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Towards the challenges of 3D bioprinting for salivary glands (SG) regeneration: Complex SG scaffolds with imprinted vasculature

par Siminska-Stanny, Julia ;Hachemi, Feza F.H.;Nizioł, Martyna;Podstawczyk, Daria;Delporte, Christine ;Shavandi, Amin
Référence (2-3.12.2022: Antwerp), Belgian Society of Tissue Engineering, BSTE
Publication Publié, 2022

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Résumé :

Bioinks and biomaterial inks that can be transformed into genuine 3D constructs, employing 3D printing technology signify a step towards personalized treatments and tissue engineering. Currently, many studies focused on regenerative medicine strategies also exemplify the need for vascularization within the obtained in vitro structures as it is crucial to maintain cell survival and therefore hasten the regeneration process. To date, only a handful of materials have been investigated in terms of their utilization for salivary gland (SG) tissue engineering while creating an artificial SG vasculature system still remains one of the biggest hurdles.To confront these challenges within our work we utilize a 3D extrusion bioprinting technique to successfully obtain SG scaffolds of superior shape fidelity while preserving the inherent biocompatibility of the ink components. Additionally, as vascularization is abundant for cell survival, we propose a 3D fabrication approaches that could address both: the fabrication of artificial SG matrix and vessel scaffolds.By combining the excellent properties of gelatin, hyaluronic acid (HA) and methylcellulose (MC) with extrusion-based direct printing technology, we developed a novel 3D-printable hydrogel (Gel-HA-MC). Thoughtfully optimizing the polymers share in the formulation, we printed stable 3D scaffolds presenting high accuracy and stability, both during and after printing, at room and body temperature. A peculiarity of Gel-HA-MC materials lies in their ability for dual-stage crosslinking due to the methacrylation (GelMA) and phenolation (HA-Tyr) of polymers' backbones. Upon the first crosslinking stage we obtained shear-thinning inks for convenient 3D printing at relatively low polymer concentrations. In the second stage the photopolymerization reactions, triggered by visible light in a presence of a cell-friendly photoinitiation system (riboflavin and sodium persulfate) resulted in a stable hydrogel printout. The high-water content and swelling capacity (550 %) of Gel-HA-MC hydrogels combined with their ECM-like characteristics, richness in RGD peptides and cytocompatibility towards SG cells proved their suitability for biological applications including engineering of SG models.To 3D print perfusable channels mimicking blood vessels, we used a novel coaxial printing technique. In this manner simultaneous extrusion of the Alg - based ink (as the outer layer) with the fugitive polymer-Pluronic F127® (the inner side of the nozzle) allowed the hydrogel to form a core-shell tube (inner diameter ~360 µm, outer ~1000 µm). After structure strengthening by Ca2+ crosslinking and leaching the polymer from the core part, we obtained perfusable, flexible tubes showing great potency to act as small blood vessels or fine capillaries. The vascular grafts of this size are challenging to fabricate, however, are predominant in every tissue and organ of our body. Due to that, coaxial printing can be a promising way to introduce vascular structures into a small size engineered tissue.Considering the aspect of vascularization in artificial tissue grafts we hope to bring the current strategies a step closer to finding feasible tissue replacements. Additionally, our work may help to tackle the problem of artificial SG tissue fabrication and help to obtain in vitro models for determining SG malfunction’ underpinnings and screening treatments. It can be a cornerstone for a new method of developing vascularized tissue replacements in clinically relevant dimensions.