Fiber spinning for tissue engineering applications

  • Faserspinnen für Tissue Engineering Anwendungen

Omidinia Anarkoli, Abdolrahman; De Laporte, Laura (Thesis advisor); Wessling, Matthias (Thesis advisor)

Aachen (2020)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2020


Aiming to mimic the natural extracellular matrix (ECM) structure of tissues to facilitate the growth and maturation of 3D functional tissues in and ex vivo, many “top-down” and “bottom-up” tissue engineering techniques have been employed over the past decades to fabricate 3D scaffolds. Among different scaffold types, fibrous constructs have always been of great interest due to their structure emulating the native fibrous ECM, and the possibility of the controlling fiber length, diameter, and organization to meet specific scaffold requirements for diverse tissue engineering applications. Compared to conventional fiber spinning techniques, such as electrospinning, Solvent Assisted Spinning (SAS) developed here enables the control of alignment, inter-fiber distance (IFD), and surface topography of fibers in an easier and more reliable manner. It is observed that the surface topography of SAS fibers, induced by phase separation, can alter cell mechanotransduction by changing cell cytoskeleton elongation and, potentially, nucleus pore opening. Further applications of SAS fibers demonstrate how nerve cell orientation, number of branching and maximum neurite length are affected by fiber surface topography at various IFDs. Moving from the developed 2.5D systems towards 3D constructs, a hybrid hydrogel (called Anisogel) is developed, which can be applied as an injectable therapeutic material, featuring both injectability and unidirectionality after injection. To do this, magneto responsive short fibers doped with iron oxide super-para-magnetic nanoparticles are developed and mixed with an injectable hydrogel. Following injection in the presence of a small external magnetic field, the short fibers orient in the direction of the magnetic field, while the surrounding hydrogel is enzymatically crosslinked to fix the position of the short fibers. Such types of hydrogels are an important new class of materials that can be applied in a minimally invasive manner and provide anisotropic guiding structures, important properties of therapeutic materials for soft tissues with linear ECM architecture, like the spinal cord. Compared to conventional hydrogels with isotropic structures, Anisogels with oriented short fibers show nerve cells linear growth and signal propagation in the direction fibers. Besides their tissue regeneration applications when used as scaffolds, fibers can also be used as medical devices for wound dressing and/or barrier for post injury tissue adhesion. By combining the properties of hydrogels and fibers, hydrogel fibers aiming to fully mimic the ECM structure and composition are presented. Using an optimized electrospinning process, and in combination with liquid star-shaped polyethylene glycol functionalized with epoxy and amine end groups, hydrogel fibers with variable properties (i.e. swelling rate, diameter) are made. These can be used for the fabrication of multilayered 3D constructs, each layer potentially possessing different chemical, physical, or mechanical properties in a gradient fashion, with great potential for their application as wound dressings. Overall, by altering fiber properties at different scales (i.e. nano, micro, macro), unique functions, such as injectability, remote orientation, surface topography, and water swellability, have been achieved, which alone or in combination can be used for various tissue engineering applications.