Cluster-assembled zirconia substrates promote long-term differentiation and functioning of human islets of Langerhans

Ex vivo expansion and differentiation of human pancreatic ß-cell are enabling steps of paramount importance for accelerating the development of therapies for diabetes. The success of regenerative strategies depends on their ability to reproduce the chemical and biophysical properties of the microenvironment in which ß-cells develop, proliferate and function. In this paper we focus on the biophysical properties of the extracellular environment and exploit the cluster-assembled zirconia substrates with tailored roughness to mimic the nanotopography of the extracellular matrix. We demonstrate that ß-cells can perceive nanoscale features of the substrate and can convert these stimuli into mechanotransductive processes which promote long-term in vitro human islet culture, thus preserving ß-cell differentiation and function. Proteomic and quantitative immunofluorescence analyses demonstrate that the process is driven by nanoscale topography, via remodelling of the actin cytoskeleton and nuclear architecture. These modifications activate a transcriptional program which stimulates an adaptive metabolic glucose response. Engineered cluster-assembled substrates coupled with proteomic approaches may provide a useful strategy for identifying novel molecular targets for treating diabetes mellitus and for enhancing tissue engineering in order to improve the efficacy of islet cell transplantation therapies

Vascularization in Oral and Maxillofacial Tissue Engineering

This book provides a thorough, up-to-date description of the scientific basis and concepts of tissue engineering in the oral and maxillofacial region. The opening chapters present an introduction to tissue engineering, describe the roles of biomaterials and stem cells, discuss the use of growth factors, and examine potential adverse reactions. The challenges of soft and hard tissue engineering for oral and maxillofacial reconstruction are then considered in detail. It is explained what has been achieved to date, and potential future perspectives are explored. The importance and the verification of adequate vascularization are discussed, and a further focus is the use of 3D printing, both in the planning and production of scaffolds and in the bioprinting of cells and biomaterials. Information is also included on safety, efficacy, and regulatory aspects. Tissue Engineering in Oral and Maxillofacial Surgery will be of interest to all researchers and practitioners who wish to learn more about the potential of tissue engineering to revolutionize practice in oral and maxillofacial surgery

Cellular and Molecular Responses to Gravitational Force-Triggered Stress in Cells of the Immune System

Sensitivity of the human immune system to microgravity has been supposed since the first Apollo missions and was demonstrated during several space missions in the past. In vitro experiments demonstrated that cells of the immune system are exceptionally sensitive to microgravity. Therefore, serious concerns arose whether spaceflight-associated immune system weakening ultimately precludes the expansion of human presence beyond Earth’s orbit. In human cells, gravitational forces may be sensed by an individual cell in the context of altered extracellular matrix mechanics, cell shape, cytoskeletal organization, or internal prestress in the cell–tissue matrix. The development of cellular mechanosensitivity and signal transduction was probably an evolutionary requirement to enable our cells to sense their individual microenvironment. Therefore it is possible that the same mechanisms, which enable human cells to sense and to cope with mechanical stress, are potentially dangerous in microgravity. This chapter reviews the most recent developments in investigation to elucidate the influence of microgravity on immune cell signaling and functions and hereby bridges the phenotypic changes to transcriptome and epigenetic regulators