Macromolecular crowding transforms regenerative medicine by enabling the accelerated development of functional and truly three-dimensional cell assembled micro tissues

• Published in: Biomaterials Vol. 287; p. 121674
• Main Authors: De Pieri, Andrea, Korntner, Stefanie H., Capella-Monsonis, Hector, Tsiapalis, Dimitrios, Kostjuk, Sergei V., Churbanov, Semyon, Timashev, Peter, Gorelov, Alexander, Rochev, Yuri, Zeugolis, Dimitrios I.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.08.2022
• Subjects: Electrospinning; Excluded volume effect; In vitro organogenesis; Macromolecular crowding; Temperature-responsive polymers; Macromolecular crowding; Electrospinning; In vitro organogenesis; Excluded volume effect; Temperature-responsive polymers
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2022.121674

Scaffold-free in vitro organogenesis exploits the innate ability of cells to synthesise and deposit their own extracellular matrix to fabricate tissue-like assemblies. Unfortunately, cell-assembled tissue engineered concepts require prolonged ex vivo culture periods of very high cell numbers for the development of a borderline three-dimensional implantable device, which are associated with phenotypic drift and high manufacturing costs, thus, hindering their clinical translation and commercialisation. Herein, we report the accelerated (10 days) development of a truly three-dimensional (338.1 ± 42.9 μm) scaffold-free tissue equivalent that promotes fast wound healing and induces formation of neotissue composed of mature collagen fibres, using human adipose derived stem cells seeded at only 50,000 cells/cm2 on an poly (N-isopropylacrylamide-co-N-tert-butylacrylamide (PNIPAM86-NTBA14) temperature-responsive electrospun scaffold and grown under macromolecular crowding conditions (50 μg/ml carrageenan). Our data pave the path for a new era in scaffold-free regenerative medicine. Human adipose derived stem cells seeded on temperature-responsive electrospun scaffolds under macromolecular crowding conditions allowed the accelerated development of truly three-dimensional cell assembled micro tissues, the functionality of which was demonstrated in a wound healing model. [Display omitted]