Publications

Gradients of signaling pathways within the intestinal stem cell (ISC) niche are instrumental for cellular compartmentalization and tissue function, yet how are they sensed by the epithelium is still not fully understood. Here a new in vitro model of the small intestine based on primary epithelial cells (i), apically accessible (ii), with native tissue mechanical properties and controlled mesh size (iii), 3D villus-like architecture (iv), and precisely controlled biomolecular gradients of the ISC niche (v) is presented. Biochemical gradients are formed through hydrogel-based scaffolds by free diffusion from a source to a sink chamber. To confirm the establishment of spatiotemporally controlled gradients, light-sheet fluorescence microscopy and in-silico modeling are employed. The ISC niche biochemical gradients coming from the stroma and applied along the villus axis lead to the in vivo-like compartmentalization of the proliferative and differentiated cells, while changing the composition and concentration of the biochemical factors affects the cellular organization along the villus axis. This novel 3D in vitro intestinal model derived from organoids recapitulates both the villus-like architecture and the gradients of ISC biochemical factors, thus opening the possibility to study in vitro the nature of such gradients and the resulting cellular response.© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.

JTD Keywords: 3d architectures, biomolecular gradients, colon, crypt, engineering organoids, hydrogels, identification, in silico modeling, intestinal stem cell niches, light sheet fluorescence microscopy, niche, permeability, photolithography, regeneration, villus, wnt, 3d architectures, Biomolecular gradients, Engineering organoids, In silico modeling, Intestinal stem cell niches, Light sheet fluorescence microscopy, Photolithography, Stem-cell

Concave surfaces have shown to promote bone regeneration in vivo. However, bone scaffolds obtained by direct ink writing, one of the most promising approaches for the fabrication of personalized bone grafts, consist mostly of convex surfaces, since they are obtained by microextrusion of cylindrical strands. By modifying the geometry of the nozzle, it is possible to print 3D structures composed of non-cylindrical strands and favor the presence of concave surfaces. In this work, we compare the in vivo performance of 3D-printed calcium phosphate scaffolds with either conventional cylindrical strands or star-shaped strands, in a rabbit femoral condyle model. Mono cortical defects, drilled in contralateral positions, are randomly grafted with the two scaffold configurations, with identical composition. The samples are explanted eight weeks post-surgery and assessed by ??-CT and resin embedded histological observations. The results reveal that the scaffolds containing star-shaped strands have better osteoconductive properties, guiding the newly formed bone faster towards the core of the scaffolds, and enhance bone regeneration, although the increase is not statistically significant (p > 0.05). This new approach represents a turning point towards the optimization of pore shape in 3D-printed bone grafts, further boosting the possibilities that direct ink writing technology offers for patient-specific applications.

JTD Keywords: 3d printing, biomimetic calcium phosphate, bone regeneration, in vivo, pore architecture, 3d printing, Architecture, Biomimetic calcium phosphate, Bone regeneration, Calcium-phosphate scaffolds, Geometry, Growth, Implants, In vivo, Induction, Microporosity, Osteoinduction, Pore architecture, Scaffold, Surfaces, Tissue

Animals in their ecological context behave not only in response to external events, such as opportunities and threats but also according to their internal needs. As a result, the survival of the organism is achieved through regulatory behaviour. Although homeostatic and allostatic principles play an important role in such behaviour, how an animal's brain implements these principles is not fully understood yet. In this paper, we propose a new model of regulatory behaviour inspired by the functioning of the medial Reticular Formation (mRF). This structure is spread throughout the brainstem and has shown generalized Central Nervous System (CNS) arousal control and fundamental action-selection properties. We propose that a model based on the mRF allows the flexibility needed to be implemented in diverse domains, while it would allow integration of other components such as place cells to enrich the agent's performance. Such a model will be implemented in a mobile robot that will navigate replicating the behaviour of the sand-diving lizard, a benchmark for regulatory behaviour. © 2020 Elsevier B.V.. All rights reserved.

JTD Keywords: Action selection, Allostasi, Allostasis, Animal brain, Animals, Behavior-based, Brainstem, Central nervous systems, Cognitive architecture, Cognitive architectures, Elsevier, Homeostasis, Homoeostasis, Magnetorheological fluids, Regulatory behavior, Regulatory behaviour, Reticular formation, Robots

We present a new computational framework for modeling moral decision-making in artificial agents based on the notion of ‘Machine Morality as Cooperation’. This framework integrates recent advances from cross-disciplinary moral decision-making literature into a single architecture. We build upon previous work outlining cognitive elements that an artificial agent would need for exhibiting latent morality, and we extend it by providing a computational realization of the cognitive architecture of such an agent. Our work has implications for cognitive and social robotics. Recent studies in human neuroimaging have pointed to three different decision-making processes, Pavlovian, model-free and model-based, that are defined by distinct neural substrates in the brain. Here, we describe how computational models of these three cognitive processes can be implemented in a single cognitive architecture by using the distributed and hierarchical organization proposed by the DAC theoretical framework. Moreover, we propose that a pro-social drive to cooperate exists at the Pavlovian level that can also bias the rest of the decision system, thus extending current state-of-the-art descriptive models based on harm-aversion.

JTD Keywords: Morality, Moral decision-making, Computational models, Cognitive architectures, Cognitive robotics, Human-robot interaction

In this paper, we argue that the future of Artificial Intelligence research resides in two keywords: integration and embodiment. We support this claim by analyzing the recent advances in the field. Regarding integration, we note that the most impactful recent contributions have been made possible through the integration of recent Machine Learning methods (based in particular on Deep Learning and Recurrent Neural Networks) with more traditional ones (e.g. Monte-Carlo tree search, goal babbling exploration or addressable memory systems). Regarding embodiment, we note that the traditional benchmark tasks (e.g. visual classification or board games) are becoming obsolete as state-of-the-art learning algorithms approach or even surpass human performance in most of them, having recently encouraged the development of first-person 3D game platforms embedding realistic physics. Building on this analysis, we first propose an embodied cognitive architecture integrating heterogeneous subfields of Artificial Intelligence into a unified framework. We demonstrate the utility of our approach by showing how major contributions of the field can be expressed within the proposed framework. We then claim that benchmarking environments need to reproduce ecologically-valid conditions for bootstrapping the acquisition of increasingly complex cognitive skills through the concept of a cognitive arms race between embodied agents.

JTD Keywords: Cognitive Architectures, Embodied Artificial Intelligence, Evolutionary Arms Race, Unified Theories of Cognition

A major challenge in cognitive science and AI is to understand how intelligent agents might be able to predict mental states of other agents during complex social interactions. What are the computational principles of such a Theory of Mind (ToM)? In previous work, we have investigated hypotheses of how the human brain might realize a ToM of other agents in a multi-agent social scenario. In particular, we have proposed control-based cognitive architectures to predict the model of other agents in a game-theoretic task (Battle of the Exes). Our multi-layer architecture implements top-down predictions from adaptive to reactive layers of control and bottom-up error feedback from reactive to adaptive layers. We tested cooperative and competitive strategies among different multi-agent models, demonstrating that while pure RL leads to reasonable efficiency and fairness in social interactions, there are other architectures that can perform better in specific circumstances. However, we found that even the best predictive models fall short of human data in terms of stability of social convention formation. In order to explain this gap between humans and predictive AI agents, in this work we propose introducing the notion of trust in the form of mutual agreements between agents that might enhance stability in the formation of conventions such as turn-taking.

JTD Keywords: Cognitive Architectures, Game Theory, Multi-Agent Models, Reinforcement Learning, Theory of Mind

In this study, polylactic acid (PLA) and polyethylene glycol (PEG) were combined with soluble CaP glass particles and processed by rapid prototyping to obtain fully biodegradable structures for Tissue Engineering applications. The obtained 3D biodegradable structures were characterized in terms of their architecture and mechanical properties. The scaffold morphology, internal micro-architecture and mechanical properties were evaluated using Scanning Electron Microscopy (SEM), micro-computed tomography (micro-CT) and mechanical testing, respectively. Well defined structures with pore size of 350-400μm (in the axial view), struts width of approximately 70-80μm, and a porosity ranging between 60-65% were obtained. The combination RP and PLA/PEG/CaP glass turned into promising fully degradable, mechanically stable, bioactive and biocompatible composite scaffolds for TE.

JTD Keywords: Axial view, Biodegradable composites, Composite scaffolds, Glass particles, Mechanically stable, Micro architectures, Micro computed tomography (micro-CT), Poly lactic acid, Scaffold morphology, Tissue engineering applications, Well-defined structures, Bioactive glass, Mechanical properties, Mechanical testing, Polyethylene glycols, Polymer blends, Rapid prototyping, Scaffolds (biology), Scanning electron microscopy, Computerized tomography

This paper presents a novel teleoperation paradigm, the Virtual Robot (VR), focused on facilitating the surgeon tasks in minimally invasive robotic surgery. The VR has been conceived to increase the range of applicability of traditional master slave teleoperation architectures by means of an automatic cooperative behavior that assigns the execution of the ongoing task to the most suitable robot. From the user's point of view, the VR internal operation must be automatic and transparent. A set of evaluation indexes have been developed to obtain the suitability of each robot as well as an algorithm to determine the optimal instant of time to execute a task transfer. Several experiments demonstrate the usefulness of the VR, as well as indicates the next steps of the research.

JTD Keywords: Cameras, Collision avoidance, Indexes, Joints, Robots, Surgery, Trajectory, Medical robotics, Surgery, Telerobotics, VR internal operation, Automatic cooperative behavior, Evaluation indexes, Master slave teleoperation architectures, Minimally invasive robotic surgery, Task transfer, Virtual robot