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Increased levels of reactive oxygen species (ROS) favor adipogenic over osteogenic differentiation in human bone-marrow derived mesenchymal stromal cells (BMSCs). Therefore, biomaterials containing ROS-suppressing elements such as Cerium (Ce) have been introduced to cell-based bone-tissue-engineering (BTE) approaches. This study was conducted to assess the efficacy of Ce-doped mesoporous bioactive glass nanoparticles (MBGNs) in reducing ROS levels and subsequently inhibiting the adipogenic differentiation of BMSCs. To this end, BMSCs were cultivated in adipogenesis inducing medium (AIM) and exposed to ions released from Ce-free MBGNs (composition in mol%: 86SiO 2 -14CaO), Low-Ce-MBGNs (composition in mol%: 86.6SiO 2 -12.1CaO-1.3CeO 2 ) and High-Ce-MBGNs (composition in mol%: 86.0SiO 2 -11.8CaO-2.2CeO 2 ). The influence of the different MBGNs on the expression of adipogenic and ROS-scavenging genes was assessed as well as their influence on lipid formation and the physical presence of ROS. Ce-MBGNs significantly reduced lipid production and the expression of adipogenic marker genes when compared to BMSCs cultivated in the presence of MBGNs or AIM alone. Furthermore, ROS levels were decreased by Ce-MBGNs alongside an upregulation of the expression of genes encoding for ROS-scavenging enzymes. Ce-MBGNs have proven their antioxidative potential. Mediated by the reduction of ROS, the undesired differentiation of BMSCs towards adipogenic lineage within BTE applications has been effectively suppressed. Ce-MBGNs target differentiation pathways in BMSCs precisely and therefore constitute an attractive biomaterial in the field of ion-based BTE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The 0106-B1-bioactive glass (BG) composition (in wt %: 37.5 SiO 2 , 22.6 CaO, 5.9 Na 2 O, 4.0 P 2 O 5 , 12.0 K 2 O, 5.5 MgO, and 12.5 B 2 O 3 ) has demonstrated favorable processing properties and promising bone regeneration potential. The present study aimed to evaluate the biological effects of the incorporation of highly pro-angiogenic copper (Cu) in 0106-B1-BG in vitro using human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as its in vivo potential for bone regeneration. CuO was added to 0106-B1-BG in exchange for CaO, resulting in Cu-doped BG compositions containing 1.0, 2.5 and 5.0 wt % CuO (composition in wt %: 37.5 SiO 2 , 21.6/ 20.1/17.6 CaO, 5.9 Na 2 O, 4.0 P 2 O 5 , 12.0 K 2 O, 5.5 MgO, 12.5 B 2 O 3 , and 1.0/ 2.5/ 5.0 CuO). In vitro, the BGs' impact on the viability, proliferation, and growth patterns of BMSCs was evaluated. Analyses of protein secretion, matrix formation, and gene expression were used for the assessment of the BGs' influence on BMSCs regarding osteogenic differentiation and angiogenic stimulation. The presence of Cu improved cytocompatibility, osteogenic differentiation, and angiogenic response when compared with unmodified 0106-B1-BG in vitro. In vivo, a critical-size femoral defect in rats was filled with scaffolds made from BGs. Bone regeneration was evaluated by micro-computed tomography. Histological analysis was performed to assess bone maturation and angiogenesis. In vivo effects regarding defect closure, presence of osteoclastic cells or vascular structures in the defect were not significantly changed by the addition of Cu compared with undoped 0106-B1-BG scaffolds. Hence, while the in vitro properties of the 0106-B1-BG were significantly improved by the incorporation of Cu, further evaluation of the BG composition is necessary to transfer these effects to an in vivo setting., (© 2024 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Despite their long history of application in orthopedics, the osteogenic and angiogenic properties as well as the cytocompatibility and protein adsorption of the 45S5- (in wt%: 45.0 SiO 2 , 24.5 Na 2 O, 24.5 CaO, 6.0 P 2 O 5 ) and S53P4- (in wt%: 53.0 SiO 2 , 23.0 Na 2 O, 20.0 CaO, 4.0 P 2 O 5 ) bioactive glass (BG) compositions have not yet been directly compared in one and the same experimental setting. In this study, the influence of morphologically equal granules of both BGs on proliferation, viability, osteogenic differentiation and angiogenic response of human bone-marrow-derived mesenchymal stromal cells (BMSCs) was assessed. Furthermore, their impact on vascular tube formation and adsorption of relevant proteins was evaluated. Both BGs showed excellent cytocompatibility and stimulated osteogenic differentiation of BMSCs. The 45S5-BG showed enhanced stimulation of bone morphogenic protein 2 (BMP2) gene expression and protein production compared to S53P4-BG. While gene expression and protein production of vascular endothelial growth factor (VEGF) were stimulated, both BGs had only limited influence on tubular network formation. 45S5-BG adsorbed a higher portion of proteins, namely BMP2 and VEGF, on its surface. In conclusion, both BGs show favorable properties with slight advantages for 45S5-BG. Since protein adsorption on BG surfaces is important for their biological performance, the composition of the proteome formed by osteogenic cells cultured on BGs should be analyzed in order to gain a deeper understanding of the mechanisms that are responsible for BG-mediated stimulation of osteogenic differentiation., (Creative Commons Attribution license.)

An ICIE16-bioactive glass (BG) composition (in mol%: 49.5 SiO 2 , 6.6 Na 2 O, 36.3 CaO, 1.1 P 2 O 5 , and 6.6 K 2 O) has demonstrated excellent in vitro cytocompatibility when cultured with human bone marrow-derived mesenchymal stromal cells (BMSCs). However, its impact on the development of an osseous extracellular matrix (ECM) is limited. Since zinc (Zn) is known to enhance ECM formation and maturation, two ICIE16-BG-based Zn-supplemented BG compositions, namely 1.5 Zn-BG and 3Zn-BG (in mol%: 49.5 SiO 2 , 6.6 Na 2 O, 34.8/33.3 CaO, 1.1 P 2 O 5 , 6.6 K 2 O, and 1.5/3.0 ZnO) were developed, and their influence on BMSC viability, osteogenic differentiation, and ECM formation was assessed. Compared to ICIE16-BG, the Zn-doped BGs showed improved cytocompatibility and significantly enhanced osteogenic differentiation. The expression level of the osteopontin gene was significantly higher in the presence of Zn-doped BGs. A larger increase in collagen production was observed when the BMSCs were exposed to the Zn-doped BGs compared to that of the ICIE16-BG. The calcification of the ECM was increased by all the BG compositions; however, calcification was significantly enhanced by the Zn-doped BGs in the early stages of cultivation. Zn constitutes an attractive addition to ICIE16-BG, since it improves its ability to build and calcify an ECM. Future studies should assess whether these positive properties remain in an in vivo environment.

Besides its favorable biological properties, the release of sodium (Na) from the well-known 45S5-bioactive glass (BG) composition (in mol%: 46.1, SiO 2 , 24.5 CaO, 24.5 Na 2 O, 6.0 P 2 O 5 ) can hamper its cytocompatibility. In this study, particles of Na-reduced variants of 45S5-BG were produced in exchange for CaO and P 2 O 5 via the sol-gel-route resulting in Na contents of 75%, 50%, 25% or 0% of the original composition. The release of ions from the BGs as well as their impact on the cell environment (pH values), viability and osteogenic differentiation (activity of alkaline phosphatase (ALP)), the expression of osteopontin and osteocalcin in human bone-marrow-derived mesenchymal stromal cells in correlation to the Na-content and ion release of the BGs was assessed. The release of Na-ions increased with increasing Na-content in the BGs. With decreasing Na content, the viability of cells incubated with the BGs increased. The Na-reduced BGs showed elevated ALP activity and a pro-osteogenic stimulation with accelerated osteopontin induction and a pronounced upregulation of osteocalcin. In conclusion, the reduction in Na-content enhances the cytocompatibility and improves the osteogenic properties of 45S5-BG, making the Na-reduced variants of 45S5-BG promising candidates for further experimental consideration.

Since the introduction of the 45S5-bioactive glass (BG), numerous new BG compositions have been developed. Compared to the 45S5-BG, 1393-BG shows favorable processing properties due to its low crystallization tendency and the 1393-BG-based borosilicate 0106-B1-BG exhibits improved angiogenic properties due to its boron content. Despite their close (chemical) relationship, the biological properties of the mentioned BG composition have not yet been comparatively examined. In this study, the effects of the BGs on proliferation, viability, osteogenic differentiation, and angiogenic factor production of human bone marrow-derived mesenchymal stromal cells were assessed. Scaffolds made of the BGs were introduced in a critical-sized femur defect model in rats in order to analyze their impact on bone defect regeneration. In vitro, 1393-BG and 0106-B1-BG outperformed 45S5-BG with regard to cell proliferation and viability. 1393-BG enhanced osteogenic differentiation; 0106-B1-BG promoted angiogenic factor production. In vivo, 0106-B1-BG and 45S5-BG outperformed 1393-BG in terms of angiogenic and osteoclastic response resulting in improved bone regeneration. In conclusion, the biological properties of BGs can be significantly modified by tuning their composition. Demonstrating favorable processing properties and an equally strong in vivo bone regeneration potential as 45S5-BG, 0106-B1-BG qualifies as a basis to incorporate other bioactive ions to improve its biological properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bilateral defects (diameter 8 mm) in the medial tibial head of senile, osteopenic female sheep (n = 48; 9.63 ± 0.10 years; mean ± SEM) were treated with hydroxyapatite (HA)/beta-tricalcium phosphate (β-TCP)/dicalcium phosphate dihydrate (DCPD; brushite) cylinders coated with BMP-2 (25 or 250 micrograms) or growth differentiation factor (GDF)-5 (125 or 1250 micrograms; left side); cylinders without BMP served as controls (right side). Three, 6, and 9 months post-operation (n = 6 each group), bone structure and formation were analyzed in vivo by X-ray and ex vivo by osteodensitometry, histomorphometry, and micro-computed tomography (micro-CT) at 3 and 9 months. Semi-quantitative X-ray evaluation showed significantly increasing bone densities around all implant cylinders over time. High-dose BMP-2-coated cylinders (3 and 9 months) and low-dose GDF-5-coated cylinders (3 and 6 months) demonstrated significantly higher densities than controls (dose-dependent for BMP-2 at 3 months). This was confirmed by osteodensitometry at 9 months for high-dose BMP-2-coated cylinders (and selected GDF-5 groups), and was again dose-dependent for BMP-2. Osteoinduction by BMP-2 was most pronounced in the adjacent bone marrow (dynamic histomorphometry/micro-CT). BMP-2 (and partially GDF-5) significantly increased the bone formation in the vicinity of HA/TCP/DCPD cylinders used to fill tibial bone defects in senile osteopenic sheep and may be suitable for surgical therapy of critical size, non-load-bearing bone defects in cases of failed tibial head fracture or defect healing., (© 2023. The Author(s).)

Medical nutrients obtained from plants have been used in traditional medicine since ancient times, owning to the protective and therapeutic properties of plant extracts and products. Glycyrrhizic acid is one of those that, apart from its therapeutic effect, may contribute to stronger bones, inhibiting bone resorption and improving the bone structure and biomechanical strength. In the present study, we investigated the effect of a bioactive glass (BG) addition to the structure-property relationships of supramolecular assemblies formed by glycyrrhizic acid (GA) and its monoammonium salt (MSGA). FTIR spectra of supramolecular assemblies evidenced an interaction between BG components and hydroxyl groups of MSGA and GA. Moreover, it was revealed that BG components may interact and bond to the carboxyl groups of MSGA. In order to assess their biological effects, BG, MSGA, and their supramolecular assemblies were introduced to a culture of human bone-marrow-derived mesenchymal stromal cells (BMSCs). Both the BG and MSGA had positive influence on BMSC growth, viability, and osteogenic differentiation-these positive effects were most pronounced when BG1d-BG and MSGA were introduced together into cell culture in the form of MSGA:BG assemblies. In conclusion, MSGA:BG assemblies revealed a promising potential as a candidate material intended for application in bone defect reconstruction and bone tissue engineering approaches.