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3. Magnesium Alloys in Orthopedics: A Systematic Review on Approaches, Coatings and Strategies to Improve Biocompatibility, Osteogenic Properties and Osteointegration Capabilities

Author

Giavaresi, Gianluca, primary, Bellavia, Daniele, additional, De Luca, Angela De, additional, Costa, Viviana, additional, Raimondi, Lavinia, additional, Cordaro, Aurora, additional, Sartori, Maria, additional, Terrando, Silvio, additional, Toscano, Angelo, additional, Pignatti, Giovanni, additional, and Fini, Milena, additional

Published
2023
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9. Bactericidal Activity of Silver-Doped Chitosan Coatings via Electrophoretic Deposition on Ti6Al4V Additively Manufactured Substrates

Author

Ghalayani Esfahani, Arash, primary, Sartori, Maria, additional, Bregoli, Chiara, additional, Fiocchi, Jacopo, additional, Biffi, Carlo Alberto, additional, Tuissi, Ausonio, additional, Giavaresi, Gianluca, additional, Presentato, Alessandro, additional, Alduina, Rosa, additional, De Luca, Angela, additional, Cabrini, Alessia, additional, De Capitani, Cristina, additional, Fini, Milena, additional, Gruppioni, Emanuele, additional, Lavorgna, Marino, additional, and Ronca, Alfredo, additional

Published
2023
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10. Human Osteoblasts’ Response to Biomaterials for Subchondral Bone Regeneration in Standard and Aggressive Environments

Author

Pagani, Stefania, primary, Salerno, Manuela, additional, Filardo, Giuseppe, additional, Locs, Janis, additional, van Osch, Gerjo J.V.M., additional, Vecstaudza, Jana, additional, Dolcini, Laura, additional, Borsari, Veronica, additional, Fini, Milena, additional, Giavaresi, Gianluca, additional, and Columbaro, Marta, additional

Published
2023
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17. Complications after Posterior Lumbar Fusion for Degenerative Disc Disease: Sarcopenia and Osteopenia as Independent Risk Factors for Infection and Proximal Junctional Disease

Author

Ruffilli, Alberto, primary, Manzetti, Marco, additional, Barile, Francesca, additional, Ialuna, Marco, additional, Cerasoli, Tosca, additional, Viroli, Giovanni, additional, Salamanna, Francesca, additional, Contartese, Deyanira, additional, Giavaresi, Gianluca, additional, and Faldini, Cesare, additional

Published
2023
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18. Knee Joint Contact Forces during High-Risk Dynamic Tasks: 90° Change of Direction and Deceleration Movements

Author

Cassiolas, Giorgio, primary, Di Paolo, Stefano, additional, Marchiori, Gregorio, additional, Grassi, Alberto, additional, Della Villa, Francesco, additional, Bragonzoni, Laura, additional, Visani, Andrea, additional, Giavaresi, Gianluca, additional, Fini, Milena, additional, Zaffagnini, Stefano, additional, and Lopomo, Nicola Francesco, additional

Published
2023
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22. Bone Regeneration Guided by a Magnetized Scaffold in an Ovine Defect Model

Author

Maglio, Melania, primary, Sartori, Maria, additional, Gambardella, Alessandro, additional, Shelyakova, Tatiana, additional, Dediu, Valentin Alek, additional, Santin, Matteo, additional, Piñeiro, Yolanda, additional, López, Manuel Bañobre, additional, Rivas, Josè, additional, Tampieri, Anna, additional, Sprio, Simone, additional, Martini, Lucia, additional, Gatti, Alessandro, additional, Russo, Alessandro, additional, Giavaresi, Gianluca, additional, and Fini, Milena, additional

Published
2023
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26. Potential Anti-Metastatic Role of the Novel miR-CT3 in Tumor Angiogenesis and Osteosarcoma Invasion

Author

Raimondi, Lavinia, primary, Gallo, Alessia, additional, Cuscino, Nicola, additional, De Luca, Angela, additional, Costa, Viviana, additional, Carina, Valeria, additional, Bellavia, Daniele, additional, Bulati, Matteo, additional, Alessandro, Riccardo, additional, Fini, Milena, additional, Conaldi, Pier Giulio, additional, and Giavaresi, Gianluca, additional

Published
2022
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28. Preliminary Results of CitraVes™ Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study

Author

Raimondo, Stefania, primary, Nikolic, Dragana, additional, Conigliaro, Alice, additional, Giavaresi, Gianluca, additional, Lo Sasso, Bruna, additional, Giglio, Rosaria Vincenza, additional, Chianetta, Roberta, additional, Manno, Mauro, additional, Raccosta, Samuele, additional, Corleone, Valeria, additional, Ferrante, Giovanni, additional, Citarrella, Roberto, additional, Rizzo, Manfredi, additional, De Leo, Giacomo, additional, Ciaccio, Marcello, additional, Montalto, Giuseppe, additional, and Alessandro, Riccardo, additional

Published
2021
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29. How miR-31-5p and miR-33a-5p Regulates SP1/CX43 Expression in Osteoarthritis Disease: Preliminary Insights

Author

Costa, Viviana, primary, De Fine, Marcello, additional, Carina, Valeria, additional, Conigliaro, Alice, additional, Raimondi, Lavinia, additional, De Luca, Angela, additional, Bellavia, Daniele, additional, Salamanna, Francesca, additional, Alessandro, Riccardo, additional, Pignatti, Giovanni, additional, Fini, Milena, additional, and Giavaresi, Gianluca, additional

Published
2021
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30. Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology

Author

Raimondi, Lavinia, primary, De Luca, Angela, additional, Giavaresi, Gianluca, additional, Raimondo, Stefania, additional, Gallo, Alessia, additional, Taiana, Elisa, additional, Alessandro, Riccardo, additional, Rossi, Marco, additional, Neri, Antonino, additional, Viglietto, Giuseppe, additional, and Amodio, Nicola, additional

Published
2020
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31. Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis

Author

Raimondi, Lavinia, primary, De Luca, Angela, additional, Fontana, Simona, additional, Amodio, Nicola, additional, Costa, Viviana, additional, Carina, Valeria, additional, Bellavia, Daniele, additional, Raimondo, Stefania, additional, Siragusa, Sergio, additional, Monteleone, Francesca, additional, Alessandro, Riccardo, additional, Fini, Milena, additional, and Giavaresi, Gianluca, additional

Published
2020
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33. Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma

Author

Raimondo, Stefania, primary, Urzì, Ornella, additional, Conigliaro, Alice, additional, Lo Bosco, Giosuè, additional, Parisi, Sofia, additional, Carlisi, Melania, additional, Siragusa, Sergio, additional, Raimondi, Lavinia, additional, De Luca, Angela, additional, Giavaresi, Gianluca, additional, and Alessandro, Riccardo, additional

Published
2020
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34. The Non-Coding RNA Landscape of Plasma Cell Dyscrasias

Author

Morelli, Eugenio, primary, Gullà, Annamaria, additional, Rocca, Roberta, additional, Federico, Cinzia, additional, Raimondi, Lavinia, additional, Malvestiti, Stefano, additional, Agosti, Valter, additional, Rossi, Marco, additional, Costa, Giosuè, additional, Giavaresi, Gianluca, additional, Azab, Abdel Kareem, additional, Cagnetta, Antonia, additional, Cea, Michele, additional, Tagliaferri, Pierosandro, additional, Neri, Antonino, additional, Munshi, Nikhil C., additional, Viglietto, Giuseppe, additional, Tassone, Pierfrancesco, additional, and Amodio, Nicola, additional

Published
2020
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38. Regenerative Features of Adipose Tissue for Osteoarthritis Treatment in a Rabbit Model: Enzymatic Digestion Versus Mechanical Disruption

Author

Desando, Giovanna, primary, Bartolotti, Isabella, additional, Martini, Lucia, additional, Giavaresi, Gianluca, additional, Nicoli Aldini, Nicolò, additional, Fini, Milena, additional, Roffi, Alice, additional, Perdisa, Francesco, additional, Filardo, Giuseppe, additional, Kon, Elizaveta, additional, and Grigolo, Brunella, additional

Published
2019
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41. Adjuvant Biophysical Therapies in Osteosarcoma

Author

Carina, Valeria, primary, Costa, Viviana, additional, Sartori, Maria, additional, Bellavia, Daniele, additional, De Luca, Angela, additional, Raimondi, Lavinia, additional, Fini, Milena, additional, and Giavaresi, Gianluca, additional

Published
2019
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43. Complications after Posterior Lumbar Fusion for Degenerative Disc Disease: Sarcopenia and Osteopenia as Independent Risk Factors for Infection and Proximal Junctional Disease

Author

Alberto Ruffilli, Marco Manzetti, Francesca Barile, Marco Ialuna, Tosca Cerasoli, Giovanni Viroli, Francesca Salamanna, Deyanira Contartese, Gianluca Giavaresi, Cesare Faldini, Ruffilli, Alberto, Manzetti, Marco, Barile, Francesca, Ialuna, Marco, Cerasoli, Tosca, Viroli, Giovanni, Salamanna, Francesca, Contartese, Deyanira, Giavaresi, Gianluca, and Faldini, Cesare

Subjects
sarcopenia, spine surgery, osteopenia, risk factor, complications, degenerative disc disease, lumbar spine, risk factors, complication, General Medicine
Abstract

Proximal Junctional Disease (PJD) and Surgical Site Infection (SSI) are among the most common complications following spine surgery. Their risk factors are not fully understood. Among them, sarcopenia and osteopenia have recently been attracting interest. The aim of this study is to evaluate their influence on mechanical or infective complications after lumbar spine fusion. Patients who underwent open posterior lumbar fusion were analyzed. Through preoperative MRI, central sarcopenia and osteopenia were measured with the Psoas Lumbar Vertebral Index (PLVI) and the M-Score, respectively. Patients were stratified by low vs. high PLVI and M-Score and then by postoperative complications. Multivariate analysis for independent risk factors was performed. A total of 392 patients (mean age 62.6 years, mean follow up 42.4 months) were included. Multivariate linear regression identified comorbidity Index (p = 0.006), and dural tear (p = 0.016) as independent risk factors for SSI, and age (p = 0.014) and diabetes (p = 0.43) for PJD. Low M-score and PLVI were not correlated to a higher complications rate. Age, comorbidity index, diabetes, dural tear and length of stay are independent risk factors for infection and/or proximal junctional disease in patients who undergo lumbar arthrodesis for degenerative disc disease, while central sarcopenia and osteopenia (as measured by PLVI and M-score) are not.

Published
2023

44. The Binomial 'Inflammation-Epigenetics' in Breast Cancer Progression and Bone Metastasis: IL-1β Actions Are Influenced by TET Inhibitor in MCF-7 Cell Line

Author

Daniele Bellavia, Viviana Costa, Angela De Luca, Aurora Cordaro, Milena Fini, Gianluca Giavaresi, Fabio Caradonna, Lavinia Raimondi, Bellavia, Daniele, Costa, Viviana, De Luca, Angela, Cordaro, Aurora, Fini, Milena, Giavaresi, Gianluca, Caradonna, Fabio, and Raimondi, Lavinia

Subjects
Epithelial-Mesenchymal Transition, DNA methylation, bone metastasis, inflammation, Interleukin-1β, ten-eleven translocation proteins, MCF-7 cell line, Interleukin-1beta, Breast Neoplasms, Bone Neoplasms, Catalysis, Epigenesis, Genetic, Inorganic Chemistry, Settore BIO/13 - Biologia Applicata, Cell Line, Tumor, Humans, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Organic Chemistry, General Medicine, Computer Science Applications, Settore BIO/18 - Genetica, MCF-7 Cells, Female, Inflammatory Breast Neoplasms
Abstract

The existence of a tight relationship between inflammation and epigenetics that in primary breast tumor cells can lead to tumor progression and the formation of bone metastases was investigated. It was highlighted how the induction of tumor progression and bone metastasis by Interleukin-1 beta, in a non-metastatic breast cancer cell line, MCF-7, was dependent on the de-methylating actions of ten-eleven translocation proteins (TETs). In fact, the inhibition of their activity by the Bobcat339 molecule, an inhibitor of TET enzymes, determined on the one hand, the modulation of the epithelial-mesenchymal transition process, and on the other hand, the reduction in the expression of markers of bone metastasis, indicating that the epigenetic action of TETs is a prerequisite for IL-1β-dependent tumor progression and bone metastasis formation.

Published
2022

45. Potential Anti-Metastatic Role of the Novel miR-CT3 in Tumor Angiogenesis and Osteosarcoma Invasion

Author

Lavinia Raimondi, Alessia Gallo, Nicola Cuscino, Angela De Luca, Viviana Costa, Valeria Carina, Daniele Bellavia, Matteo Bulati, Riccardo Alessandro, Milena Fini, Pier Giulio Conaldi, Gianluca Giavaresi, Raimondi, Lavinia, Gallo, Alessia, Cuscino, Nicola, De Luca, Angela, Costa, Viviana, Carina, Valeria, Bellavia, Daniele, Bulati, Matteo, Alessandro, Riccardo, Fini, Milena, Conaldi, Pier Giulio, and Giavaresi, Gianluca

Subjects
Epithelial-Mesenchymal Transition, QH301-705.5, MAP Kinase Signaling System, EMT protein, Bone Neoplasms, Article, Catalysis, Cell Line, Inorganic Chemistry, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, metastasis, Humans, Neoplasm Invasiveness, Biology (General), Physical and Theoretical Chemistry, QD1-999, Molecular Biology, Spectroscopy, Osteosarcoma, Osteoblasts, microRNA, Neovascularization, Pathologic, Organic Chemistry, EMT proteins, tumor angiogenesis, General Medicine, microRNAs, Computer Science Applications, Gene Expression Regulation, Neoplastic, Chemistry, osteosarcoma, metastasi, tumor angiogenesi
Abstract

Osteosarcoma (OS) is the most common primary bone tumor mainly occurring in young adults and derived from primitive bone-forming mesenchyme. OS develops in an intricate tumor microenvironment (TME) where cellular function regulated by microRNAs (miRNAs) may affect communication between OS cells and the surrounding TME. Therefore, miRNAs are considered potential therapeutic targets in cancer and one of the goals of research is to accurately define a specific signature of a miRNAs, which could reflect the phenotype of a particular tumor, such as OS. Through NGS approach, we previously found a specific molecular profile of miRNAs in OS and discovered 8 novel miRNAs. Among these, we deepen our knowledge on the fifth candidate renamed now miR-CT3. MiR-CT3 expression was low in OS cells when compared with human primary osteoblasts and healthy bone. Through TargetScan, VEGF-A was predicted as a potential biological target of miR-CT3 and luciferase assay confirmed it. We showed that enforced expression of miR-CT3 in two OS cell lines, SAOS-2 and MG-63, reduced expression of VEGF-A mRNA and protein, inhibiting tumor angiogenesis. Enforced expression of miR-CT3 also reduced OS cell migration and invasion as confirmed by soft agar colony formation assay. Interestingly, we found that miR-CT3 behaves inducing the activation of p38 MAP kinase pathway and modulating the epithelial-mesenchymal transition (EMT) proteins, in particular reducing Vimentin expression. Overall, our study highlights the novel role of miR-CT3 in regulating tumor angiogenesis and progression in OS cells, linking also to the modulation of EMT proteins.

Published
2022

46. Platelet and Lymphocyte-Related Parameters as Potential Markers of Osteoarthritis Severity: A Cross-Sectional Study.

Author

Salamanna F, Pagani S, Filardo G, Contartese D, Boffa A, Angelelli L, Maglio M, Fini M, Zaffagnini S, and Giavaresi G

Abstract

Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering age, sex, and body mass index (BMI)., Methods: Patients aged ≥40 years were included in this cross-sectional study and divided into groups based on knee OA severity using the Kellgren-Lawrence (KL) grading system. A logistic regression model, adjusted for confounders, evaluated the ability of PLT, MPV, LINF, and PLR to categorize OA severity. Model performance in terms of accuracy, sensitivity, and specificity was assessed using ROC curves., Results: The study involved 245 OA patients (51.4% female, 48.6% male) aged 40-90 years, 35.9% with early OA (KL < 3) and 64.1% moderate/severe OA (KL ≥ 3). Most patients (60.8%) were aged ≥60 years, and BMI was <25 kg/m 2 in 33.9%. The model showed that a 25-unit increase in PLR elevates the odds of higher OA levels by 1.30 times (1-unit OR = 1.011, 95% CI [1.004, 1.017], p < 0.005), while being ≥40 years old elevates the odds by 4.42 times (OR 4.42, 95% CI [2.46, 7.95], p < 0.0005). The model's accuracy was 73.1%, with 84% sensitivity, 52% specificity, and an AUC of 0.74 (95% CI [0.675, 0.805])., Conclusions: Higher PLR increases the likelihood of moderate/severe OA, suggesting that monitoring these biomarkers could aid in early detection and management of OA severity. Further research is warranted to cross-validate these results in larger populations.

Published
2024
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47. Understanding the Structure-Function Relationship through 3D Imaging and Biomechanical Analysis: A Novel Methodological Approach Applied to Anterior Cruciate Ligaments.

Author

Bontempi M, Sancisi N, Marchiori G, Conconi M, Berni M, Cassiolas G, Giavaresi G, Parrilli A, and Lopomo NF

Abstract

Understanding the microstructure of fibrous tissues, like ligaments, is crucial due to their nonlinear stress-strain behavior from unique fiber arrangements. This study introduces a new method to analyze the relationship between the microstructure and function of anterior cruciate ligaments (ACL). We tested the procedure on two ACL samples, one from a healthy individual and one from an osteoarthritis patient, using a custom tensioning device within a micro-CT scanner. The samples were stretched and scanned at various strain levels (namely 0%, 1%, 2%, 3%, 4%, 6%, 8%) to observe the effects of mechanical stress on the microstructure. The micro-CT images were processed to identify and map fibers, assessing their orientations and volume fractions. A probabilistic mathematical model was then proposed to relate the geometric and structural characteristics of the ACL to its mechanical properties, considering fiber orientation and thickness. Our feasibility test indicated differences in mechanical behavior, fiber orientation, and volume distribution between ligaments of different origins. These indicative results align with existing literature, validating the proposed methodology. However, further research is needed to confirm these preliminary observations. Overall, our comprehensive methodology shows promise for improving ACL diagnosis and treatment and for guiding the creation of tissue-engineered grafts that mimic the natural properties and microstructure of healthy tissue, thereby enhancing integration and performance in biomedical applications.

Published
2024
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48. Regeneration of Osteochondral Lesion of the Talus with Retrograde Drilling Technique: An In Vitro Pilot Study.

Author

Veronesi F, Maglio M, Brogini S, Mazzotti A, Artioli E, Zielli SO, Faldini C, and Giavaresi G

Abstract

Background: Retrograde Drilling (RD) is a surgical technique employed for osteochondral lesions of the talus (OCLTs) to reach the subchondral bone lesion from behind, thus preserving cartilage integrity. The aim of the present pilot study was to set up an in vitro model of OCLTs to evaluate the regenerative potential of biological approaches that could be associated with the RD technique. Methods: For this purpose, an OCLT was created in human osteochondral specimens, to try to mimic the RD technique, and to compare the regenerative potential of two biological treatments. For this purpose, three groups of treatments were performed in vitro: (1) no treatment (empty defect); (2) autologous bone graft (ABG); (3) hyaluronic membrane enriched with autologous bone marrow cells. Tissue viability; production of Collagen I and II, Vascular Endothelial Growth Factor, and Aggrecan; and histological and microCT evaluations were performed after 30 days of culture in normal culture conditions. Results: It was observed that Group 3 showed the highest viability, and Group 2 showed the highest protein production. From a histological and microtomographic point of view, it was possible to appreciate the structure of the morcellized bone with which the defect of Group 2 was filled, while it was not yet possible to observe the deposition of mineralized tissue in Group 3. Conclusions: To conclude, this pilot study shows the feasibility of an alternative in vitro model to evaluate and compare the regenerative potential of two biological scaffolds, trying to mimic the RD technique as much as possible. The tissues remained vital for up to 4 weeks and both ABG and hyaluronic acid-based scaffolds stimulated the release of proteins linked to regenerative processes in comparison to the empty defect group.

Published
2024
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49. Preliminary Evaluation of Bioactive Collagen-Polyphenol Surface Nanolayers on Titanium Implants: An X-ray Photoelectron Spectroscopy and Bone Implant Study.

Author

Morra M, Iviglia G, Cassinelli C, Sartori M, Cavazza L, Martini L, Fini M, and Giavaresi G

Abstract

To endow an implant surface with enhanced properties to ensure an appropriate seal with the host tissue for inflammation/infection resistance, next-generation bone implant collagen-polyphenol nanolayers were built on conventional titanium surfaces through a multilayer approach. X-ray Photoelectron Spectroscopy (XPS) analysis was performed to investigate the chemical arrangement of molecules within the surface layer and to provide an estimate of their thickness. A short-term (2 and 4 weeks) in vivo test of bone implants in a healthy rabbit model was performed to check possible side effects of the soft surface layer on early phases of osteointegration, leading to secondary stability. Results show the building up of the different nanolayers on top of titanium, resulting in a final composite collagen-polyphenol surface and a layer thickness of about 10 nm. In vivo tests performed on machined and state-of-the-art microrough titanium implants do not show significant differences between coated and uncoated samples, as the surface microroughness remains the main driver of bone-to-implant contact. These results confirm that the surface nanolayer does not interfere with the onset and progression of implant osteointegration and prompt the green light for specific investigations of the potential merits of this bioactive coating as an enhancer of the device/tissue seal.

Published
2024
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50. Nanomechanical Mapping of Three Dimensionally Printed Poly-ε-Caprolactone Single Microfibers at the Cell Scale for Bone Tissue Engineering Applications.

Author

Bontempi M, Marchiori G, Petretta M, Capozza R, Grigolo B, Giavaresi G, and Gambardella A

Abstract

Poly-ε-caprolactone (PCL) has been widely used in additive manufacturing for the construction of scaffolds for bone tissue engineering. However, its use is limited by its lack of bioactivity and inability to induce cell adhesion, hence limiting bone tissue regeneration. Biomimicry is strongly influenced by the dynamics of cell-substrate interaction. Thus, characterizing scaffolds at the cell scale could help to better understand the relationship between surface mechanics and biological response. We conducted atomic force microscopy-based nanoindentation on 3D-printed PCL fibers of ~300 µm thickness and mapped the near-surface Young's modulus at loading forces below 50 nN. In this non-disruptive regime, force mapping did not show clear patterns in the spatial distribution of moduli or a relationship with the topographic asperities within a given region. Remarkably, we found that the average modulus increased linearly with the logarithm of the strain rate. Finally, a dependence of the moduli on the history of nanoindentation was demonstrated on locations of repeated nanoindentations, likely due to creep phenomena capable of hindering viscoelasticity. Our findings can contribute to the rational design of scaffolds for bone regeneration that are capable of inducing cell adhesion and proliferation. The methodologies described are potentially applicable to various tissue-engineered biopolymers.

Published
2023
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