TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) A1 - Fan, Lu A1 - Körte, Fabian A1 - Rudt, Alexander A1 - Jung, Ole A1 - Burkhardt, Claus A1 - Barbeck, Mike A1 - Xiong, Xin T1 - Encapsulated vaterite-calcite CaCO3 particles loaded with Mg2+ and Cu2+ ions with sustained release promoting osteogenesis and angiogenesis JF - Frontiers in Bioengineering and Biotechnology N2 - Bioactive cations, including calcium, copper and magnesium, have shown the potential to become the alternative to protein growth factor-based therapeutics for bone healing. Ion substitutions are less costly, more stable, and more effective at low concentrations. Although they have been shown to be effective in providing bone grafts with more biological functions, the precise control of ion release kinetics is still a challenge. Moreover, the synergistic effect of three or more metal ions on bone regeneration has rarely been studied. In this study, vaterite-calcite CaCO3 particles were loaded with copper (Cu2+) and magnesium (Mg2+). The polyelectrolyte multilayer (PEM) was deposited on CaCuMg-CO3 particles via layer-by-layer technique to further improve the stability and biocompatibility of the particles and to enable controlled release of multiple metal ions. The PEM coated microcapsules were successfully combined with collagen at the outmost layer, providing a further stimulating microenvironment for bone regeneration. The in vitro release studies showed remarkably stable release of Cu2+ in 2 months without initial burst release. Mg2+ was released in relatively low concentration in the first 7 days. Cell culture studies showed that CaCuMg-PEM-Col microcapsules stimulated cell proliferation, extracellular maturation and mineralization more effectively than blank control and other microcapsules without collagen adsorption (Ca-PEM, CaCu-PEM, CaMg-PEM, CaCuMg-PEM). In addition, the CaCuMg-PEM-Col microcapsules showed positive effects on osteogenesis and angiogenesis in gene expression studies. The results indicate that such a functional and controllable delivery system of multiple bioactive ions might be a safer, simpler and more efficient alternative of protein growth factor-based therapeutics for bone regeneration. It also provides an effective method for functionalizing bone grafts for bone tissue engineering. KW - bioactive cations KW - bone regeneration KW - polyelectrolyte multilayer KW - collagen KW - vaterite-calcite Y1 - 2022 UN - https://nbn-resolving.org/urn:nbn:de:bsz:rt2-opus4-40819 SN - 2296-4185 SS - 2296-4185 U6 - https://doi.org/10.3389/fbioe.2022.983988 DO - https://doi.org/10.3389/fbioe.2022.983988 VL - 10 SP - 1 EP - 16 S1 - 16 PB - Frontiers Media CY - Lausanne ER -