4D Biofabrication of Mechanically Stable Tubular Constructs Using Shape Morphing Porous Bilayers for Vascularization Application

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Trujillo-Miranda, Mairon ; Apsite, Indra ; Rodríguez Agudo, Jose A. ; Constante Ibarra, Gissela Katherine ; Ionov, Leonid:
4D Biofabrication of Mechanically Stable Tubular Constructs Using Shape Morphing Porous Bilayers for Vascularization Application.
In: Macromolecular Bioscience. Bd. 23 (2023) Heft 1 . - 2200320.
ISSN 1616-5195
DOI: https://doi.org/10.1002/mabi.202200320

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Abstract

This study reports fabrication of highly porous electrospun self-folding bilayers, which fold into tubular structures with excellent mechanical stability, allowing them to be easily manipulated and handled. We fabricated and compared two kinds of bilayers based on FDI-approved biocompatible and biodegradable soft (PCL, polycaprolactone) and hard (PHB, poly-hydroxybutyrate) thermoplastic polymers. Multi-scroll structures with tunable diameter in aqueous media were obtained after the shape transformation of the bilayer, where PCL-based bilayer rolled longitudinally and PHB-based one rolled transversely with respect to fiber direction. A combination of higher elastic modulus and transverse orientation of fibers with respect to rolling direction allowed precise temporal control of shape transformation of PHB-bilayer – stress produced by swollen methacrylated hyaluronic acid (HA-MA) did not relax with time and folding was not affected by the fact that bilayer was fixed in unfolded state in cell culture medium for more than 1 h. This property of PHB-bilayer allowed cell culturing without negative effect on its shape transformation ability. Moreover, PHB-based tubular structure demonstrated superior mechanical stability compared to PCL-based ones and did not collapse during manipulations that happened to PCL-based one. Additionally, PHB/HA-MA bilayers showed superior biocompatibility, degradability, and long-term stability compared to PCL/HA-MA. After 14 days of cultivation, our vascular grafts showed high stability in cultivation, and between 50–70% of the multi-scroll area was fully covered. All these make bilayer of transversely aligned hard thermoplastic polymer fibers (such as PHB) and swelling hydrophilic polymer fibers (such as HA-MA) more suitable for the fabrication of blood vessel replacement in comparison to widely used PCL-based bilayers.