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Glycerylphytate as an ionic crosslinker for 3D printing of multi-layered scaffolds with improved shape fidelity and biological features

2020, Mora-Boza, A., Włodarczyk-Biegun, M.K., Del Campo, A., Vázquez-Lasa, B., Román, J.S.

The fabrication of intricate and long-term stable 3D polymeric scaffolds by a 3D printing technique is still a challenge. In the biomedical field, hydrogel materials are very frequently used because of their excellent biocompatibility and biodegradability, however the improvement of their processability and mechanical properties is still required. This paper reports the fabrication of dual crosslinked 3D scaffolds using a low concentrated (<10 wt%) ink of gelatin methacryloyl (GelMA)/chitosan and a novel crosslinking agent, glycerylphytate (G1Phy) to overcome the current limitations in the 3D printing field using hydrogels. The applied methodology consisted of a first ultraviolet light (UV) photopolymerization followed by a post-printing ionic crosslinking treatment with G1Phy. This crosslinker provides a robust framework and avoids the necessity of neutralization with strong bases. The blend ink showed shear-thinning behavior and excellent printability in the form of a straight and homogeneous filament. UV curing was undertaken simultaneously to 3D deposition, which enhanced precision and shape fidelity (resolution ≈150 μm), and prevented the collapse of the subsequent printed layers (up to 28 layers). In the second step, the novel G1Phy ionic crosslinker agent provided swelling and long term stability properties to the 3D scaffolds. The multi-layered printed scaffolds were mechanically stable under physiological conditions for at least one month. Preliminary in vitro assays using L929 fibroblasts showed very promising results in terms of adhesion, spreading, and proliferation in comparison to other phosphate-based traditional crosslinkers (i.e. TPP). We envision that the proposed combination of the blend ink and 3D printing approach can have widespread applications in the regeneration of soft tissues.

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Laminin Adsorption and Adhesion of Neurons and Glial Cells on Carbon Implanted Titania Nanotube Scaffolds for Neural Implant Applications

2022, Frenzel, Jan, Kupferer, Astrid, Zink, Mareike, Mayr, Stefan G.

Interfacing neurons persistently to conductive matter constitutes one of the key challenges when designing brain-machine interfaces such as neuroelectrodes or retinal implants. Novel materials approaches that prevent occurrence of loss of long-term adhesion, rejection reactions, and glial scarring are highly desirable. Ion doped titania nanotube scaffolds are a promising material to fulfill all these requirements while revealing sufficient electrical conductivity, and are scrutinized in the present study regarding their neuron–material interface. Adsorption of laminin, an essential extracellular matrix protein of the brain, is comprehensively analyzed. The implantation-dependent decline in laminin adsorption is revealed by employing surface characteristics such as nanotube diameter, (Formula presented.) -potential, and surface free energy. Moreover, the viability of U87-MG glial cells and SH-SY5Y neurons after one and four days are investigated, as well as the material’s cytotoxicity. The higher conductivity related to carbon implantation does not affect the viability of neurons, although it impedes glial cell proliferation. This gives rise to novel titania nanotube based implant materials with long-term stability, and could reduce undesirable glial scarring.