Glycerylphytate compounds with tunable ion affinity and osteogenic properties

Abstract

Phytic acid (PA) is a natural-occurring antioxidant, which plays an important role in many biological processes. PA is recognized as a potent inhibitor of lipid peroxidation because of its high affinity to multivalent cations, and it can play a role in osteogenic processes. However, its powerful chelating capacity is controversial because it can lead to a severe reduction of mineral availability in the organism. For this reason, compounds with beneficial biological properties of PA, but a modular ion binding capacity, are of high interest. In this work, we report the synthesis and physicochemical characterization of two hydroxylic derivatives of PA, named glycerylphytates (GPhy), through a condensation reaction of PA with glycerol (G). Both derivatives present antioxidant properties, measured by ferrozine/FeCl 2 method and chelating activity with calcium ions depending on the content of glyceryl groups incorporated. Besides, the hydroxylic modification not only modulates the ion binding affinity of derivatives but also improves their cytocompatibility in human bone marrow mesenchymal cells (MSCs). Furthermore, GPhy derivatives display osteogenic properties, confirmed by COL1A and ALPL expression depending on composition. These positive features convert GPhy compounds into potent alternatives for those skeletal diseases treatments where PA is tentatively applied.

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

“…54 In addition, the organic segment incorporated into the phytic acid structure favours interaction with cells. 32 This second crosslinking step contributed to maintained shape fidelity and positively influenced swelling and long-term stability of the scaffolds (Fig. 4b).…”

“…The G 1 Phy crosslinker was synthesized in our lab as published elsewhere. 32 The dispensing tips were purchased from VIEWEG GmbH Dosier-und Mischtechnik (Kranzberg, Germany) and dispensing Optimum® cartridges from Nordson (Erkrath, Germany).…”

“…G 1 Phy plays a key role since it provides robust networks and avoids the necessity of neutralization and washing steps. 32 The as-obtained 3D printed structures exhibit good printability, adequate mechanical properties and long-term stability. Thus, our approach involves a two-step crosslinking process that combined UV photopolymerization of GelMA followed by postprinting ionic crosslinking with G 1 Phy.…”

“…23 Therefore, the development of successful strategies to overcome current limitations in the 3D printing field using hydrogels is demanded. The present work proposes the use of the crosslinker glycerylphytate (G 1 Phy) developed by our group 32 in the fabrication of dual crosslinked 3D scaffolds using a low concentrated (<10 wt%) ink of GelMA/ chitosan. Although other studies have been focused on the combination of gelatin with chitosan because of their ability to form together polyelectrolyte complexes, 15,24,25,33 the blend ink composed of GelMA/chitosan has not be reported so far.…”

“…This approach improves resolution and shape fidelity without the necessity of using sacrificial polymers or template agents, which are common techniques applied to water-based ink solutions. 11,37,38 This approach and the incorporation of a novel crosslinker such as G 1 Phy for subsequent ionic gelation not only provides appropriate processability properties to the scaffolds but also bioactive properties 32 in comparison to traditional alginate-Ca 2+ ionic crosslinking systems frequently applied in dual-step 3D printing technology.…”