Abstract
In this paper, we describe the application of the 4D biofabrication approach for the fabrication of artificial nerve graft. Bilayer scaffolds consisting of uniaxially aligned polycaprolactone-poly(glycerol sebacate) (PCL-PGS) and randomly aligned methacrylated hyaluronic acid (HA-MA) fibers were fabricated using electrospinning and further used for the culture of PC-12 neuron cells. Tubular structures form instantly after immersion of fibrous bilayer in an aqueous buffer and the diameter of obtained tubes can be controlled by changing bilayer parameters such as the thickness of each layer, overall bilayer thickness, and medium counterion concentration. Designed scaffolds showed a self-folded scroll-like structure with high stability after four weeks of real-time degradation. The significance of this research is in the fabrication of tuneable tubular nerve guide conduits that can simplify the current existing clinical treatment of neural injuries.
Highlights
More than a million people each year are affected by peripheral nerve injuries, which can lead to the reduction of motor function, sensory perception, and in severe cases even death [1, 2]
We show that biodegradable electrospun bilayer made of polycaprolactone-poly(glycerol sebacate) (PCL-PGS) and methacrylated hyaluronic acid (HA-MA) forms stable scroll-like tubular structures where the inner layer with aligned fibers provides the contact guidance to cells to form unidirectional neurites outgrowth
The top layer is formed by uniaxial aligned PCL-PGS fibers; the bottom layer is formed by disordered HA-MA fibers
Summary
More than a million people each year are affected by peripheral nerve injuries, which can lead to the reduction of motor function, sensory perception, and in severe cases even death [1, 2]. Autografts are used in clinical practice to oppose nerve ends. This technique has shown promising outcomes for nerve injury repair, it requires suitable donor material [7, 8]. Tissue engineering approach and usage of implantable hollow nerve guide conduits (NGCs) have been introduced as an attractive alternative; until now, NGCs have been used only for small defect repair [9]. 3D bioprinting of cell-laden hydrogels is one of the most used and promising methods for the fabrication of NGCs in the latest years. This approach allows homogenous cell distribution [21]. There are several limitations of 3D printing such as the low resolution of printing of a tubular structure [22], narrow NGCs wall thickness to ensure waste product and nutrient permeability [23], and high shear forces during direct printing of NGCs [24]
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