University of Genoa

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    Sustainable Biomaterial for Tissue Engineering Applications

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    The development of biomaterials for tissue engineering holds immense potential in addressing critical medical challenges, while meeting the need for alternative eco-friendly solutions. This doctoral thesis explores innovative biomaterial-based approaches for two distinct tissue engineering applications: to provide faithful in vitro models of the central nervous system (CNS), and to propose an innovative solution for pediatric cranioplasty. The use of sustainable and biocompatible materials is central to these studies. By combining material science, biomedical engineering and biology I propose new approaches to overcome the limitations of most conventional solutions. Firstly, I investigated the potential of chitosan, a crustacean waste-derived biomaterial, in supporting the adhesion and neuronal differentiation of human induced pluripotent stem cells (hiPSCs) in simplified 2D in vitro models. Chitosan is renowned for its low cost, biocompatibility, biodegradability, antibacterial activity as well as its bioaffinity. In this thesis, I propose the use of chitosan as an alternative adhesion factor to Matrigel, the gold standard for inducing the neuronal differentiation of hiPSCs. Though extensively used, Matrigel derives from the extracellular matrix (ECM) of mouse sarcoma and has risen several concerns about its xenogenicity and batch-to-batch variability. Additionally, Matrigel is not able to support the survival of fully differentiated hiPSCs-derived neurons (iNeurons). In my work, I demonstrated that chitosan is not only able to support the early-stage neuronal differentiation of hiPSCS, but also the survival and maturation of iNeurons and the formation of a functional neuronal network, thus providing an alternative, green-based solution for in vitro modelling of the CNS. To further improve my work and address the need for more complex and representative in vitro CNS models, I leveraged the versatility of chitosan to propose 3D thermosensitive hydrogels that mimic the biochemical composition and characteristics of the brain ECM. The tuneable properties and ease of modification of chitosan thermogels, allow the formulation of more faithful in vitro models that support the neuronal differentiation of hiPSCs, paving the way for the development of personalised testing platforms for neuropathological studies and for the development of new drugs. Finally, I developed and leveraged a novel scaffold, derived from porcine MENiscus Decellularization (MEND), as an alternative material for pediatric cranioplasty. Traditional cranioplasty techniques offer exceptional outcomes in adult patients, however their failure rate increases dramatically in children, mainly due to higher infection and bone resorption incidence. To address the limitations in biodegradability, biocompatibility, and osteoconductivity of traditional methods, I leveraged decellularized porcine cartilage to support the osteogenic differentiation of human periosteal progenitor cells, mesenchymal-line cells that are found within the periosteum. The innovative decellularization process allow the formation of hollow channels that run cross-sectionally along MEND and which are pivotal for scaffold seeding and for the infiltration of new vasculature and cells once MEND is implanted in vivo. I studied the osteogenic potential of human periosteal progenitors and compared it to the osteogenic potential of human osteoblasts (positive control). Then I investigated ability of MEND in supporting the osteogenic differentiation of human periosteal progenitors. I demonstrated that periosteal cells differentiated within MEND show a robust osteogenic phenotype, similarly to human osteoblasts, thus being interesting candidates for cranial bone repair.Together, these studies demonstrate the versatility and potential of sustainable biomaterials in advancing tissue engineering and regenerative medicine. By addressing specific challenges in neural differentiation, 3D brain tissue modelling, and in pediatric cranioplasty, this work contributes to the development of innovative, biocompatible solutions with translational potential in clinical settings

    Pseudorapidity distributions of charged hadrons in lead-lead collisions at sqrt(s)=5.36TeV

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    The pseudorapidity (η) distributions of charged hadrons are measured using data collected at the highest ever nucleon-nucleon center-of-mass energy of sjavax.xml.bind.JAXBElement@76d3de32=5.36TeV for collisions of lead-lead ions. The data were recorded by the CMS experiment at the LHC in 2022 and correspond to an integrated luminosity of 0.30±0.03μb−1. Using the CMS silicon pixel detector, the yields of primary charged hadrons produced in the range |η|<2.6 are reported. The evolution of the midrapidity particle density as a function of collision centrality is also reported. In the 5% most central collisions, the charged-hadron η density in the range |η|<0.5 is found to be 2032±91(syst), with negligible statistical uncertainty. This result is consistent with an extrapolation from nucleus-nucleus collision data at lower center-of-mass energies. Comparisons are made to various Monte Carlo event generators and to previous measurements of lead-lead and xenon-xenon collisions at similar collision energies. These new data detail the dependence of particle production on the collision energy, initial collision geometry, and the size of the colliding nuclei

    The “Arrow Factor” in Gluteoplasty and Brazilian Butt Lift

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    The gluteal region has become a rising area of interest in plastic surgery in recent years, as reflected in body contouring surgery trends. In this study, the authors explain what the arrow effect consists of and how to highlight it during a Brazilian butt lift or a gluteal liposculpture: liposuction of the sacral triangle, fat grafting of the upper gluteal quadrants, liposuction of the dimples of Venus and of the midline superficially to the spinal column, and fat grafting of the erector spinae muscles

    The Influence of Implant Surface Modification on Marginal Bone Loss and Periodontal Health: A Cross-Over Randomized Clinical Trial

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    Background: Edentulism rehabilitation with short implants is a procedure of proven efficacy. To improve the biological aspects of the interface between the implant and hard and soft tissues, different implant and prosthetic surface treatments have been proposed, producing contrasting results. The aim of present study is to compare implants and transmucosal components with an anodized collar with those with a traditionally machined collar in terms of Marginal bone loss and periodontal indexes. Materials and Methods: 30 patients were treated with two adjacent 6 mm length and 4.3 mm diameter implants (Shard short, Mech&Human, Grisignano di Zocco, Italy), one with an anodized collar (Test group) and one with a traditional machined collar (Control group), randomly positioned. Definitive transmucosal straight multiunit abutments (MUAs) (Mech&Human, Grisignano di Zocco, Italy) of height 1 mm, with differentially treated surfaces, were immediately screwed. After 3 months, prosthetic rehabilitation with splinted zirconia crowns screwed to the MUAs was made. Marginal bone levels (MBLs) were evaluated at the time of implant placement (T0), after 3 months (T3), after 6 and 12 months (T6 and T12) through periapical radiographies. Periodontal indexes (probing depth [PD], bleeding on probing [BoP], and plaque index [PlI]) were evaluated at the same timepoints, with the maximum follow-up of 12 months. Results: Average marginal bone loss at T3 was 0.40 ± 0.31 mm in the Test group and 0.42 ± 0.40 mm in the Control group (p = 0.76), reaching 0.63 ± 0.41 and 0.78 ± 0.43 mm at T12 in the Test and the Control groups, respectively (p = 0.94). Physiological PDs, with average values ranging between 1.48 and 2.1 mm, were revealed around the implants in both the groups, and The PlI ranged between 0 and 1 in most cases, and BoP appeared in some cases with isolated bleeding spots after probe passing (mean values ranging between 0.20 ± 0.41 and 0.50 ± 0.52), with no significant differences between groups. Conclusions: Surface treatment with anodization of implant collar and transmucosal components seem to not influence marginal bone stability at 1-year follow-up, nor the condition of periodontal tissues. Long-term follow-ups are needed to confirm the results. Trial Registration: ClinicalTrials.gov identifier: NCT05766878

    Electrospun Agar-Based Nanocomposite Mats for Artworks Disinfection

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    Disinfection is a critical and irreversible process in the restoration of Cultural Heritage, significantly impacting the long-term preservation of artworks. This study presents an innovative approach for obtaining ready-to-use electrospun mats composed of Agar nanofibers incorporating silver and gold nanoparticles. Electrospinning, a cost-effective and simple technique that utilizes a high electric field [1], enables the fabrication of highly porous mats with a high surface-to-volume ratio. These features facilitate controlled solvent release, easy removal from treated surfaces, and enhanced cleaning and disinfection capabilities through the incorporation of functional nanomaterials [2]. Aqueous solutions containing Agar, a polysaccharide derived from algae [3], and the co-spinning agent poly(ethylene oxide) (PEO, 300K g/mol) were prepared at a total concentration of 3% w/v (50:50 Agar/PEO ratio) and used as a polymeric matrix for the in-situ synthesis of the metal nanoparticles through a green bottom-up approach that eliminates the need for reducing agents. The nanoparticles-containing suspensions were characterized by rheological, spectroscopic, and TEM analyses to assess viscosity, polymer-filler interactions, and nanoparticles morphology and stability on time before being processed by electrospinning. Once prepared, the electrospun mats were characterized via Atomic Force Microscopy (AFM) and Field-Emission Scanning Electron Microscopy (FE-SEM) to evaluate surface roughness and nanocomposite morphology, mechanical testing, contact angle measurements to assess wettability and hydrophilicity, and SEM-EDX analysis to study the nanoparticles distribution within the polymeric matrix. Leveraging the unique antibacterial and antifungal properties of noble metal nanoparticles [4], these nanocomposite mats were successfully tested against selected bacterial and fungal species. The results obtained pave the way for the development of nanostructured mats that could revolutionize current disinfection and cleaning methodologies through their peculiar physico-chemical properties. Future studies will explore the thermoplasmonic properties of mat with gold nanoparticles for biofilm eradication, offering a novel strategy for artwork conservation

    Stroke Detection and Monitoring by Means of a Multifrequency Microwave Inversion Approach

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    In the area of biomedical diagnostics, microwave imaging techniques have been recently proposed for performing brain stroke detection and monitoring. Indeed, theoretically, these techniques make it possible to meet the timeliness requirements of such a diagnosis with portable systems. Moreover, relying on the use of microwaves, they are noninvasive and allow continuous monitoring of critical patients. In this paper, the microwave imaging problem is solved by exploiting multifrequency data by an inexact-Newton method formulated in the framework of non-constant exponent Lebesgue spaces. First, the method is numerically validated with three-dimensional head models affected by anatomically-realistic strokes. Then, a further assessment through experimental data obtained with a cylindrical phantom is conducted. A quite accurate reconstruction of the variations of dielectric properties inside the patient’s head due to the insurgence of stroke is obtained in both numerical and experimental cases, showing the potentiality of the proposed approach

    Clinical and metabolic profiles in behavioural frontotemporal dementia: Impact of age at onset

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    Aim: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder, with considerable variability of age-at-onset. We explored clinical and metabolic differences between early- and late-onset behavioural FTD (bvFTD), assuming that they might represent different disease phenotypes. Materials and methods: We retrospectively studied consecutive patients diagnosed with prodromal or overt bvFTD with [18F]FDG PET scan, neuropsychological assessment (NPS), and Neuropsychiatric Inventory (NPI) available at baseline. Patients were divided into three groups based on age-at-onset: early onset-bvFTD (EO-bvFTD, age<70), late onset-bvFTD (LO-bvFTD, age 70–75) and very late onset-bvFTD (vLO-bvFTD, age>75). NPS and NPI were compared between groups and in the subset of prodromal patients, to study different syndromic phenotypes. Voxel-based analysis compared brain [18F]FDG PET of EO-bvFTD, LO-bvFTD and vLO-bvFTD independently, with respect to healthy controls, to explore metabolic differences. An inter-regional metabolic covariance analysis was performed in frontal lobe subregions, to explore differences in brain connectivity. Moreover, we supported our result using a correlation-based approach on clinical and metabolic variables. Results: 101 bvFTD (62 prodromal bvFTD) were enrolled (EO-bvFTD: n = 36, prodromal n = 21; LO-bvFTD: n = 36, prodromal: n = 22; vLO-bvFTD: n = 29, prodromal: n = 19). Greater verbal memory deficit was evident in LO-bvFTD and vLO-bvFTD compared to EO-bvFTD (immediate recall: p = .018; p = .024; delayed recall: both p = .001, respectively), with similar results in the subset of prodromal patients. EO-bvFTD and LO-bvFTD had a higher behavioural severity than vLO-bvFTD. LO-bvFTD and vLO-bvFTD showed more widespread relative hypometabolism, with a greater involvement of posterior, subcortical and temporo-limbic regions compared with EO-bvFTD. Moreover, vLO-bvFTD showed a different pattern of intrafrontal metabolic covariance compared to EO-bvFTD and LO-bvFTD. Discussion: The cognitive–behavioural profile of bvFTD differs between early- and late-onset, already from the prodromal stage of the disease. Both metabolic pattern and functional connectivity vary based on age-at-onset. Understanding these differences could contribute to improve diagnostic accuracy and understanding the underling pathological heterogeneity

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