Macromolecular crowding transforms regenerative medicine by enabling the accelerated development of functional and truly three-dimensional cell assembled micro tissues. (August 2022)

• Record Type: Journal Article
• 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.
• Is Part Of: Biomaterials. Volume 287(2022)
• Publication Date: 2022-08
• Subjects: Temperature-responsive polymers -- Electrospinning -- Macromolecular crowding -- Excluded volume effect -- In vitro organogenesis; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121674
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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/cm 2 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. Graphical abstract: 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. Image 1