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The literature shows evidence of the mechanical investigation of numerous polymeric dental biomaterials using a static approach. A more representative mechanical analysis of such materials must take into account the dynamic masticatory load of the oral cavity. The aim of this work is to study the dynamic mechanical proprieties and provide an in vitro characterization of 11 3D-printed new dental biomaterials to understand their clinical applications under physiological conditions. The analysis included Dynamical Mechanical Analysis (DMA) and an MTT cytotoxicity assay. The mechanical results at low frequencies (1–11 Hz) show high uncertainty, less fragility, and less strength. The biological results show a significant reduction in cell viability (p < 0.01) at both the 3 and 24 h timepoints, with a degree of recovery observed at 24 h. To assess the clinical potential of dental biomaterials, it is necessary to determine whether there are good dynamic mechanical properties and reduced adverse biological effects on oral cells. This may allow for the facile fabrication via 3D printing of prosthetic devices that can support masticatory loads over long periods of time. Further investigations of the presented polymeric materials are needed, exploring biological assessments for longer than 24 h.

Bisphosphonates (BPs) are successfully used to cure a number of diseases characterized by a metabolic reduction in bone density, such as Osteoporosis, or a neoplastic destruction of bone tissue, such as multiple myeloma and bone metastases. These drugs exert their therapeutic effect by causing a systemic osteoclast depletion that, in turn, is responsible for reduced bone resorption. Unfortunately, in addition to their beneficial activity, BPs can also determine a frightening side effect known as osteonecrosis of the jaw (ONJ). It is generally believed that the inability of osteoclasts to dispose of inflamed/necrotic bone represents the main physiopathological aspect of ONJ. In principle, a therapeutic strategy able to elicit a local re-activation of osteoclast production could counteract ONJ and promote the healing of its lesions. Using an experimental model of Vitamin D3-dependent osteoclastogenesis, we have previously demonstrated that Magnesium is a powerful inducer of osteoclast differentiation. Here we show that, surprisingly, this effect is greatly enhanced by the presence of Zoledronate, chosen for our study because it is the most effective and dangerous of the BPs. This finding allows us to hypothesize that Magnesium might play an important role in the topical therapy of ONJ.

Background: Pemphigus is a life-threatening blistering autoimmune disease. Several forms, characterized by the presence of autoantibodies against different autoantigens, have been described. In Pemphigus Vulgaris (PV), autoantibodies target the cadherin Desmoglein 3 (DSG3), while in Pemphigus foliaceous (PF) autoantibodies target the cadherin Desmoglein 1 (DSG1). Another variant, mucocutaneous Pemphigus, is characterized by the presence of IgG against both DSG1 and DSG3. Moreover, other forms of Pemphigus characterized by the presence of autoantibodies against other autoantigens have been described. With regard to animal models, one can distinguish between passive models, where pathological IgG are transferred into neonatal mice, and active models, where B cells deriving from animals immunized against a specific autoantigen are transferred into immunodeficient mice that develop the disease. Active models recreate PV and a form of Pemphigus characterized by the presence of IgG against the cadherin Desmocollin 3 (DSC3). Further approaches allow to collect sera or B/T cells from mice immunized against a specific antigen to evaluate the mechanisms underlying the onset of the disease. Objective: To develop and characterize a new active model of Pemphigus where mice express auto antibodies against either DSG1 alone, or DSG1 and DSG3, thereby recapitulating PF and mucocutaneous Pemphigus, respectively. In addition to the existing models, with the active models reported in this work, it will be possible to recapitulate and mimic the main forms of pemphigus in adult mice, thus allowing a better understanding of the disease in the long term, including the benefit/risk ratio of new therapies. Results: The new DSG1 and the DSG1/DSG3 mixed models were developed as proposed. Immunized animals, and subsequently, animals that received splenocytes from the immunized donors produce a high concentration of circulating antibodies against the specific antigens. The severity of the disease was assessed by evaluating the PV score, evidencing that the DSG1/DSG3 mixed model exhibits the most severe symptoms among those analyzed. Alopecia, erosions, and blistering were observed in the skin of DSG1, DSG3 and DSG1/DSG3 models, while lesions in the mucosa were observed only in DSG3 and DSG1/DSG3 animals. The effectiveness of the corticosteroid Methyl-Prednisolone was evaluated in the DSG1 and DSG1/DSG3 models, that showed only partial responsiveness.

Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a ~1.4–2-fold increase in the risk of developing AD among T2D patients, the involvement of possible common triggers in the pathogenesis of these two diseases remains largely unknown. Of note, recent mechanistic insights suggest that lipotoxicity could represent the missing ring in the pathogenetic mechanisms linking T2D to AD. Indeed, obesity, which represents the main cause of lipotoxicity, has been recognized as a major risk factor for both pathological conditions. Lipotoxicity can lead to inflammation, insulin resistance, oxidative stress, ceramide and amyloid accumulation, endoplasmic reticulum stress, ferroptosis, and autophagy, which are shared biological events in the pathogenesis of T2D and AD. In the current review, we try to provide a critical and comprehensive view of the common molecular pathways activated by lipotoxicity in T2D and AD, attempting to summarize how these mechanisms can drive future research and open the way to new therapeutic perspectives.

The functioning of many micro-electromechanical devices with parts oscillating at high frequencies require isolation from external vibration. Phononic crystals, presenting band-gaps in the dispersion spectrum, i.e., interval of frequency in which propagating waves are attenuated, can provide an effective solution for vibration shielding at the microscale. In the present work, we design—through numerical simulations—a 3D phononic crystal with a micrometric unit cell able to work as vibration isolator for a micro system. We exploit the direct writing technique based on two-photon polymerization to realize three prototypes of different dimensions. Experimental measurements performed with a Michelson interferometer demonstrate the effectiveness of the proposal.

Logic-in-memory (LIM) circuits based on the material implication logic (IMPLY) and resistive random access memory (RRAM) technologies are a candidate solution for the development of ultra-low power non-von Neumann computing architectures. Such architectures could enable the energy-efficient implementation of hardware accelerators for novel edge computing paradigms such as binarized neural networks (BNNs) which rely on the execution of logic operations. In this work, we present the multi-input IMPLY operation implemented on a recently developed smart IMPLY architecture, SIMPLY, which improves the circuit reliability, reduces energy consumption, and breaks the strict design trade-offs of conventional architectures. We show that the generalization of the typical logic schemes used in LIM circuits to multi-input operations strongly reduces the execution time of complex functions needed for BNNs inference tasks (e.g., the 1-bit Full Addition, XNOR, Popcount). The performance of four different RRAM technologies is compared using circuit simulations leveraging a physics-based RRAM compact model. The proposed solution approaches the performance of its CMOS equivalent while bypassing the von Neumann bottleneck, which gives a huge improvement in bit error rate (by a factor of at least 108) and energy-delay product (projected up to a factor of 1010).

Different in-memory computing paradigms enabled by emerging non-volatile memory technologies are promising solutions for the development of ultra-low-power hardware for edge computing. Among these, SIMPLY, a smart logic-in-memory architecture, provides high reconfigurability and enables the in-memory computation of both logic operations and binarized neural networks (BNNs) inference. However, operation-specific hardware accelerators can result in better performance for a particular task, such as the analog computation of the multiply and accumulate operation for BNN inference, but lack reconfigurability. Nonetheless, a solution providing the flexibility of SIMPLY while also achieving the high performance of BNN-specific analog hardware accelerators is missing. In this work, we propose a novel in-memory architecture based on 1T1R crossbar arrays, which enables the coexistence on the same crossbar array of both SIMPLY computing paradigm and the analog acceleration of the multiply and accumulate operation for BNN inference. We also highlight the main design tradeoffs and opportunities enabled by different emerging non-volatile memory technologies. Finally, by using a physics-based Resistive Random Access Memory (RRAM) compact model calibrated on data from the literature, we show that the proposed architecture improves the energy delay product by >103 times when performing a BNN inference task with respect to a SIMPLY implementation.

Stem cell fate and behavior are affected by the bidirectional communication of cells and their local microenvironment (the stem cell niche), which includes biochemical cues, as well as physical and mechanical factors. Stem cells are normally cultured in conventional two-dimensional monolayer, with a mechanical environment very different from the physiological one. Here, we compare culture of rat mesenchymal stem cells on flat culture supports and in the “Nichoid”, an innovative three-dimensional substrate micro-engineered to recapitulate the architecture of the physiological niche in vitro. Two versions of the culture substrates Nichoid (single-layered or “2D Nichoid” and multi-layered or “3D Nichoid”) were fabricated via two-photon laser polymerization in a biocompatible hybrid organic-inorganic photoresist (SZ2080). Mesenchymal stem cells, isolated from rat bone marrow, were seeded on flat substrates and on 2D and 3D Nichoid substrates and maintained in culture up to 2 weeks. During cell culture, we evaluated cell morphology, proliferation, cell motility and the expression of a panel of 89 mesenchymal stem cells’ specific genes, as well as intracellular structures organization. Our results show that mesenchymal stem cells adhered and grew in the 3D Nichoid with a comparable proliferation rate as compared to flat substrates. After seeding on flat substrates, cells displayed large and spread nucleus and cytoplasm, while cells cultured in the 3D Nichoid were spatially organized in three dimensions, with smaller and spherical nuclei. Gene expression analysis revealed the upregulation of genes related to stemness and to mesenchymal stem cells’ features in Nichoid-cultured cells, as compared to flat substrates. The observed changes in cytoskeletal organization of cells cultured on 3D Nichoids were also responsible for a different localization of the mechanotransducer transcription factor YAP, with an increase of the cytoplasmic retention in cells cultured in the 3D Nichoid. This difference could be explained by alterations in the import of transcription factors inside the nucleus due to the observed decrease of mean nuclear pore diameter, by transmission electron microscopy. Our data show that 3D distribution of cell volume has a profound effect on mesenchymal stem cells structure and on their mechanobiological response, and highlight the potential use of the 3D Nichoid substrate to strengthen the potential effects of MSC in vitro and in vivo.

Since the pioneering work of Ashkin and coworkers, back in 1970, optical manipulation gained an increasing interest among the scientific community. Indeed, the advantages and the possibilities of this technique are unsubtle, allowing for the manipulation of small particles with a broad spectrum of dimensions (nanometers to micrometers size), with no physical contact and without affecting the sample viability. Thus, optical manipulation rapidly found a large set of applications in different fields, such as cell biology, biophysics, and genetics. Moreover, large benefits followed the combination of optical manipulation and microfluidic channels, adding to optical manipulation the advantages of microfluidics, such as a continuous sample replacement and therefore high throughput and automatic sample processing. In this work, we will discuss the state of the art of these optofluidic devices, where optical manipulation is used in combination with microfluidic devices. We will distinguish on the optical method implemented and three main categories will be presented and explored: (i) a single highly focused beam used to manipulate the sample, (ii) one or more diverging beams imping on the sample, or (iii) evanescent wave based manipulation.

We propose a novel method to fabricate three-dimensional magnetic microparts, which can be integrated in functional microfluidic networks and lab-on-a-chip devices, by the combination of two-photon microfabrication and selective electroless plating. In our experiments, magnetic microparts could be successfully fabricated by optimizing various experimental conditions of electroless plating. In addition, energy dispersive X-ray spectrometry (EDS) clarified that iron oxide nanoparticles were deposited onto the polymeric microstructure site-selectively. We also fabricated magnetic microrotors which could smoothly rotate using common laboratory equipment. Since such magnetic microparts can be remotely driven with an external magnetic field, our fabrication process can be applied to functional lab-on-a-chip devices for analytical and biological applications.