Mesoporous bioactive glass nanoparticles (MBGNs) have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn), zinc (Zn), and copper (Cu) ions have already shown promising pro‐osteogenic properties. Therefore, the concentration‐dependent impact of MBGNs (composition in mol%: 70 SiO₂, 30 CaO) and MBGNs containing 5 mol% of either Mn, Zn, or Cu (composition in mol%: 70 SiO₂, 25 CaO, 5 MnO/ZnO/CuO) on the viability and osteogenic differentiation of human marrow‐derived mesenchymal stromal cells (BMSCs) was assessed in this study. Mn‐doped MBGNs (5Mn‐MBGNs) showed a small “therapeutic window” with a dose‐dependent negative impact on cell viability but increasing pro‐osteogenic features alongside increasing Mn concentrations. Due to a constant release of Zn, 5Zn‐MBGNs showed good cytocompatibility and upregulated the expression of genes encoding for relevant members of the osseous extracellular matrix during the later stages of cultivation. In contrast to all other groups, BMSC viability increased with increasing concentration of Cu‐doped MBGNs (5Cu‐MBGNs). Furthermore, 5Cu‐MBGNs induced an increase in alkaline phosphatase activity. In conclusion, doping with Mn, Zn, or Cu can enhance the biological properties of MBGNs in different ways for their potential use in bone regeneration approaches.

Patient-derived mesenchymal stromal cells (MSCs) play a key role in bone tissue engineering. Various donor-specific factors were identified causing significant variability in the biological properties of MSCs impairing quality of data and inter-study comparability. These limitations might be overcome by pooling cells of different donors. However, the effects of pooling on osteogenic differentiation, proliferation and vitality remain unknown and have, therefore, been evaluated in this study. MSCs of 10 donors were cultivated and differentiated into osteogenic lineage individually and in a pooled setting, containing MSCs of each donor in equal parts. Proliferation was evaluated in expansion (assessment of generation time) and differentiation (quantification of dsDNA content) conditions. Vitality was visualized by a fluorescence-microscopy-based live/dead assay. Osteogenic differentiation was assessed by quantification of alkaline phosphatase (ALP) activity and extracellular calcium deposition. Compared to the individual setting, generation time of pooled MSCs was shorter and proliferation was increased during differentiation with significantly lower variances. Calcium deposition was comparable, while variances were significantly higher in the individual setting. ALP activity showed high variance in both groups, but increased comparably during the incubation period. In conclusion, MSC pooling helps to compensate donor-dependent variability and does not negatively influence MSC vitality, proliferation and osteogenic differentiation.

Standard treatment for bone defects is the biological reconstruction using autologous bone—a therapeutical approach that suffers from limitations such as the restricted amount of bone available for harvesting and the necessity for an additional intervention that is potentially followed by donor-site complications. Therefore, synthetic bone substitutes have been developed in order to reduce or even replace the usage of autologous bone as grafting material. This structured review focuses on the question whether calcium phosphates (CaPs) and bioactive glasses (BGs), both established bone substitute materials, show improved properties when combined in CaP/BG composites. It therefore summarizes the most recent experimental data in order to provide a better understanding of the biological properties in general and the osteogenic properties in particular of CaP/BG composite bone substitute materials. As a result, BGs seem to be beneficial for the osteogenic differentiation of precursor cell populations in-vitro when added to CaPs. Furthermore, the presence of BG supports integration of CaP/BG composites into bone in-vivo and enhances bone formation under certain circumstances.

Growth factors and mesenchymal stem cells (MSC) support consolidation of bone defects. Bone Morphogenetic Protein-7 (BMP-7) has been used clinically and experimentally, but the outcomes remain controversial. Increased systemic expression of Insulin-like Growth Factor-1 (IGF-1) significantly correlates with successful regeneration of bone healing disorders, making IGF-1 a promising alternative to BMP-7. There is no experimental data comparing the osteoinductive potential of IGF-1 and BMP-7. Therefore, in this study, the influence of IGF-1 and BMP-7 in different concentrations on the osteogenic differentiation of two human MSC-subtypes, isolated from reaming debris (RMSC) and iliac crest bone marrow (BMSC) has been assessed. A more sensitive reaction of BMSC towards stimulation with IGF-1 in concentrations of 400–800 ng/mL was found, leading to a significantly higher degree of osteogenic differentiation compared to stimulation with BMP-7. RMSC react more sensitively to stimulation with BMP-7 compared to BMSC. Lower concentrations of IGF-1 were necessary to significantly increase osteogenic differentiation of RMSC and BMSC compared to BMP-7. Therefore, IGF-1 should be considered as a valuable option to improve osteogenic differentiation of MSC and merits further experimental consideration. The MSC subtype and method of differentiation factor application also have to be considered, as they affect the outcome of osteogenic differentiation.

Since the amount of autologous bone for the treatment of bone defects is limited and harvesting might cause complications, synthetic bone substitutes such as the popular β-tricalcium phosphate (β-TCP) based Vitoss have been developed as an alternative grafting material. β-TCPs exhibit osteoconductive properties, however material-initiated stimulation of osteogenic differentiation is limited. These limitations might be overcome by addition of 45S5 bioactive glass (BG) particles. This study aims to analyze the influence of BG particles in Vitoss BA (20 wt% BG particles with a size of 90–150 μm) on osteogenic properties, cell vitality and cell proliferation in direct comparison to Vitoss by evaluation of the underlying cellular mechanisms. For that purpose, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stem cells (MSC) and underwent osteogenic differentiation in-vitro for up to 42 days. Cell vitality, proliferation, and osteogenic differentiation were monitored by quantitative gene expression analysis, determination of alkaline phosphatase activity, PrestoBlue cell viability assay, dsDNA quantification, and a fluorescence-microscopy-based live/dead-assay. It was demonstrated that BG particles decrease cell proliferation but do not have a negative impact on cell vitality. Especially the early stages of osteogenic differentiation were significantly improved in the presence of BG particles, resulting in earlier maturation of the MSC towards osteoblasts. Since most of the stimulatory effects induced by BG particles took place initially, particles exhibiting another surface-area-to-volume ratio should be considered in order to provide long-lasting stimulation.

Mesoporous bioactive glass nanoparticles (MBGNs) based on the SiO₂–P₂O₅–CaO system have demonstrated promising properties for the local delivery of therapeutically active ions with the aim to improve their osteogenic properties. Manganese (Mn) has been identified as a candidate ion for local application in bone tissue engineering applications. It remains unknown how SiO₂–P₂O₅–CaO‐based MBGNs influence human bone marrow‐derived mesenchymal stromal cells (BMSCs) in terms of viability, proliferation, and differentiation and how these features can be modified by the addition of Mn to the MBGNs' composition. Therefore, in this study, MBGNs (composition in mol%: 50 SiO₂, 40 CaO, 10 P₂O₅) and its Mn‐doped derivate 5Mn‐MBGNs (composition in mol%: 50 SiO₂, 35 CaO, 10 P₂O₅, 5 MnO) were applied to a culture of BMSCs in two different concentrations. With increasing concentration, 5Mn‐MBGNs supported osteogenic differentiation and enhanced the upregulation of genes encoding for extracellular matrix proteins but also negatively influenced cell viability and proliferation. When applied in lower concentrations, MBGNs showed not only viability‐ and growth‐enhancing effects but also significant pro‐osteogenic features—however, these positive properties deteriorated with increasing concentration. Two major conclusions can be drawn from this study: (a) supplementation with Mn enhances the osteogenic properties of MBGNs in a dose‐dependent manner and (b) MBGNs constitute an attractive vector for therapeutically active ions since it exhibits an intrinsic pro‐osteogenic potential that can be improved and/or modified by incorporation of therapeutically active ions. Future studies should focus on the evaluation of further candidate ions that are known to influence osteogenic differentiation positively.