Servicenavigation

Detailseite

Zurück

Projekt Druckansicht

Eine neue Generation von 3D-Scaffolds für Patienten-spezifische Therapien in orthopädischen Anwendungen

Fachliche Zuordnung Biomaterialien
Förderung Förderung von 2018 bis 2022
Projektkennung Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 392224788
 
Erstellungsjahr 2022

Zusammenfassung der Projektergebnisse

3D plotting is an additive manufacturing technique based on extrusion of pasty materials through a nozzle, producing three-dimensional constructs of computer aided-designed internal and external geometry. Current research using this technique to fabricate constructs for tissue regeneration have been focused on improving their abilities to stimulate bone and vascular tissue formation, e.g. by tailoring their inner and outer porosity, which also allows fabrication of patient-specific bone implants. Another challenge is the problem of implant-related infections. This project aimed to respond to these challenges by developing modular system as tailorable “tool-box” for fabrication of patient-specific bone implants. Our strategy was to combine novel therapeutic bioceramics and pasty materials into composites, processible by 3D plotting. Therapeutic effect of established materials was obtained by modifications with bioactive metal ions, considering antibacterial properties of zinc- and cerium ions (Zn2+ and Ce3+), promoting of bone formation by magnesium (Mg2+), chromium (Cr3+) and strontium (Sr2+) and reported positive effects of copper (Cu2+) on vascularization. All of these ions were used for modification of mesoporous bioactive glasses (MBG), which are silica-based materials specific for their channel structure, allowing them to act as drug and growth factor delivery systems. In addition, MBG have high degradation rates, making them favorable for integration into less degradable materials like calcium phosphate cements (CPC). In addition, Sr2+ was integrated in hydroxyapatite (Sr-HAp). Modification of MBG originally containing 15% of calcium (Ca) with different amounts of Zn (up to 15%) did not impair the pore-channel structure. However, the release of Zn2+ was lower than Ca2+ when it was present in the MBG at the same initial amount. Different effects of these two ions were also observed when different MBG were integrated into already established alginate (alg)-based blends. Composites containing more Zn were less viscous and less applicable for extrusion printing of porous constructs, but they were stable over time in cell culture conditions, while the ones containing only Ca were falling apart after one week. To overcome this limitation, plotting in core/shell manner was applied, providing coaxial strands containing CaMBG-composite in the core and stable material in the shell. The release of ions over time from the core was confirmed with alg-based blend or CPC in the shell. Concentrations of Zn2+ effective against bacteria were lower than the released ones from MBG, meaning that the release of this ion should be additionally tailored. However, the absence of toxicity of release products from Zn-containing composite scaffolds towards bone-like cells, with concentrations of Zn2+ reported earlier to be harmful, showed promising perspective of these composites to be used for fabrication of bone implants with antibacterial potential. We demonstrated an antibacterial potential of cerium ions as well, at concentrations without any negative effects on cell viability. Surprisingly, when we used the same protocol to integrate this ion into MBG network the pore channel structure of the glass was disturbed. On the other side, incorporation of Mg2+ maintained the channel structure. MgMBG degraded slower in the composite, showing a burst release of Mg2+ only at very first time points. The same was observed with the release of Cu2+ from Cu-modified MBG in composites. In addition to the modified MBG, Cu-based silica-material Cuprovaite (Cup) was provided by our collaboration partner in China. This material has more crystalline structure in comparison to MBG and therefore it degrades slower. Due to lower release of Cu2+, Cup-composites were not toxic for human cells. In addition, their release products significantly increased mineralization, showing high potential for bone formation. We confirmed as well the potential of Cr3+ to stimulate bone-like cells, but its incorporation in the MBG revealed an important problem, as during synthesis partly toxic and carcinogenic Cr(VI) compounds were formed. We could decrease the amount of these phases by changing certain reactional conditions, but this will require more investigation. This is the second trivalent ion (besides Ce3+) showing problematic synthesis of MBG, while divalent ions did not show any effect on the resulting structure of the glass. When Sr was integrated in MBG, it was not possible to obtain plottable composites with alg-based blend due to resulting very high viscosity. However, this MBG was successfully combined with CPC, showing the possibility to tailor the release of therapeutic ions and degradation behavior. Furthermore, it was possible to load this MBG with protein and growth factors and to measure their release from 3D plotted composite constructs over time. In addition, we successfully synthesized and characterized SrHAp nanoparticles, which could be integrated in an alg-based blend, obtaining plottable composites. Released concentrations of Sr2+ were in the range found to be favorable for formation of bone tissue. In addition, release products significantly increased mineralization. During conducting our project, we observed an important effect of the MBG on common evaluation analyses with cells. MBG particles show the same fluorescent signal in green channel, after using commercial live/dead assay for observation of metabolically active and dead cells in 3D plotted MBG-containing composite constructs. We suggested a solution to overcome this limitation by prelabelling the cells prior plotting, and then staining only metabolically active cells. In addition, MBG particles and/or released MBG-products interfere with quantitative evaluation of cell number and cell differentiation. Some of these effects were ion-dependent, showing an importance of systematic and detailed characterization of each modified MBG to avoid misleading results. Our findings show very promising potential of this biomaterial “tool box” for fabrication of patient-specific boneimplants with tailorable therapeutic properties.

Projektbezogene Publikationen (Auswahl)

 
 

Zusatzinformationen

© 2026 DFG Kontakt / Impressum / Datenschutz

Textvergrößerung und Kontrastanpassung