Leonardo Vivarelli

Bio: Leonardo Vivarelli is an academic researcher. The author has contributed to research in topics: Medicine & Osteoarthritis. The author has an hindex of 3, co-authored 10 publications receiving 48 citations.

A Comprehensive Microstructural and Compositional Characterization of Allogenic and Xenogenic Bone: Application to Bone Grafts and Nanostructured Biomimetic Coatings

Abstract: Bone grafts and bone-based materials are widely used in orthopedic surgery. However, the selection of the bone type to be used is more focused on the biological properties of bone sources than physico-chemical ones. Moreover, although biogenic sources are increasingly used for deposition of biomimetic nanostructured coatings, the influence of specific precursors used on coating’s morphology and composition has not yet been explored. Therefore, in order to fill this gap, we provided a detailed characterization of the properties of the mineral phase of the most used bone sources for allografts, xenografts and coating deposition protocols, not currently available. To this aim, several bone apatite precursors are compared in terms of composition and morphology. Significant differences are assessed for the magnesium content between female and male human donors, and in terms of Ca/P ratio, magnesium content and carbonate substitution between human bone and different animal bone sources. Prospectively, based on these data, bone from different sources can be used to obtain bone grafts having slightly different properties, depending on the clinical need. Likewise, the suitability of coating-based biomimetic films for specific clinical musculoskeletal application may depend on the type of apatite precursor used, being differently able to tune surface morphology and nanostructuration, as shown in the proof of concepts of thin film manufacturing here presented.

Commercial Bone Grafts Claimed as an Alternative to Autografts: Current Trends for Clinical Applications in Orthopaedics

Abstract: In the last twenty years, due to an increasing medical and market demand for orthopaedic implants, several grafting options have been developed. However, when alternative bone augmentation materials mimicking autografts are searched on the market, commercially available products may be grouped into three main categories: cellular bone matrices, growth factor enhanced bone grafts, and peptide enhanced xeno-hybrid bone grafts. Firstly, to obtain data for this review, the search engines Google and Bing were employed to acquire information from reports or website portfolios of important competitors in the global bone graft market. Secondly, bibliographic databases such as Medline/PubMed, Web of Science, and Scopus were also employed to analyse data from preclinical/clinical studies performed to evaluate the safety and efficacy of each product released on the market. Here, we discuss several products in terms of osteogenic/osteoinductive/osteoconductive properties, safety, efficacy, and side effects, as well as regulatory issues and costs. Although both positive and negative results were reported in clinical applications for each class of products, to date, peptide enhanced xeno-hybrid bone grafts may represent the best choice in terms of risk/benefit ratio. Nevertheless, more prospective and controlled studies are needed before approval for routine clinical use.

Design Techniques to Optimize the Scaffold Performance: Freeze-dried Bone Custom-made Allografts for Maxillary Alveolar Horizontal Ridge Augmentation.

Abstract: The purpose of the current investigation was to evaluate the clinical success of horizontal ridge augmentation in severely atrophic maxilla (Cawood and Howell class IV) using freeze-dried custom made bone harvested from the tibial hemiplateau of cadaver donors, and to analyze the marginal bone level gain prior to dental implant placement at nine months subsequent to bone grafting and before prosthetic rehabilitation. A 52-year-old woman received custom made bone grafts. The patient underwent CT scans two weeks prior and nine months after surgery for graft volume and density analysis. The clinical and radiographic bone observations showed a very low rate of resorption after bone graft and implant placement. The custom-made allograft material was a highly effective modality for restoring the alveolar horizontal ridge, resulting in a reduction of the need to obtain autogenous bone from a secondary site with predictable procedure. Further studies are needed to investigate its behavior at longer time periods.

Randomised, double-blind comparison of a fixed co-formulation of intra-articular polynucleotides and hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis: two-year follow-up.

Abstract: A first-year interim analysis of this two-year study suggested that intra-articular injections of highly purified, natural-origin polynucleotides and hyaluronic acid (HA) as a fixed combination (PNHA) might improve knee function and joint pain more effectively than HA alone in patients with knee osteoarthritis (OA). The purpose of the second-year analysis herein described was to verify whether the first-year interim outcomes persist over the whole two-year period. Randomised, double-blind, HA-controlled clinical trial in 100 knee OA patients (98 randomised, 79 completing the study) in a high-specialisation tertiary care setting. The hypothesised difference of efficacy between PNHA and HA for the original sample size estimate is 20%. Treatment cycle: three intra-articular knee injections of either PNHA or HA, at baseline and weekly for two weeks. Evaluations: Western Ontario and McMaster Universities (WOMAC) score and Knee Society Score (KSS) as, respectively, primary and secondary endpoints, evaluated at baseline and after 2, 6, 12, and 24 months; synovial fluid levels of mediators (at baseline and the end of the treatment cycle). Adverse effects investigated at each control visit. Statistical analysis: Kruskal-Wallis test for independent samples (nonparametric one-way analysis of variance) after correction of means for age, Body Mass Index and Kellgren-Lawrence grade. If significant, pairwise post-hoc Sidak multiple comparisons. KSS total score and KSS pain item: significant improvement in both groups, with significantly more pain improvement in patients treated with PNHA (2-point reduction) than HA (1-point reduction). Both groups experienced significant long-term reductions in WOMAC total scores: significantly stronger in PNHA-treated patients after 24 months with a steady difference of 16% favouring PNHA in WOMAC pain subscore. No clinically significant adverse events in either group. The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment (3 weekly double-blind injections) with polynucleotides (long-acting viscosupplementation properties, chondrocyte activation, pain-relieving properties) in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. PNHA may be elective for viscosupplementation in knee OA patients with fastidious and resistant pain and worsening disease. NCT02417610 . Registration, 15/04/2015. ClinicalTrials.gov database link:

Functional nanocomposites and their potential applications: A review

Abstract: Herein, the review aims to compile some reportable work of researchers carried concerning the use of nanomaterials in the polymeric composites for significant improvements in the properties and to report the application areas of such nanocomposites. Carbon nanotubes, cellulose nanoparticles, titanium dioxide, and other nanoparticles are used in the polymeric composites to enhance their mechanical, electrical, inter-laminar, optical, chemical, electrochemical, electromagnetic shielding, and ballistic properties. Such nanocomposites have a wide range of applications in structural, biomedical, electronics, automobiles, aircraft, oil pipelines, gas pipeline construction, electromagnetic shielding, and protected areas. According to the reported results of researchers, the incorporation of nanomaterials into polymers significantly enhance their properties, which make them able to widen their application areas.

Tendon and Cytokine Marker Expression by Human Bone Marrow Mesenchymal Stem Cells in a Hyaluronate/Poly-Lactic-Co-Glycolic Acid (PLGA)/Fibrin Three-Dimensional (3D) Scaffold.

Abstract: We developed a (three-dimensional) 3D scaffold, we named HY-FIB, incorporating a force-transmission band of braided hyaluronate embedded in a cell localizing fibrin hydrogel and poly-lactic-co-glycolic acid (PLGA) nanocarriers as transient components for growth factor controlled delivery. The tenogenic supporting capacity of HY-FIB on human-Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) was explored under static conditions and under bioreactor-induced cyclic strain conditions. HY-FIB elasticity enabled to deliver a mean shear stress of 0.09 Pa for 4 h/day. Tendon and cytokine marker expression by hBM-MSCs were studied. Results: hBM-MSCs embedded in HY-FIB and subjected to mechanical stimulation, resulted in a typical tenogenic phenotype, as indicated by type 1 Collagen fiber immunofluorescence. RT-qPCR showed an increase of type 1 Collagen, scleraxis, and decorin gene expression (3-fold, 1600-fold, and 3-fold, respectively, at day 11) in dynamic conditions. Cells also showed pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokine gene expressions, with a significant increase of anti-inflammatory cytokines in dynamic conditions (IL-10 and TGF-β1 300-fold and 4-fold, respectively, at day 11). Mechanical signaling, conveyed by HY-FIB to hBM-MSCs, promoted tenogenic gene markers expression and a pro-repair cytokine balance. The results provide strong evidence in support of the HY-FIB system and its interaction with cells and its potential for use as a predictive in vitro model.

A critical review on functionally graded coatings: Methods, properties, and challenges

Abstract: Surface coating on metal substrates has remained a difficult challenge for researchers due to the conflicting requirements for different properties. In recent years, due to their mechanical, thermal, electrical, and tribological properties in many advanced engineering applications, functionally graded coatings (FGCs) have become fascinating materials for researchers worldwide to obtain coatings with specific requirements. FGCs are a novel type of traditional composites in which phases are not equally distributed to form a smooth gradient structure; thus, gradient coatings have shown a new research path. Therefore, this paper critically reviews the different FGC processing techniques by describing the fundamental problems and potential of these processes based on existing literature. Additionally, this research presents the most important potential applications and future challenges for gradient coatings. Consequently, the results expected from the paper are considered a guideline that enables the interested in this field to make informed decisions.