Trivalent chromium incorporated in a crystalline calcium phosphate matrix accelerates materials degradation and bone formation in vivo.

Unlabelled: Remodeling of calcium phosphate bone cements is a crucial prerequisite for their application in the treatment of large bone defects. In the present study trivalent chromium ions were incorporated into a brushite forming calcium phosphate cement in two concentrations (10 and 50 mmol/mol β-tricalcium phosphate) and implanted into a femoral defect in rats for 3 and 6 month, non-modified brushite was used as reference. Based on our previous in vitro findings indicating both an enhanced osteoclastic activity and cytocompatibility towards osteoprogenitor cells we hypothesized a higher in vivo remodeling rate of the Cr doped cements compared to the reference.

Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.

Aims/hypothesis: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes.

Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression.

A 4D view on insulin secretory granule turnover in the β-cell.

Insulin secretory granule (SG) turnover consists of several highly regulated processes allowing for proper β-cell function and insulin secretion. Besides the spatial distribution of insulin SGs, their age has great impact on the likelihood of their secretion and their behaviour within the β-cell. While quantitative measurements performed decades ago demonstrated the preferential secretion of young insulin, new experimental approaches aim to investigate insulin ageing at the granular level.

Green bioprinting: extrusion-based fabrication of plant cell-laden biopolymer hydrogel scaffolds.

Plant cell cultures produce active agents for pharmaceuticals, food and cosmetics. However, up to now process control for plant cell suspension cultures is challenging. A positive impact of cell immobilization, such as encapsulation in hydrogel beads, on secondary metabolites production has been reported for several plant species.

Osteoclastic differentiation and resorption is modulated by bioactive metal ions Co2+, Cu2+ and Cr3+ incorporated into calcium phosphate bone cements.

Biologically active metal ions in low doses have the potential to accelerate bone defect healing. For successful remodelling the interaction of bone graft materials with both bone-forming osteoblasts and bone resorbing osteoclasts is crucial. In the present study brushite forming calcium phosphate cements (CPC) were doped with Co2+, Cu2+ and Cr3+ and the influence of these materials on osteoclast differentiation and activity was examined.

Development of a clay based bioink for 3D cell printing for skeletal application.

Three-dimensional printing of cell-laden hydrogels has evolved as a promising approach on the route to patient-specific or complex tissue-engineered constructs. However, it is still challenging to print structures with both, high shape fidelity and cell vitality. Herein, we used a synthetic nanosilicate clay, called Laponite, to build up scaffolds utilising the extrusion-based method 3D plotting.

Data on TOF-SIMS analysis of Cu, Co and Cr doped calcium phosphate cements.

This article contains data of time of flight secondary ion mass spectrometry (TOF-SIMS) analysis of brushite-forming calcium phosphate cements doped with biologically active metal ions. This data are related to the research article "Cu, Co and Cr doping of a calcium phosphate cement influences materials properties and response of human mesenchymal stromal cells" (Schamel et al., 2017) [1].

Central Growth Factor Loaded Depots in Bone Tissue Engineering Scaffolds for Enhanced Cell Attraction.

Tissue engineering, the application of stem and progenitor cells in combination with an engineered extracellular matrix, is a promising strategy for bone regeneration. However, its success is limited by the lack of vascularization after implantation. The concept of in situ tissue engineering envisages the recruitment of cells necessary for tissue regeneration from the host environment foregoing ex vivo cell seeding of the scaffold.

Cu, Co and Cr doping of a calcium phosphate cement influences materials properties and response of human mesenchymal stromal cells.

The application of biologically active metal ions to stimulate cellular reactions is a promising strategy to accelerate bone defect healing. Brushite-forming calcium phosphate cements were modified with low doses of Cu, Co and Cr. The modified cements released the metal ions in vitro in concentrations which were shown to be non-toxic for cells.

Heparin modification of a biomimetic bone matrix modulates osteogenic and angiogenic cell response in vitro.

In this study, the effect of heparin-modified collagen type I/hydroxyapatite (HA) nanocomposites on key processes of bone regeneration - osteogenesis and angiogenesis - was characterised in vitro. Two approaches were applied for heparin modification: it was either integrated during material synthesis (in situ) or added to the porous scaffolds after their fabrication (post). Cultivation of human bone marrow-derived stromal cells (hBMSC), in heparin-modified versus heparin-free scaffolds, revealed a positive effect of the heparin modification on their proliferation and osteogenic differentiation.

A Global Approach for Quantitative Super Resolution and Electron Microscopy on Cryo and Epoxy Sections Using Self-labeling Protein Tags.

Correlative light and electron microscopy (CLEM) is a powerful approach to investigate the molecular ultrastructure of labeled cell compartments. However, quantitative CLEM studies are rare, mainly due to small sample sizes and the sensitivity of fluorescent proteins to strong fixatives and contrasting reagents for EM. Here, we show that fusion of a self-labeling protein to insulin allows for the quantification of age-distinct insulin granule pools in pancreatic beta cells by a combination of super resolution and transmission electron microscopy on Tokuyasu cryosections.

A versatile method for combining different biopolymers in a core/shell fashion by 3D plotting to achieve mechanically robust constructs.

Three-dimensional extrusion of two different biomaterials in a core/shell (c/s) fashion has gained much interest in the last couple of years as it allows for fabricating constructs with novel and interesting properties. We now demonstrate that combining high concentrated (16.7 wt%) alginate hydrogels as shell material with low concentrated, soft biopolymer hydrogels as core leads to mechanically stable and robust 3D scaffolds.

Design and Fabrication of Complex Scaffolds for Bone Defect Healing: Combined 3D Plotting of a Calcium Phosphate Cement and a Growth Factor-Loaded Hydrogel.

Additive manufacturing enables the fabrication of scaffolds with defined architecture. Versatile printing technologies such as extrusion-based 3D plotting allow in addition the incorporation of biological components increasing the capability to restore functional tissues. We have recently described the fabrication of calcium phosphate cement (CPC) scaffolds by 3D plotting of an oil-based CPC paste under mild conditions.

Additive manufacturing of collagen scaffolds by three-dimensional plotting of highly viscous dispersions.

Additive manufacturing (AM) allows the free form fabrication of three-dimensional (3D) structures with distinct external geometry, fitting into a patient-specific defect, and defined internal pore architecture. However, fabrication of predesigned collagen scaffolds using AM-based technologies is challenging due to the low viscosity of collagen solutions, gels or dispersions commonly used for scaffold preparation. In the present study, we have developed a straightforward method which is based on 3D plotting of a highly viscous, high density collagen dispersion.

3D plotting of growth factor loaded calcium phosphate cement scaffolds.

Unlabelled: Additive manufacturing allows to widely control the geometrical features of implants. Recently, we described the fabrication of calcium phosphate cement (CPC) scaffolds by 3D plotting of a storable CPC paste based on water-immiscible carrier liquid. Plotting and hardening is conducted under mild conditions allowing the (precise and local) integration of biological components.

Mechanisms of Beta Cell Dysfunction Associated With Viral Infection.

Type 1 diabetes (T1D) results from genetic predisposition and environmental factors leading to the autoimmune destruction of pancreatic beta cells. Recently, a rapid increase in the incidence of childhood T1D has been observed worldwide; this is too fast to be explained by genetic factors alone, pointing to the spreading of environmental factors linked to the disease. Enteroviruses (EVs) are perhaps the most investigated environmental agents in relationship to the pathogenesis of T1D.

Blood Glucose Homeostasis in the Course of Partial Pancreatectomy--Evidence for Surgically Reversible Diabetes Induced by Cholestasis.

Background And Aim: Partial pancreatic resection is accompanied not only by a reduction in the islet cell mass but also by a variety of other factors that are likely to interfere with glucose metabolism. The aim of this work was to characterize the patient dynamics of blood glucose homeostasis during the course of partial pancreatic resection and to specify the associated clinico-pathological variables.

Methods: In total, 84 individuals undergoing elective partial pancreatic resection were consecutively recruited into this observational trial.

Three-dimensional plotting of a cell-laden alginate/methylcellulose blend: towards biofabrication of tissue engineering constructs with clinically relevant dimensions.

Biofabrication of tissue engineering constructs with tailored architecture and organized cell placement using rapid prototyping technologies is a major research focus in the field of regenerative therapies. This study describes a novel alginate-based material suitable for both cell embedding and fabrication of three-dimensional (3D) structures with predefined geometry by 3D plotting. The favourable printing properties of the material were achieved by using a simple strategy: addition of methylcellulose (MC) to a 3% alginate solution resulted in a strongly enhanced viscosity, which enabled accurate and easy deposition without high technical efforts.

Aged insulin granules display reduced microtubule-dependent mobility and are disposed within actin-positive multigranular bodies.

Insulin secretion is key for glucose homeostasis. Insulin secretory granules (SGs) exist in different functional pools, with young SGs being more mobile and preferentially secreted. However, the principles governing the mobility of age-distinct SGs remain undefined.