Nerve guidance conduits (NGCs) have been drawing considerable attention as an aid to promote regeneration of injured axons across damaged peripheral nerves. Ideally, NGCs should include physical and topographic axon guidance cues embedded as part of their composition. Over the past decades, much progress has been made in the development of NGCs that promote directional axonal regrowth so as to repair severed nerves. This paper briefly reviews the recent designs and fabrication techniques of NGCs for peripheral nerve regeneration. Studies associated with versatile design and preparation of NGCs fabricated with either conventional or rapid prototyping (RP) techniques have been examined and reviewed. The effect of topographic features of the filler material as well as porous structure of NGCs on axonal regeneration has also been examined from the previous studies. While such strategies as macroscale channels, lumen size, groove geometry, use of hydrogel/matrix, and unidirectional freeze-dried surface are seen to promote nerve regeneration, shortcomings such as axonal dispersion and wrong target reinnervation still remain unsolved. On this basis, future research directions are identified and discussed.
Rapid progress in tissue engineering research in past decades has opened up vast possibilities to tackle the challenges of generating tissues or organs that mimic native structures. The success of tissue engineered constructs largely depends on the incorporation of a stable vascular network that eventually anastomoses with the host vasculature to support the various biological functions of embedded cells. In recent years, significant progress has been achieved with respect to extrusion, laser, micro-molding, and electrospinning-based techniques that allow the fabrication of any geometry in a layer-by-layer fashion. Moreover, decellularized matrix, self-assembled structures, and cell sheets have been explored to replace the biopolymers needed for scaffold fabrication. While the techniques have evolved to create specific tissues or organs with outstanding geometric precision, formation of interconnected, functional, and perfused vascular networks remains a challenge. This article briefly reviews recent progress in 3D fabrication approaches used to fabricate vascular networks with incorporated cells, angiogenic factors, proteins, and/or peptides. The influence of the fabricated network on blood vessel formation, and the various features, merits, and shortcomings of the various fabrication techniques are discussed and summarized.
Extrusion-based bioprinting of hydrogel scaffolds is challenging due to printing-related issues, such as the lack of capability to precisely print or deposit hydrogels onto three-dimensional (3D) scaffolds as designed. Printability is an index to measure the difference between the designed and fabricated scaffold in the printing process, which, however, is still under-explored. While studies have been reported on printing hydrogel scaffolds from one or more hydrogels, there is limited knowledge on the printability of hydrogels and their printing processes. This paper presented our study on the printability of 3D printed hydrogel scaffolds, with a focus on identifying the influence of hydrogel composition and printing parameters/conditions on printability. Using the hydrogels synthesized from pure alginate or alginate with gelatin and methyl-cellulose, we examined their flow behavior and mechanical properties, as well as their influence on printability. To characterize the printability, we examined the pore size, strand diameter, and other dimensions of the printed scaffolds. We then evaluated the printability in terms of pore/strand/angular/printability and irregularity. Our results revealed that the printability could be affected by a number of factors and among them, the most important were those related to the hydrogel composition and printing parameters. This study also presented a framework to evaluate alginate hydrogel printability in a systematic manner, which can be adopted and used in the studies of other hydrogels for bioprinting.
Tissue regeneration with scaffolds has proven promising for the repair of damaged tissues or organs. Dispensing-based printing techniques for scaffold fabrication have drawn considerable attention due to their ability to create complex structures layer-by-layer. When employing such printing techniques, the flow rate of the biomaterial dispensed from the needle tip is critical for creating the intended scaffold structure. The flow rate can be affected by a number of variables including the material flow behavior, temperature, needle geometry, and dispensing pressure. As such, model equations can play a vital role in the prediction and control of the flow rate of the material dispensed, thus facilitating optimal scaffold fabrication. This paper presents the development of a model to represent the flow rate of medium viscosity alginate dispensed for the purpose of scaffold fabrication, by taking into account the shear and slip flow from a tapered needle. Because the fluid flow behavior affects the flow rate, model equations were also developed from regression of experimental data to represent the flow behavior of alginate. The predictions from both the flow behavior equation and flow rate model show close agreement with experimental results. For varying needle diameters and temperatures, the slip effect occurring at the needle wall has a significant effect on the flow rate of alginate during scaffold fabrication.
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