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A. Ovsianikov, V. Mironov:
"Tissue Spheroids Encaged into Rigid Microscaffolds - The Third Strategy in Tissue Engineering";
Keynote Lecture: Bayreuth Polymer Symposium, Bayreuth (invited); 2015-09-20 - 2015-09-22.

In addition to the classical scaffold-based tissue engineering, a scaffold-free strategy, relying on the directed tissue self-assembly with tissue spheroids or microtissues as building blocks, has been developed within the last decade [1]. Despite much success, this approach also proved to have certain drawbacks and faces several challenges on the way to its widespread adoption. In the meantime, there is a growing consensus that a third strategy, based on the integration of tissue spheroids with conventional solid scaffolds, could be a potential optimal solution [2].
A representative example of the third strategy in tissue engineering is a recently reported lockyball construct - a tissue spheroid encaged within a highly porous microscaffold [3]. Lockyballs support bottom-up modular tissue assembly, since the size and the porosity of microscaffolds promote spheroid fusion, while providing high initial cell density. At the same time the microscaffolds material can be varied independently of the tissue spheroid, enabling adjustment of the mechanical properties of the construct and its degradation profile. In addition, microscaffolds can be designed to contain functional elements, such as hooks allowing interlocking with neighboring microscaffolds. Two-photon polymerization (2PP) technique, based on localized crosslinking of photopolymers induced by femtosecond laser pulses, was used by our group to produce first lockyballs [4]. Due to high spatial resolution provided by 2PP, this technique is most perspective for fabrication of microscaffolds with size is on the order of the spheroid diameter (100-500 µm).
In this contribution we review the recent reports supporting manifestation of such development. The main principles, distinguishing elements and current challenges of this emerging third strategy in tissue engineering will be discussed.

tissue engineering

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