Development of novel multi-substituted apatite nanophases with advanced functionalities for bone regeneration

In the field of bone substitutes is highly researched an innovative material able to fill gaps with high mechanical performances and able to stimulate cell response, permitting the complete restoration of the bone portion. In this respect, the synthesis of new bioactive materials able to mimic the compositional, morphological and mechanical features of bone is considered as the elective approach for effective tissue regeneration. Hydroxyapatite (HA) is the main component of the inorganic part of bone. Additionally ionic substitution can be performed in the apatite lattice producing different effects, depending from the selected ions. Magnesium, in substitution of calcium, and carbonate, in substitution of phosphate, extensively present in the biological bones, are able to improve properties naturally present in the apatitic phase, (i.e. biomimicry, solubility e osteoinductive properties). Other ions can be used to give new useful properties, like antiresorptive or antimicrobial properties, to the apatitic phase. This thesis focused on the development of hydroxyapatite nanophases with multiple ionic substitutions including gallium, or zinc ions, in association with magnesium and carbonate, with the purpose to provide double synergistic functionality as osteogenic and antibacterial biomaterial. Were developed bioactive materials based on Sr-substituted hydroxyapatite in the form of sintered targets. The obtained targets were treated with Pulsed Plasma Deposition (PED) resulting in the deposition of thin film coatings able to improve the roughness and wettability of PEEK, enhancing its osteointegrability. Were investigated heterogeneous gas-solid reactions, addressed to the biomorphic transformations of natural 3D porous structures into bone scaffolds with biomimetic composition and hierarchical organization, for application in load-bearing sites. The kinetics of the different reactions of the process were optimized to achieve complete and controlled phase transformation, maintaining the original 3-D morphology. Massive porous scaffolds made of ion-substituted hydroxyapatite and bone-mimicking structure were developed and tested in 3-D cell culture models

Artificial molecular-level machines with [Ru(bpy)3]2

A molecular-level machine is an assembly of a discrete number of molecular components (that is, a supramolecular structure) designed to perform mechanical-like movements (output) as a consequence of appropriate external stimuli (input). Like macroscopic machines, molecular-level machines are characterized by (i) the kind of energy input supplied to make them work, (ii) the kind of movement performed by their components, (iii) the way in which their operation can be controlled and monitored, (iv) the possibility to repeat the operation at will and establish a cyclic process, (v) the time scale needed to complete a cycle of operation, and (vi) the function performed. The most convenient way to supply energy to an artificial molecular-level machine is through a photochemical reaction.[Ru(bpy)3]2+(bpy=2,2′-bipyridine) can be used as a photosensitizer to power mechanical movements in machines based on pseudorotaxanes, rotaxanes and catenanes. Besides being used as an external photosensitizer,[Ru(bpy)3]2+can be incorporated in one of the machine components as a "light-fueled" motor. Three types of photochemically driven piston/cylinder systems and a photocontrollable molecular abacus are described. Other kinds of more sophisticated molecular-level machines based on rotaxanes and catenanes are proposed. The extension of the concept of machine to the molecular level is important not only for the sake of basic research, but also for the growth of nanoscience and the development of nanotechnology

An effective 6DoF motion model for 3D-6DoF Monte Carlo Localization

This paper deals with the probabilistic 6DoF motion model of a wheeled road vehicle. It allows to correctly model the error introduced by dead reckoning. Furthermore, to stress the importance of an appropriate motion model, i.e., that different models are not equally good, we show that another model, which was previously developed, does not allow a correct representation of the uncertainty, therefore misguiding 3D-6DoF Monte Carlo Localization. We also present some field experiments to demonstrate that our model allow a consistent determination of the 6DoF vehicle pose

Improved results of the vacuum assisted closure and Nitinol clips sternal closure after postoperative deep sternal wound infection

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Nature-Inspired Nanotechnology and Smart Magnetic Activation: Two Groundbreaking Approaches Toward a New Generation of Biomaterials for Hard Tissue Regeneration

Today, as the need of new regenerative solutions is steadily increasing, the demand for new bio-devices with smart functionality is pushing material scientists to develop new synthesis concepts. Indeed, the conventional approaches for biomaterials fail when it comes to generate nano-biocomposites with designed biomimetic composition and hierarchically organized architecture mimicking biologically relevant tissue features. In this respect, an emerging concept in material science is to draw inspiration from natural processes and products, which we may consider as the most advanced examples of smart nanotechnology. Natural processes of supramolecular assembly and mineralization of organic macromolecules, known as biomineralization, generate complex hybrid 3D constructs that are the basis of skeletons, exoskeletons, nacre and shells. On the other hand, natural structures such as woods and plants exhibit multi-scale hierarchic organization that is the source of smart and anisotropic mechanical properties associated with high porosity and lightness. The association of nature-inspired nano-technological products with smart functionalization can provide new advanced solutions to critical and still unmet clinical needs. In this respect, magnetic activation of biomaterials by the use of a recently developed biocompatible, resorbable magnetic apatite promises to represent a new safe and effective switching tool, enabling personalized applications in regenerative medicine and theranostics that so far were not feasible, due to the cytotoxicity of the currently used magnetic materials

Photoinduced electron flow in a self-assembling supramolecular extension cable

We report the design, bottom-up construction, characterization, and operation of a supramolecular system capable of mimicking the function played by a macroscopic electrical extension cable. The system is made up of a light-powered electron source, an electron drain, and a cable as the molecular components programmed to self-assemble by means of two distinct plug/socket junctions. Such connections are reversible and can be operated independently by orthogonal chemical inputs. In the source-connector-drain supermolecule, photoinduced electron transfer from source to drain occurs, and it can be switched off by dual-mode chemically controlled disassembling of the molecular components.Ferrer Ribera, RB.; Rogez, G.; Credi, A.; Ballardini, R.; Gandolfi, MT.; Balzani, V.; Liu, Y.... (2006). Photoinduced electron flow in a self-assembling supramolecular extension cable. Proceedings of the National Academy of Sciences. 103(49):18411-18416. doi:10.1073/pnas.060645910318411184161034

Pilot Study of the Mechanism of Action of Preoperative Trastuzumab in Patients with Primary Operable Breast Tumors Overexpressing HER2

Abstract Purpose: To elucidate the mechanism by which trastuzumab, a humanized monoclonal antibody against HER2 with proven survival benefit in women with HER2-positive metastatic breast cancer, mediates its antitumor activity. Experimental Design: A pilot study including 11 patients with HER2-positive tumors treated in a neo-adjuvant setting with trastuzumab was performed. Trastuzumab was administered i.v. at a dose of 4 mg/kg followed by three weekly i.v. doses of 2 mg/kg. The primary tumor was surgically removed 7 days after the last treatment. Surgical samples, tumor biopsies, and lymphocytes from these patients were collected for biological studies. Result: Clinical data indicated one complete pathological remission and four partial remissions using RECIST (Response Evaluation Criteria in Solid Tumors). Trastuzumab was well tolerated and neither serious adverse events nor changes in cardiac function were observed during this short-term treatment and after surgery. The biological data showed that, independent of response, (a) all patients showed high levels of circulating trastuzumab; (b) saturating level of trastuzumab was present in all of the tumors; (c) no down-modulation of HER2 was observed in any tumors; (d) no changes in vessel diameter was observed in any tumors; (e) no changes in proliferation was observed in any tumors; and (f) a strong infiltration by lymphoid cells was observed in all cases. Patients with complete remission or partial remission were found to have a higher in situ infiltration of leukocytes and a higher capability to mediate in vitro antibody-dependent cellular cytotoxicity activity. Conclusions: The results of this pilot study argue against trastuzumab activity in patients through down-modulation of HER2 but in favor of antibody-dependent cellular cytotoxicity guiding efforts to optimize the use of trastuzumab in breast cancer patients

Factors Associated With Severe Gastrointestinal Diagnoses in Children With SARS-CoV-2 Infection or Multisystem Inflammatory Syndrome

Importance Severe gastrointestinal (GI) manifestations have been sporadically reported in children with COVID-19; however, their frequency and clinical outcome are unknown. Objective To describe the clinical, radiological, and histopathologic characteristics of children with COVID-19 presenting with severe GI manifestations to identify factors associated with a severe outcome. Design, Setting, and Participants A multicenter retrospective cohort study (February 25, 2020, to January 20, 2021) enrolled inpatient and outpatient children (aged <18 years) with acute SARS-CoV-2 infection, confirmed by positive real-time reverse-transcriptase–polymerase chain reaction on nasopharyngeal swab or fulfilling the US Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children (MIS-C). The study was conducted by pediatricians working in primary care or hospitals in Italy participating in the COVID-19 Registry of the Italian Society of Pediatric Infectious Diseases. Main Outcomes and Measures The occurrence of severe GI manifestations, defined by a medical and/or radiological diagnosis of acute abdomen, appendicitis (complicated or not by perforation and/or peritonitis), intussusception, pancreatitis, abdominal fluid collection, and diffuse adenomesenteritis requiring surgical consultation, occurring during or within 4 to 6 weeks after infection with SARS-CoV-2 infection. Logistic regression was used to estimate odds ratios (ORs) with 95% CIs of factors potentially associated with severe outcomes. Results Overall, 685 children (386 boys [56.4%]; median age, 7.3 [IQR, 1.6-12.4] years) were included. Of these children, 628 (91.7%) were diagnosed with acute SARS-CoV-2 infection and 57 (8.3%) with MIS-C. The presence of GI symptoms was associated with a higher chance of hospitalization (OR, 2.64; 95% CI, 1.89-3.69) and intensive care unit admission (OR, 3.90; 95% CI, 1.98–7.68). Overall, 65 children (9.5%) showed severe GI involvement, including disseminated adenomesenteritis (39.6%), appendicitis (33.5%), abdominal fluid collection (21.3%), pancreatitis (6.9%), or intussusception (4.6%). Twenty-seven of these 65 children (41.5%) underwent surgery. Severe GI manifestations were associated with the child’s age (5-10 years: OR, 8.33; 95% CI, 2.62-26.5; >10 years: OR, 6.37; 95% CI, 2.12-19.1, compared with preschool-age), abdominal pain (adjusted OR [aOR], 34.5; 95% CI, 10.1-118), lymphopenia (aOR, 8.93; 95% CI, 3.03-26.3), or MIS-C (aOR, 6.28; 95% CI, 1.92-20.5). Diarrhea was associated with a higher chance of adenomesenteritis (aOR, 3.13; 95% CI, 1.08-9.12) or abdominal fluid collection (aOR, 3.22; 95% CI, 1.03-10.0). Conclusions and Relevance In this multicenter cohort study of Italian children with SARS-CoV-2 infection or MIS-C, 9.5% of the children had severe GI involvement, frequently associated with MIS-C. These findings suggest that prompt identification may improve the management of serious complications

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered