Bone defects resulting from trauma, tumor resection and bone diseases represent one of the most pressing health problems in the aging European population. Current treatments of bone defects depend on a functional population of bone-forming (osteogenic cells) to mediate the process of bone regeneration. However during aging, the bone formation capacity decreases as a result of multiple interacting cell-intrinsic and cell-extrinsic mechanisms and the success of treatments in aged patients is in most cases limited. The aim of our project is to develop a new multidisciplinary approach to enhance the regeneration of bone defects in elderly, based on recent advances in cellular reprogramming and tissue engineering. We propose to investigate the extrinsic microenvironment components synthesized by young, embryonic-like osteogenic cells derived from human induced pluripotent stem cells, and test their potential to enhance the function of endogenous bone and vascular cells. We will focus our studies on the patients unable to benefit from the current therapies, due to advanced age and/or systemic conditions limiting their bone formation capacity. We will develop allogeneic, off-the-shelf bone tissue substitutes with the capacity to enhance the function of endogenous cell populations, and evaluate their safety and bone healing potential in preclinical models of bone repair. We hypothesize that ostegenic cells derived from reprogrammed adult/aged somatic cells can synthesize a “rejuvenated”, embryonic-like bone microenvironment with high regenerative capacity and enhance the bone healing processes mediated by aged endogenous cell populations. Our studies will provide new understanding of extrinsic mechanisms governing bone cell biology during aging and open new therapeutic possibilities for the aged patients currently lacking successful outcomes. The developed bone substitutes will also provide a valuable new model for basic biology studies and translational research.

The field of tissue engineering (TE) pursues a noble goal, driven by the urgent need for tissue and organ repair. It is represented by a fairly large and extremely interdisciplinary scientific community. However, so far TE was not able to deliver to the expectations, with only a few examples of successful clinical translation mostly restricted to a particular disease or tissue type. Despite the fact that all major fundamental bottlenecks of conventional TE strategies have long been identified, a universal solution does not seem to be in sight. In this project I propose to launch a radically new approach, a third strategy in tissue engineering (THIRST), which holds the potential to produce a desperately needed technological breakthrough. THIRST relies on a tissue self-assembly from multicellular spheroids encaged within robust 3D printed microscaffolds. THIRST is enabled by a number of cutting-edge methods, some of which became relevant in the context of TE only recently. In combination, these methods offer a variety of new technological possibilities for the area of TE. The objectives of this project are focussed on establishing the means for automated large-scale production of tissue modules, protocols for microscaffold biofunctionalisation, and demonstrating THIRST potential with highly relevant clinical examples - cartilage, representing avascular tissue, and vascularized bone tissue. A distinct feature of THIRST is its universal applicability, meaning that such a tool-box can be further expanded to encompass other types of tissues without substantial adjustments to the basic tissue assembly procedure. The latter is particularly inspiring, taking into account the considerable regulatory hurdles associated with the development of new TE therapies. Due to its unconventional nature, realization of THIRST relies on overcoming several considerable technological challenges addressed by this project.

Fundamental changes occurred in the study of nature between the late 15th and 18th centuries, leading to the emergence of modern science as we know it. This process would have been impossible without Latin as the scientific lingua franca of the era, just as today's science is hard to imagine without English. At present, this crucial role of Latin is insufficiently acknowledged, and the hundreds of thousands of scientific texts written in Latin have largely remained neglected. This severely limits the scope of research into the history of early modern science, an otherwise thriving field. The proposed project intends to decisively advance our understanding of the interrelation of Latin and science in early modern times. By applying the methods of Latin philology, yet at the same time reaching out to historians of science, it will establish early modern scientific literature in Latin as an interdisciplinary research field. This will be accomplished (a) by examining and classifying the formal variety and range of content of this literature to create an overall picture (b) by analysing its function as a medium of communication within and beyond the scientific community. To realise the first of these objectives, a tripartite database for authors, early modern texts, and secondary literature will be compiled and a sourcebook with a selection of digitally searchable texts put together, both of which will be made available online. A monograph will provide an overview structured according to the literary genres of early modern scientific literature in Latin. The second objective will be achieved through a series of interlinked monographs, whose analyses will build on the system of ancient rhetoric, the most important communicative paradigm of the early modern age. On this basis, four key functions of Latin scientific texts will be assessed: naming new phenomena; describing and explaining them; convincing others of the views expressed; and promoting science.