Enhancing 3D bioprinting functionalities using ion-releasing bioactive glass nanoparticle-containing bioinks

Abstract

3D bioprinting offers a promising approach to fabricate customized scaffolds for tissue engineering and in vitro models [1]. One approach being investigated to improve bioinks for 3D bioprinting is the use of composite bioinks which incorporate ion releasing bioreactive (nano)particles. In this context, research at the FAU Institute of Biomaterials in Erlangen has focused on hydrogels based on alginate dialdehyde-gelatin (ADA-GEL) incorporating ion-releasing bioactive glass (BG) nanoparticles which can be designed to improve printability, mechanical properties, degradation behaviour and biological performance of the 3D bioprinted constructs. In this presentation we will describe the synthesis of ADA via oxidation of alginate [2], and the fabrication of mesoporous BG nanoparticles (MBGNs) via evaporation-induced self-assembly [3] and microemulsion-assisted [4] sol-gel methods. It will be shown that differences in particle size, surface area, and porosity of MBGNs influence the extent of ion release and the gelation of the inks. Different biologically active ions investigated are Cu, Zn, Mg, B, Li, and Ce. Ibn some cases, released ions acted as in situ crosslinking agents, leading to tunable gelation behavior and a defined processing window. With optimized printing parameters, the composite inks produced continuous filaments and three-dimensional structures with shape fidelity. Bioprinting studies were conducted using NIH/3T3 fibroblasts and C2C12 myoblasts [5] in order to establish the functionalities provided by the incorporated ion releasing MBGNs. Local ion release in the hydrogel can lead to significant effects on cellular response indicating potential advantages of utilizing biologically active ions as signaling agents instead of organic molecules or growth factors. For example, incorporating 0.1% w/v MBGNs in cell-laden constructs led to enhanced metabolic activity, highlighting the beneficial role of ion-releasing particles. This work demonstrated that ADA-GEL based composite hydrogels with ion-releasing particles provide reliable printability, tunable properties, and improved cellular responses, supporting their potential as an ionic medicine strategy for bioprinting applications. The work is funded by German Research Foundation, CRC/SFB225 B03.

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[4] K. Zheng, A.R. Boccaccini, Adv. Colloid Interface Sci. 249 (2017) 363–373.
[5] H. H. Lu, et al., Biomaterials Advances 172 (2025) 214233.