A VISCOELASTOPLASTIC MODEL TO INTERPRET DENTAL CEMENTS RESPONSE TO A NANOINDENTATION TEST

Nowadays employment of dental resins of different types has become a standard procedure. Providing a complete characterization of their mechanical behaviour is mandatory to improve their characteristics, design, and usage. In this study, we applied the nanoindentation technique to obtain experimental data to be fitted. Then, a genetic algorithm combined with a gradient algorithm were applied to find the best set of the mechanical parameters that characterize the Burger model in series with a frictional element, able to predict the nanoindentation process. Furthermore, with this approach one type of test permits to obtain mechanical parameters useful to characterize the viscoelastoplastic response of these materials

Multiscale Characterization of Isotropic Pyrolytic Carbon Used for Mechanical Heart Valve Production

Usage of pyrolytic carbon (PyC) to produce mechanical heart valves (MHVs) has led to heart valve replacement being a very successful procedure. Thus, the mechanical properties of employed materials for MHV production are fundamental to obtain the required characteristics of biocompatibility and wear resistance. In this study, two deposition methods of PyC were compared through a multiscale approach, performing three-point bending tests and nanoindentation tests. Adopted deposition processes produced materials that were slightly different. Significant differences were found at the characteristic scale lengths of the deposited layers. Setting changes of the deposition process permitted obtaining PyC characterized by a more uniform microstructure, conferring to the bulk material superior mechanical properties

COLLAGEN CROSS-LINKER EFFECT ON THE MECHANICAL PROPERTIES OF THE RADICULAR HYBRID LAYER IN RESTORATIVE DENTISTRY: A NANOINDENTATION STUDY

Bond strength between the dentin and the restorative resins is deeply dependent on the nature of their interface. Resins impregnate dentin, which is rich in collagen fibers. This in vitro study aimed to evaluate the effect of collagen carbodiimide cross linker agent (EDC) on the mechanical properties of the adhesive interface in endodontically treated teeth. Twenty upper premolar teeth were selected and divided into two groups according to the dentin pretreatment procedures: no EDC application (group A) and EDC application (group B). Three typical zones, i.e. the dentin, the radicular hybrid layer and the resin, were analyzed using a Nanoindenter XP equipped with a diamond Berkovich indenter. The input curve was characterized by loading and unloading phases with a strain rate value of 0.1 s-1 and, an intermediate dumbbell phase of 30 s. The maximum indentation depth was set to be 200 nm. The load-displacement curves were analyzed by using the “Oliver and Pharr” method. The mean values of nanoindentation modulus were determined for the dentin, the radicular hybrid layer and the resin for both the samples with and without crosslinker. In general, the application of EDC was found to modify the mechanical properties of the radicular hybrid layer. The mechanical properties of the radicular hybrid layer could be related to the efficient infiltration of the adhesive systems and collagen crosslinker through dentin

A METHODOLOGICAL APPROACH TO INTERPRET AND COMPARE THE VISCOELASTIC BEHAVIOR OF BIOLOGICAL TISSUES AND HYDROGELS

Cell behavior is strongly influenced by the physical properties of the microenvironment and complex mechanotransduction mechanisms are involved in cell and tissue development, homeostasis and even pathologies. Thus, when developing materials mimicking the extracellular matrix of healthy or pathological tissues their mechanical features should be closely considered. In this context, nanoindentation is a powerful technique for mechanically characterizing biomaterials and hydrogels at the cell-length scale, however, standardized experimental protocols and data analysis techniques are lacking. Here, we propose a methodological approach for quantitatively analyzing and comparing the time-dependent mechanical responses of different samples. As an explanatory study, stress-relaxation nanoindentation tests were performed on human and pig lung samples and on hydrogels in order to quantify and compare their viscoelastic properties

Compact and tunable stretch bioreactor advancing tissue engineering implementation. Application to engineered cardiac constructs

Physical stimuli are crucial for the structural and functional maturation of tissues both in vivo and in vitro . In tissue engineering applications, bioreactors have become fundamental and effective tools for provid- ing biomimetic culture conditions that recapitulate the native physical stimuli. In addition, bioreactors play a key role in assuring strict control, automation, and standardization in the production process of cell-based products for future clinical application. In this study, a compact, easy-to-use, tunable stretch bioreactor is proposed. Based on customizable and low-cost technological solutions, the bioreactor was designed for providing tunable mechanical stretch for biomimetic dynamic culture of different engineered tissues. In-house validation tests demonstrated the accuracy and repeatability of the imposed mechanical stimulation. Proof of concepts biological tests performed on engineered cardiac constructs, based on de- cellularized human skin scaffolds seeded with human cardiac progenitor cells, confirmed the bioreactor Good Laboratory Practice compliance and ease of use, and the effectiveness of the delivered cyclic stretch stimulation on the cardiac construct maturation

Decellularized Human Dermal Matrix as a Biological Scaffold for Cardiac Repair and Regeneration.

The complex and highly organized environment in which cells reside consists primarily of the extracellular matrix (ECM) that delivers biological signals and physical stimuli to resident cells. In the native myocardium, the ECM contributes to both heart compliance and cardiomyocyte maturation and function. Thus, myocardium regeneration cannot be accomplished if cardiac ECM is not restored. We hypothesize that decellularized human skin might make an easily accessible and viable alternate biological scaffold for cardiac tissue engineering (CTE). To test our hypothesis, we decellularized specimens of both human skin and human myocardium and analyzed and compared their composition by histological methods and quantitative assays. Decellularized dermal matrix was then cut into 600-mm-thick sections and either tested by uniaxial tensile stretching to characterize its mechanical behavior or used as three-dimensional scaffold to assess its capability to support regeneration by resident cardiac progenitor cells (hCPCs) in vitro. Histological and quantitative analyses of the dermal matrix provided evidence of both effective decellularization with preserved tissue architecture and retention of ECM proteins and growth factors typical of cardiac matrix. Further, the elastic modulus of the dermal matrix resulted comparable with that reported in literature for the human myocardium and, when tested in vitro, dermal matrix resulted a comfortable and protective substrate promoting and supporting hCPC engraftment, survival and cardiomyogenic potential. Our study provides compelling evidence that dermal matrix holds promise as a fully autologous and cost-effective biological scaffold for CTE

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project

MECHANICAL CHARACTERIZATION OF MATERIALS AND NANO-DEVICESO F BIOMEDICAL INTEREST THROUGH NANOINDENTATION TEST

The nanoindentation technique, known also as instrumented indentation, has been widely accepted as a tool for the mechanical characterization of dental cement composites, and micro-devices as polymeric microspheres. The common thread through these two field is the characteristic magnitude of forces and displacements. The only method to characterize the mechanical behavior of microspheres is the nanoindentaiton, due to their reduced size. On the other side the cements used in dentistry are applied in thin films between a metallic support and the prosthetic crown. However, static protocols that have been developed for metals or alloys, neglecting the viscous nature of these composites, are currently adopted in a very large body of literature. In this study we (1) investigate how the viscous nature of dental composites could corrupt nanoindentation tests, and (2) identify an appropriate protocol that reduces the influence of the viscous, time dependent phenomenon during nanoindentation. Here three different commercial dental cements were tested: Harvard, Telio C.S and, Temp Bond. Static and quasi-static tests were performed. The creep data recorded during the hold phase of the static tests were fit with the Burgers model, by adding a slider. Static tests highlighted the viscoelastoplastic nature of cement composites, indicating a strong correlation between the strain rate imposed during the loading phase and the creep rate recorded in the hold phase. The experiments revealed that the viscous effect can be markedly minimized by applying the quasi-static approach. In this study we proposed a nanoindentation-based, quasi-static approach to minimize viscous effects of dental cement composites. In particular, it was demonstrated that the proposed approach is effective in minimizing the time-dependent phenomena during the unloading phase of the test. Moreover, a viscoelatoplastic model(accounting for nanoindentation test size-dependent output) wassuccessfully adopted to fit the experimental data. This model in now suitable for computer aided simulations of the indentation process making it possible to evaluate at which level viscous phenomena could affect the estimation of the contact area. Polymeric microspheres are largely studied for biomedical applications as, e.g., embolic agents to treat hyper-vascular tumors, or in tissue engineering. The rationale of the study is understand how the used polymers and the presence of the cross-linker influence the mechanical properties of the microspheres and therefore the effectiveness in properly release drugs. The composition of the polymeric microspheres, influences only their mechanical properties. Drug release experiments, performed by using methylene blue clearly indicate that the time course of the release of the therapeutic agent strongly depends on the used polymer(s). blending natural polymers and adding genipin as natural cross-linker could lead the production of natural microspheres with adjustable mechanical properties, suitable for drug transport and delivery. Technically, nanoindentation was applied on microspheres of size in the range 20-70 μm. The mechanical characterization highlighted a viscous-elastic behavior of microspheres, with an increasing area of the characteristics hysteresis loops when the genipin concentration increases. Moreover, on measured load-displacement data, the Hertz model was applied to estimate the Young’s modulus. A protocol for the mechanical characterization of polymeric microspheres used for drug delivery will allow: (1) to support their design phase and (2) to improve their effectiveness in targeting the release of drugs

Static Mechanical Characterization of Cements for Dental Implantology through Nanoindentation

The nanoindentation technique has become very popular in the field of mechanical testing of materials for biomedical applications, due to the punctually of the test, the reduced quantity of material required and the possibility of testing soft materials . This technique has been used in this work with the purpose of identifying the mechanical properties of cements for dental implantology. Three cements were characterized. For all the samples the same input curve was applied. The experimental plan considered three factors: the cement type, the loading rate and the indentation depth. On samples, the Young's Modulus and Hardness were calculated by applying the Oliver and Pharr Method. The mechanical properties were subsequently compared through multivariate analysis of variance (ANOVA). Results confirmed the higher mechanical properties of permanent cements compared with temporary ones, also highlighting a viscous-plastic behavior for all the cements analyzed