Evaluation of the clinical effectiveness of bioactive glass (S53P4) in the treatment of non-unions of the tibia and femur: study protocol of a randomized controlled non-inferiority trial

Background: Treatment of non-union remains challenging and often necessitates augmentation of the resulting defect with an autologous bone graft (ABG). ABG is limited in quantity and its harvesting incurs an additional surgical intervention leaving the risk for associated complications and morbidities. Therefore, artificial bone graft substitutes that might replace autologous bone are needed. S53P4-type bioactive glass (BaG) is a promising material which might be used as bone graft substitute due to its osteostimulative, conductive and antimicrobial properties. In this study, we plan to examine the clinical effectiveness of BaG as a bone graft substitute in Masquelet therapy in comparison with present standard Masquelet therapy using an ABG with tricalciumphosphate to fill the bone defect. Methods/design: This randomized controlled, clinical non-inferiority trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University. Patients who suffer from tibial or femoral non-unions with a segmental bone defect of 2–5 cm and who are receiving Masquelet treatment will be included in the study. The resulting bone defect will either be filled with autologous bone and tricalciumphosphate (control group, N = 25) or BaG (S53P4) (study group, N = 25). Subsequent to operative therapy, all patients will receive the same standardized follow-up procedures. The primary endpoint of the study is union achieved 1year after surgery. Discussion: The results from the current study will help evaluate the clinical effectiveness of this promising biomaterial in non-union therapy. In addition, this randomized trial will help to identify potential benefits and limitations regarding the use of BaG in Masquelet therapy. Data from the study will increase the knowledge about BaG as a bone graft substitute as well as identify patients possibly benefiting from Masquelet therapy using BaG and those who are more likely to fail, thereby improving the quality of non-union treatment. Trial registration: German Clinical Trials Register (DRKS), ID: DRKS00013882 . Registered on 22 January 2018

Vorschlag für ein Kompetenzprofil für Studienberater/-innen an Hochschulen in der Allgemeinen Studienberatung

In der Arbeit wird ein Kompetenzprofil für Berater der Allgemeinen Studienberatung an Hochschulen entwickelt. Das Kompetenzmodell wird mittels einem systemtheoretischen Hintergrund hergeleitet. Dabei werden verschiedenen Ebenen (Beratungsprozess, Ratsuchende, Beratende, Organisation und Gesellschaft) berücksichtigt. Auf das Systemische Kontextmodell nach Schiersmann et al. (2008) wird Bezug genommen. Die Entwicklung der Allgemeinen Studienberatung an Hochschulen und deren Aufgaben werden dargestellt. Studienberatungsstellen sind mittlerweile an den Hochschulen fest institutionalisierte Einrichtungen und ein Teil der Bildungs- und Berufsberatung. Für die Studienberatung existiert aufgrund der breit gefächerten Vielfalt bislang weder eine klare allgemeingültige Tätigkeitsbeschreibung noch eine eindeutige Aufgabentrennung zwischen unterschiedlichen Akteuren im Bereich der Studienberatung innerhalb einer Hochschule. Die Hochschulen sind in der Ausgestaltung ihres Beratungsangebotes autonom. Dies hat zur Folge, dass die Beratung in der Regel von verschiedenen Einrichtungen innerhalb der Hochschule wahrgenommen wird und deren Verortung sowie die inhaltlich-fachliche Anbindung innerhalb der Hochschulen unterschiedlich ist. Studienberatung, als ein Teil der Bildungs- und Berufsberatung, definiert sich aus theoretischen Grundlagen professioneller Beratung und den hochschulspezifischen Rahmenbedingungen. Daher ist es für die Akzeptanz eines Kompetenzprofils für Studienberater unerlässlich, dieses theorie- und praxisbegründet zu entwickeln. Unter den Gesichtspunkten Professionalität und Qualität ergeben sich folgende Fragen: Wer berät wann, wie und mit welcher Kompetenz und mit welchen Methoden zu welchen Themen? Welche Ansprüche darf ein Ratsuchender an die Beratenden haben? Nach welchen Grundsätzen erfolgt professionelle Beratung? Welche Methoden sind angemessen? Was müssen Beratende wissen und können? Welche Kompetenzen sollen Beratende haben bzw. sich aneignen

Preconditioning of Bioactive Glasses before Introduction to Static Cell Culture: What Is Really Necessary?

Due to their high bioreactivity, the in-vitro analysis of bioactive glasses (BGs) can be challenging when it comes to maintaining a physiological pH. To improve BG biocompatibility, a heterogenic spectrum of preconditioning approaches, such as “passivation” of the BGs by incubation in cell culture medium, are used but have never been directly compared. In this study, the effect of passivation periods of up to 72 h on pH alkalization and viability of human bone marrow-derived mesenchymal stromal cells was evaluated to determine a time-efficient passivation protocol using granules based on the 45S5-BG composition (in wt%: 45.0 SiO2, 24.5 Na2O, 24.5 CaO, 6.0 P2O5) in different concentrations. pH alkalization was most reduced after passivation of 24 h. Cell viability continuously improved with increasing passivation time being significantly higher after passivation of at least 24 h compared to non-passivated 45S5-BG and the necessary passivation time increased with increasing BG concentrations. In this setting, a passivation period of 24 h presented as an effective approach to provide a biocompatible cell culture setting. In conclusion, before introduction of BGs in cell culture, different passivation periods should be evaluated in order to meet the respective experimental settings, e.g., by following the experimental protocols used in this study

NÓS X A GENTE: UMA ANÁLISE DOS PRONOMES NAS CRÔNICAS DE LUIS FERNANDO VERÍSSIMO

Esta pesquisa compara as ocorrências dos pronomes nós e a gente na língua escrita e analisa os usos do segundo quanto à referência semântica, tendo como amostra seis obras de Luis Fernando Veríssimo. Observou-se que o uso do pronome nós predomina sobre o pronome a gente. Quanto à análise das referências semânticas, concluiu-se que, entre referências específica e genérica, há a predominância de uso do pronome a gente de forma genérica, característica herdada do substantivo gente.This study compares the occurrences of the pronouns “nós” and “a gente” in written language and analyzes the uses of the latter in terms of semantic reference, considering as a sample six texts by Luis Fernando Veríssimo. It was observed that the use of the pronoun “nós” prevails over the pronoun “a gente”. The analysis of semantic references shows that, between specific and generic references, the use of “a gente” prevails in generic form, a characteristic inherited from the noun “gente”

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed

Primary osteoblasts, osteoblast precursor cells or osteoblast‐like cell lines: Which human cell types are (most) suitable for characterizing 45S5‐bioactive glass?

Abstract The question how bioactive glasses (BGs) influence the viability and osteogenic differentiation of human osteogenic cells has already been addressed by several studies. However, a literature review revealed great differences in the type of cells used for these experiments. Primary human osteoblasts (hOBs) represent the desired standard, but possess the limitation of patient variability and time‐consuming isolation protocols. Therefore, several alternative cell types have been used including primary mesenchymal stromal cells (BMSCs) and the “osteoblast‐like” cell lines MG‐63, Saos‐2, HOS, and U2OS. The aim of our study was the identification of the cell type most suitable for tissue engineering projects involving BGs by comparative analysis of cell viability and osteogenic differentiation in response to crystallized 45S5‐BG. We observed that hOBs, BMSCs, and MG‐63 cells were resistant to 45S5‐BG induced cytotoxicity, while the viability of Saos‐2, HOS, and U2OS cells was significantly reduced. In addition, we detected alkaline phosphatase activity, except in U2OS cells, that increased upon 45S5‐BG cocultivation, demonstrating the induction of osteogenic differentiation. Our data and the fact that the donor‐dependent variations can be avoided when using MG‐63 cells suggest that these are a promising alternative to primary cells and remain an important cell line for future BG related studies

Biological Properties of Calcium Phosphate Bioactive Glass Composite Bone Substitutes: Current Experimental Evidence

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

Insights into ionic medicine: Cerium reduces the presence of reactive oxygen species and favors osteogenic over adipogenic differentiation in human mesenchymal stromal cells

The guided application of metallic ions in bone tissue engineering (BTE) has recently gained popularity being described as one important example of ionic medicine (IM). BTE aims to enhance osteogenic differentiation of precursor cells like bone-marrow-derived mesenchymal stromal cells (BMSCs) and, by that, regenerate bone tissue. BMSCs however can also differentiate into adipogenic lineage. It is known that elevated levels of reactive oxygen species (ROS) stimulate BMSC towards (undesired) adipogenic differentiation. One ion, that is particularly interesting for application in IM-guided BTE is cerium (Ce) since it acts as a self-regenerating ROS-scavenger and has already been successfully incorporated in biomaterials. Ce has demonstrated pro-osteogenic, anti-adipogenic and anti-oxidative effects before, however, so far, there is no direct comparative study available that analyzes these effects on human BMSCs in one and the same setting. Therefore, in this study, the influence of Ce nitrate (CeN) on the expression of osteogenic, adipogenic and ROS-scavenging genes in BMSCs was evaluated as well as its impact on formation of an osseous extracellular matrix (ECM), lipid formation and physical ROS presence. The presence of CeN improved BMSCs viability, enhanced proliferation, and reduced ROS-levels. Furthermore, CeN suppressed adipogenesis while osteogenic differentiation and the formation and maturation of the ECM were enhanced. The presence of CeN reduced the physical presence of ROS and the gene expression patterns shifted towards an anti-oxidant profile. Ce therefore constitutes an attractive ion for application in IM-guided BTE. Further research is necessary to clarify the biological mechanisms and pathways that are involved in the Ce-mediated modulation of BMSC differentiation

Micro-Computed-Tomography-Guided Analysis of In Vitro Structural Modifications in Two Types of 45S5 Bioactive Glass Based Scaffolds

Three-dimensional 45S5 bioactive glass (BG)-based scaffolds are being investigated for bone regeneration. Besides structural properties, controlled time-dependent alteration of scaffold morphology is crucial to achieve optimal scaffold characteristics for successful bone repair. There is no in vitro evidence concerning the dependence between structural characteristics and dissolution behavior of 45S5 BG-based scaffolds of different morphology. In this study, the dissolution behavior of scaffolds fabricated by the foam replica method using polyurethane foam (Group A) and maritime sponge Spongia Agaricina (Group B) as sacrificial templates was analyzed by micro-computed-tomography (µCT). The scaffolds were immersed in Dulbecco’s Modified Eagle Medium for 56 days under static cell culture conditions and underwent µCT-analysis initially, and after 7, 14, and 56 days. Group A showed high porosity (91%) and trabecular structure formed by macro-pores (average diameter 692 µm ± 72 µm). Group-B-scaffolds were less porous (51%), revealing an optimal pore size distribution within the window of 110–500 µm pore size diameter, combined with superior mechanical stability. Both groups showed similar structural alteration upon immersion. Surface area and scaffold volume increased whilst density decreased, reflecting initial dissolution followed by hydroxycarbonate-apatite-layer-formation on the scaffold surfaces. In vitro- and/or in vivo-testing of cell-seeded BG-scaffolds used in this study should be performed to evaluate the BG-scaffolds’ time-dependent osteogenic properties in relation to the measured in vitro structural changes