific Reports 8 (2018), Art. 4719, 13 S.
ISSN: 2045-2322
Englisch
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer ISC ()
tissue engineering; scaffold; vaskulär

Abstract
In tissue engineering, the generation and functional maintenance of dense voluminous tissues is mainly restricted due to insufficient nutrient supply. Larger three-dimensional constructs, which exceed the nutrient diffusion limit become necrotic and/or apoptotic in long-term culture if not provided with an appropriate vascularization. Here, we established protocols for the generation of a pre-vascularized biological scaffold with intact arterio-venous capillary loops from rat intestine, which is decellularized under preservation of the feeding and draining vascular tree. Vessel integrity was proven by marker expression, media/blood reflow and endothelial LDL uptake. In vitro maintenance persisted up to 7 weeks in a bioreactor system allowing a stepwise reconstruction of fully vascularized human tissues and successful in vivo implantation for up to 4 weeks, although with time-dependent decrease of cell viability. The vascularization of the construct lead to a 1.5× increase in cellular drug release compared to a conventional static culture in vitro. For the first time, we performed proof-of-concept studies demonstrating that 3D tissues can be maintained within a miniaturized vascularized scaffold in vitro and successfully implanted after re-anastomosis to the intrinsic blood circulation in vivo. We hypothesize that this technology could serve as a powerful platform technology in tissue engineering and regenerative medicine.

: http://publica.fraunhofer.de/dokumente/N-487948.html