Novel bone tissue engineering strategy based on the interplay of ion-doped bioactive glass nanoparticles in biopolymer-based hydrogels with electrical stimulation

• Applicant: Privatdozentin Dr. Vera Hintze
• Subject Area: Biomaterials
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567400032

Nanocomposites from biopolymer-derived hydrogels and ion-doped, mesoporous bioactive glass nanoparticles (MBGNs) are excellent candidates for bone tissue engineering (TE) applications. This is, since therapeutic ions increase the osteogenic effects of MBGNs, further promoting MBGN-related benefits like improved bone cell responses, mechanical properties, bioactivity and well-defined degradations profiles. In parallel, electric field (EF) stimulation has gained significant attention in enhancing osteogenic differentiation in vitro and in vivo. Hence, its inclusion during bone TE is a logical approach to attain advanced vital bone TE constructs in terms of maturation stage, mechanical properties and cross talk with further relevant bone cells. However, there is a shortage of studies exploring possible synergistic effect of ion-doped MBGN-containing 3D composites and EF stimulation for bone TE, in particular with respect to more physiological EF parameters and limited side effects (e.g. magnetic fields). A further aspect often neglected are bone cell interactions and cellular cross talk of the matured TE constructs in a co-culture setting with human monocytes (hMCs). We address this knowledge gap by integrating the interplay of these (bio)chemical and (bio)physical cues into a novel TE approach. To this end, biopolymer/Sr2+- und Cu2+-doped MBGN nanocomposites, with different MBGN composition and concentration will be established and characterized. A deeper understanding of bone cell dynamics in this multi-factorial microenvironment will be derived by an in-depth analysis of the cellular response of human bone marrow-derived mesenchymal stem cells (hBMSCs), comparing effects related to ion dissolution products versus direct cellular contact. This will be done in the additional context of different pulsatile, transformer-like coupling-based EF stimulation regimes for elucidating possible synergetic effects, also considering physiological field strength and frequency parameters. The so derived mature TE constructs will be assessed for their impact on hMC differentiation to osteoclasts (OC) as well as for OC-feedback to osteoblasts in a co-culture setting to mimic bone cell interactions and early remodeling events in vivo. Knowledge generated will enable defining the most effective parameter sets for controlling physico-chemical properties (e.g. bioactivity, elasticity, degradation, ion release) and for promoting bone-cell responses and cellular crosstalk. Finally, our approach will identify the best-suited microenvironmental parameters and thus a functional bone TE strategy, promoting the osteogenesis of hBMSCs, while enabling a balanced osteoclastogenesis. In perspective, this strategy might be translated to patient-specific in vitro cell culture models and in vivo applications for enhanced bone regeneration, fostering earlier osseointegration and recovery of bone-like biochemical performance and functionality, e.g. in cranial applications.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr.-Ing. Aldo Boccaccini