Shaping Synthetic Multicellular and Complex Multimaterial Tissues via Embedded Extrusion-Volumetric Printing of Microgels.

In living tissues, cells express their functions following complex signals from their surrounding microenvironment. Capturing both hierarchical architectures at the micro- and macroscale, and anisotropic cell patterning remains a major challenge in bioprinting, and a bottleneck toward creating physiologically-relevant models. Addressing this limitation, a novel technique is introduced, termed Embedded Extrusion-Volumetric Printing (EmVP), converging extrusion-bioprinting and layer-less, ultra-fast volumetric bioprinting, allowing spatially pattern multiple inks/cell types. Light-responsive microgels are developed for the first time as bioresins (µResins) for light-based volumetric bioprinting, providing a microporous environment permissive for cell homing and self-organization. Tuning the mechanical and optical properties of gelatin-based microparticles enables their use as support bath for suspended extrusion printing, in which features containing high cell densities can be easily introduced. µResins can be sculpted within seconds with tomographic light projections into centimeter-scale, granular hydrogel-based, convoluted constructs. Interstitial microvoids enhanced differentiation of multiple stem/progenitor cells (vascular, mesenchymal, neural), otherwise not possible with conventional bulk hydrogels. As proof-of-concept, EmVP is applied to create complex synthetic biology-inspired intercellular communication models, where adipocyte differentiation is regulated by optogenetic-engineered pancreatic cells. Overall, EmVP offers new avenues for producing regenerative grafts with biological functionality, and for developing engineered living systems and (metabolic) disease models.

Mesenchymal Stromal Cells in Neuroblastoma: Exploring Crosstalk and Therapeutic Implications.

Neuroblastoma (NB) is the second most common solid cancer in childhood, accounting for 15% of cancer-related deaths in children. In high-risk NB patients, the majority suffers from metastasis. Despite intensive multimodal treatment, long-term survival remains <40%. The bone marrow (BM) is among the most common sites of distant metastasis in patients with high-risk NB. In this environment, small populations of tumor cells can persist after treatment (minimal residual disease) and induce relapse. Therapy resistance of these residual tumor cells in BM remains a major obstacle for the cure of NB. A detailed understanding of the microenvironment and its role in tumor progression is of utmost importance for improving the treatment efficiency of NB. In BM, mesenchymal stromal cells (MSCs) constitute an important part of the microenvironment, where they support hematopoiesis and modulate immune responses. Their role in tumor progression is not completely understood, especially for NB. Although MSCs have been found to promote epithelial-mesenchymal transition, tumor growth, and metastasis and to induce chemoresistance, some reports point toward a tumor-suppressive effect of MSCs. In this review, we aim to compile current knowledge about the role of MSCs in NB development and progression. We evaluate arguments that depict tumor-supportive versus -suppressive properties of MSCs in the context of NB and give an overview of factors involved in MSC-NB crosstalk. A focus lies on the BM as a metastatic niche, since that is the predominant site for NB metastasis and relapse. Finally, we will present opportunities and challenges for therapeutic targeting of MSCs in the BM microenvironment.

Viral hepatitis in a multi-ethnic neighborhood in the Netherlands: results of a community-based study in a low prevalence country.

OBJECTIVES: The prevalence of viral hepatitis varies worldwide. Although the prevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection is generally low in Western countries, pockets of higher prevalence may exist in areas with large immigrant populations. The aim of this study was to obtain further information on the prevalence of viral hepatitis in a multi-ethnic area in the Netherlands. METHODS: We conducted a community-based study in a multi-ethnic neighborhood in the city of Rotterdam, the Netherlands, including both native Dutch and migrant participants, who were tested for serological markers of hepatitis A, hepatitis B, and hepatitis C infection. RESULTS: Markers for hepatitis A infection were present in 68% of participants. The prevalence of hepatitis B core antibodies (anti-HBc), a marker for previous or current infection, was 20% (58/284). Prevalence of hepatitis A and B varied by age group and ethnicity. Two respondents (0.7%) had chronic HBV infection. The prevalence of hepatitis C was 1.1% (3/271). High levels of isolated anti-HBc were found. CONCLUSIONS: We found a high prevalence of (previous) viral hepatitis infections. This confirms previous observations in ethnic subgroups from a national general population study and illustrates the high burden of viral hepatitis in areas with large immigrant populations.

Control measures used during lymphogranuloma venereum outbreak, Europe.

To assess the response to the reemergence of lymphogranuloma venereum, we conducted a cross-sectional survey by administering a structured questionnaire to representatives from 26 European countries. Responses were received from 18 countries. The ability to respond quickly and the measures used for outbreak detection and control varied. Evidence-based criteria were not consistently used to develop recommendations. We did not develop criteria to determine the effectiveness of the recommendations. The degree of preparedness for an unexpected outbreak, as well as the ability of countries to respond quickly to alerts, varied, which indicates weaknesses in the ability to control an outbreak. More guidance is needed to implement and evaluate control measures used during international outbreaks.

Needlestick injury and accidental exposure to blood: the need for improving the hepatitis B vaccination grade among health care workers outside the hospital.

To describe the characteristics of needlestick injuries occurring to health care workers outside the hospital, a new case report form was implemented and analyzed after 12 months. A total of 144 incidents were reported. Of the needlestick injuries in nursing assistants, 84% involved an insulin needle or pen. Thirty-five percent of all health care workers and 47% of the nursing assistants were not vaccinated against hepatitis B. Hepatitis B vaccination grade in health care workers outside the hospital should be improved, in particular among nursing assistants.