Speaker
Description
Introduction: Ionic medicine is an approach that proposes the use of therapeutic ions to stimulate cell growth, reduce inflammation, combat oxidative stress, and promote tissue regeneration1. Biofabrication offers a solution for addressing muscle loss in situations where the human body cannot heal itself effectively2. To enhance muscle cell growth by ionic stimulation, this study established a novel bioink system comprising alginate-dialdehyde–gelatin (ADA-GEL) hydrogel, a biocompatible and printable hydrogel widely used in biofabrication3, and ion-releasing bioactive glass (BG) nanoparticles.
Methods: Mesoporous bioactive glass nanoparticles (MBGNs) of calcium silicate composition, selectively doped with boron and cerium, were synthesized, and their physical and chemical properties were characterized. Composite inks were formulated by incorporating 0.1–1% (w/v) MBGNs into 2.5%ADA-5%GEL (w/v). The swelling and degradation behavior, mechanical properties and printability of the hydrogels were investigated. Furthermore, C2C12 myoblast cells were bioprinted and cell viability and morphology were evaluated post-printing.
Results and Discussion: MBGNs were synthesized in three categories: without dopant, with a single doping element, and with dual (Ce, B) dopants. MBGNs were spherical with diameters of 90-180 nm and demonstrated a gradual release of ions into the aqueous environment over time. Dopant ions affected the release rate of silicon ions.
Incorporation of MBGNs into ADA-GEL narrowed the available printing window due to accelerated gelation induced by the presence of particles and ions. This effect was particularly noticeable in inks containing 1% (w/v) nanoparticles. Nevertheless, printability assessments showed that all formulations exhibited good processability and printability with well-defined printed structures.
The swelling and degradation of hydrogels showed a similar trend over the incubation period for all compositions. ADA-GEL containing dual-doped MBGNs displayed long-term stability compared to pure ADA-GEL and ADA-GEL containing single-doped MBGNs. The impact of the addition of MBGNs on the compressive modulus was also dependent on ion type and particle concentration. However, the impact diminished after 24 hours of sample incubation.
Finally, bioprinting was conducted with C2C12 cells encapsulated in the hydrogels. Metabolic activity of bioprinted cells increased over a 14-day incubation period, with 0.1 and 1% (w/v) undoped MBGNs to the greatest extent, followed by single-doped nanoparticles. A uniform distribution of cells with elongated morphology was observed. Quantitative analysis of cell alignment demonstrated the highest alignment with 1% (w/v) undoped and single-doped MBGNs.
Conclusions: All ADA-GEL-BG inks, together with optimized printing platforms, enhanced myoblast cell growth and alignment in bioprinted constructs, particularly with 1% (w/v) single-doped MBGNs. The results highlight the potential of the system for muscle tissue engineering strategies and represent an example of application of the emerging field of ionic medicine.
References:
1. Lu, H.-H. et al. Acta Biomater 190, 1–23 (2024).
2. Ostrovidov, S. et al. Small 15, 1–14 (2019).
3. Sarker, B. et al. J Mater Chem B 2, 1470–1482 (2014).
Acknowledgments: This work is funded by the German Research Foundation (DFG), project number 326998133 – SFB/TRR225 (subproject B03). Hana Kaňková acknowledges funding from the Slovak Recovery Plan under grant agreement No. 09I01-03-V04-00040/2024/VA.
85410407688
