Geometrical confinement controls cell, ECM and vascular network alignment during the morphogenesis of 3D bioengineered human connective tissues.

Autor: Casale C; Interdisciplinary Research Centre on Biomaterials (CRIB), University of Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy. Electronic address: costantino.casale@unina.it., Imparato G; Center for Advanced Biomaterials for Health Care@CRIB Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci n. 53, 80125 Napoli, Italy., Mazio C; Center for Advanced Biomaterials for Health Care@CRIB Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci n. 53, 80125 Napoli, Italy., Netti PA; Interdisciplinary Research Centre on Biomaterials (CRIB), University of Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy; Center for Advanced Biomaterials for Health Care@CRIB Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci n. 53, 80125 Napoli, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy., Urciuolo F; Interdisciplinary Research Centre on Biomaterials (CRIB), University of Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy; Department of Chemical, Materials and Industrial Production Engineering (DICMAPI), University of Napoli Federico II, P.le Tecchio 80, 80125 Napoli, Italy.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2021 Sep 01; Vol. 131, pp. 341-354. Date of Electronic Publication: 2021 Jun 16.
DOI: 10.1016/j.actbio.2021.06.022
Abstrakt: Engineered tissues featuring aligned ECM possess superior regenerative capabilities for the healing of damaged aligned tissues. The morphofunctional integration in the host's injury site improves if the aligned ECM elicits the unidirectional growth of vascular network. In this work we used a bottom-up tissue engineering strategy to produce endogenous and highly aligned human connective tissues with the final aim to trigger the unidirectional growth of capillary-like structures. Engineered microtissues, previously developed by our group, were casted in molds featured by different aspect ratio (AR) to obtain final centimeter-sized macrotissues differently shaped. By varying the AR from 1 to 50 we were able to vary the final shape of the macrotissues, from square to wire. We demonstrated that by increasing the AR of the maturation space hosting the microtissues, it was possible to control the alignment of the neo-synthesized ECM. The geometrical confinement conditions at AR = 50, indeed, promoted the unidirectional growth and assembly of the collagen network. The wire-shaped tissues were characterized by parallel arrangement of the collagen fiber bundles, higher persistence length and speed of migrating cells and superior mechanical properties than the square-shaped macrotissues. Interestingly, the aligned collagen fibers elicited the unidirectional growth of capillary-like structures. STATEMENT OF SIGNIFICANCE: Alignment of preexisting extracellular matrices by using mechanical cues modulating cell traction, has been widely described. Here, we show a new method to align de novo synthesized extracellular matrix components in bioengineered connective tissues obtained by means of a bottom-up tissue engineering approach. Building blocks are cast in maturation chambers, having different aspect ratios, in which the in vitro morphogenesis process takes place. High aspect ratio chambers (corresponding to wire-shaped tissues) triggered spontaneous alignment of collagenous network affecting cell polarization, migration and tensile properties of the tissue as well. Aligned ECM provided a contact guidance for the formation of highly polarized capillary-like network suggesting an in vivo possible application to trigger fast angiogenesis and perfusion in damaged aligned tissues.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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