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

Abstract

This study reports the 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. Two kinds of bilayers based on biocompatible and biodegradable soft (PCL, polycaprolactone) and hard (PHB, poly‐hydroxybutyrate) thermoplastic polymers have been fabricated and compared. Multi‐scroll structures with tunable diameter are obtained after the shape transformation of the bilayer in aqueous media, where PCL‐based bilayer rolled longitudinally and PHB‐based one rolled transversely with respect to the 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) do not relax with time and folding is not affected by the fact that bilayer is fixed in unfolded state in cell culture medium for more than 1 h. This property of PHB‐bilayer allowed cell culturing without a negative effect on its shape transformation ability. Moreover, PHB‐based tubular structure demonstrated superior mechanical stability compared to PCL‐based ones and do 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.

Design-encoded dual shape-morphing and shape-memory in 4D printed polymer parts toward cellularized vascular grafts

“…Manufacturing vascular grafts of clinically relevant dimensions remains a key biofabrication challenge in the biomedical field, as it demands small diameters and relatively larger lengths. 39 Electrospun bilayers, 40 molded polymer tubes, 41 and 4D printed hydrogels [42][43][44][45] present significant limitations as vascular grafts due to incomplete and unstable shape deformation, complex chemical reactions and short-term patency, and poor mechanical strength, respectively. These limitations are further accentuated if the tubes need to be pre-seeded with cells prior to implantation, as none of the conventional processing techniques can realize cell-laden tubes with high shape fidelity and stability.…”

4D Printing for Vascular Tissue Engineering: Progress and Challenges

“…PHB‐based layer folded transversely while the PCL‐based folded longitudinally, further, PHB‐based bilayer was mechanically strong and resisted any collapse during manipulation. [ 108 ]…”

Active Materials for Functional Origami

“…As mentioned previously, hydrogels have been widely used for biomedical applications. Self-rolled tubes for vascularization [233] as well as numerous grippers [30,161,162,234] for drug delivery or cell removal (biopsy) in surgical applications have been demonstrated with hydrogels. Notably, Gracias and coworkers [161,162] have created origami microgrippers by incorporating stiff polymer panels with a thermoresponsive hydrogel substrate, where the stiffness of the panels granted additional functionality to the gripper, such as the possibility of cell excision.…”