Cynthia Secchieri

Fidia Farmaceutici (Italy)

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Co-Authors

Devis Galesso

Fidia Farmaceutici (Italy)

Lawrence J. Bonassar

Cornell University

Edward D. Bonnevie

University of Pennsylvania

Elizabeth Feeney

Duke University

Roberta Ramonda

University of Padua

Itai Cohen

Cornell University

M. Pavan

Fidia Farmaceutici (Italy)

Annalucia Serafino

National Research Council

Lisa A. Fortier

American Veterinary Medical Association

Rossana Psaila

National Academies of Sciences, Engineering, and Medicine

Cooperative Institutions

Fidia Farmaceutici (Italy)

Cornell University

National Research Council

Istituti di Ricovero e Cura a Carattere Scientifico

Istituto di Farmacologia Traslazionale

University of Padua

University of Rome Tor Vergata

National Academies of Sciences, Engineering, and Medicine

Universidad de Granada

University of Milan

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Distinct tribological endotypes of pathological human synovial fluid reveal characteristic biomarkers and variation in efficacy of viscosupplementation at reducing local strains in articular cartilage

Osteoarthritis and Cartilage (2020)

Rebecca M. Irwin Elizabeth Feeney Cynthia Secchieri Devis Galesso Itai Cohen

Viscosupplementation

10.1016/j.joca.2020.02.029

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Citations (15)

Short-Term Homing of Hyaluronan-Primed Cells: Therapeutic Implications for Osteoarthritis Treatment

Tissue Engineering Part C Methods (2017)

Giovanna Desando Isabella Bartolotti Carola Cavallo Antonella Schiavinato Cynthia Secchieri

The evaluation of key factors modulating cell homing following injection can provide new insights in the comprehension of unsolved biological questions about the use of cell therapies for osteoarthritis (OA). The main purpose of this in vivo study was to investigate the biodistribution of an intra-articular injection of mesenchymal stromal cells (MSCs) and bone marrow concentrate (BMC) in a rabbit OA model and whether the additional use of sodium hyaluronate (HA) could modulate their migration and delay joint degeneration. OA was surgically induced in adult male New Zealand rabbits. A group of animals was used to test the biodistribution of labeled cells alone or with HA at 7 and 14 days to investigate cell migration. The efficacy of treatments was evaluated in other experimental groups at 2 months. Histology and immunohistochemistry for markers identifying anabolic and catabolic processes in the cartilage and meniscus, or macrophage subset population in the synovial membrane, were performed. Kruskal-Wallis test, followed by post hoc Dunn's test, and Spearman's rank-order correlation method were used. MSCs and BMC preferentially migrate toward tissue areas showing OA features in the meniscus and cartilage and in detail near inflammatory zones in the synovial membrane. The combination with HA contributed to boost cell migration toward articular cartilage. In general, both labeled cells combined with HA were found near cell cluster and fissures in the cartilage and meniscus, respectively, and close to areas of synovial membrane showing mainly anti-inflammatory macrophages. A promotion of joint repair was observed at different levels for all treatments, although BMC-HA treatment resulted as the best strategy to support joint repair. This last, displayed a good protein expression of type II collagen in the cartilage, as well as the presence of anti-inflammatory macrophages in the synovial membrane at 2 months from the treatment. Studies tracking cell biodistribution indicate that priming progenitor cells with HA modulated cell homing favoring not only attachment but also their integration within articular cartilage.

Homing (biology)

10.1089/ten.tec.2017.0336

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Citations (28)

Sub-critical impact inhibits cartilage lubrication mechanisms

Osteoarthritis and Cartilage (2015)

Edward D. Bonnevie Michelle L. Delco Lisa A. Fortier Sherry Zhou Devis Galesso

Strain (injury)

White light interferometry

10.1016/j.joca.2015.02.067

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Citations (0)

Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid

PLoS ONE (2015)

Edward D. Bonnevie Devis Galesso Cynthia Secchieri Itai Cohen Lawrence J. Bonassar

When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants.

Boundary lubrication

Synovial joint

10.1371/journal.pone.0143415

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Citations (125)

Degradation alters the lubrication of articular cartilage by high viscosity, hyaluronic acid‐based lubricants

Journal of Orthopaedic Research® (2017)

Edward D. Bonnevie Devis Galesso Cynthia Secchieri Lawrence J. Bonassar

Hyaluronic acid (HA) is widely injected as a viscosupplement in the treatment of osteoarthritis. Despite its extensive use, it is not currently known if cartilage degradation alters how HA-based solutions lubricate the articular surface. In this study we utilized a model of cartilage degradation by IL-1β along with a recently developed framework to study role of cartilage degradation on lubrication by clinically-approved HA-based lubricants with high viscosities. Cartilage explants were cultured up to 8 days with 10 ng/ml IL-1β. After culture, samples were examined histologically, immunohistochemically, biochemically, mechanically, topographically, and tribologically. The tribological testing analyzed both boundary and mixed lubrication modes to assess individual effects of viscosity and boundary lubricating ability. Friction testing was carried out using PBS and two clinically approved HA-based viscosupplements in a cartilage-glass configuration. After culture with IL-1β, boundary mode friction was elevated after both 4 and 8 days. Additionally, friction in mixed mode lubrication, where HA is most effective as a lubricant, was significantly elevated after 8 days of culture. As cartilage became rougher, softer, and more permeable after culture, the boundary mode plateau was extended, and as a result, significantly increased lubricant viscosities or sliding speeds were necessary to achieve effective mixed lubrication. Overall, this study revealed that lubrication of cartilage by HA is degradation-dependent and coincides with changes in mechanics and roughness. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1456-1464, 2018.

Boundary lubrication

Degradation

10.1002/jor.23782

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Citations (28)

Frictional characterization of injectable hyaluronic acids is more predictive of clinical outcomes than traditional rheological or viscoelastic characterization

PLoS ONE (2019)

Edward D. Bonnevie Devis Galesso Cynthia Secchieri Lawrence J. Bonassar

Hyaluronic acid injections have been a mainstay of arthritis treatment for decades. However, much controversy remains about their clinical efficacy and their potential mechanism of action. This approach to arthritis therapy is often called viscosupplementation, a term which is rooted in the elevated viscosity of the injected solutions. This terminology also suggests a mechanical pathway of action and further implies that their efficacy is dependent on viscosity. Notably, previous studies of the relationship between viscous properties of hyaluronic acid solutions and their clinical efficacy have not been definitive. Recently we developed an experimental and analytical framework for studying cartilage lubrication that captures the Stribeck-like behavior of cartilage in an elastoviscous transition curve. Here we apply this framework to study the lubricating behavior of six hyaluronan products currently used for injectable arthritis therapy in the US. Despite the fact that the source and chemical modifications endow these products with a range of lubricating properties, we show that the lubricating effect of all of these materials can be described by this Stribeck-like elastoviscous transition. Fitting this data to the elastoviscous transition model enables the calculation of effective lubricating viscosities for each material, which differ substantially from the viscosities measured using standard rheometry. Further we show that while data from standard rheometry are poor predictors of clinical performance of these materials, measurements of friction coefficient and effective lubricating viscosity correlate well (R2 = 0.77; p < 0.005) with assessments of improved clinical function reported previously. This approach offers both a novel method that can be used to evaluate potential clinical efficacy of hyaluronic acid formulations and provide new insight on their mode of action.

Rheometry

Viscosupplementation

10.1371/journal.pone.0216702

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Citations (39)

Initial investigation of individual and combined annulus fibrosus and nucleus pulposus repair ex vivo

Acta Biomaterialia (2017)

Stephen R. Sloan Devis Galesso Cynthia Secchieri Connor Berlin Roger Härtl

Biomaterial

Intervertebral Disc

Ex vivo

Degeneration (medical)

Degenerative Disc Disease

Annulus (botany)

10.1016/j.actbio.2017.06.045

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Citations (28)

Inflammatory and Noninflammatory Synovial Fluids Exhibit New and Distinct Tribological Endotypes

Journal of Biomechanical Engineering (2020)

Elizabeth Feeney Devis Galesso Cynthia Secchieri Francesca Oliviero Roberta Ramonda

Abstract Inferior synovial lubrication is a hallmark of osteoarthritis (OA), and synovial fluid (SF) lubrication and composition are variable among OA patients. Hyaluronic acid (HA) viscosupplementation is a widely used therapy for improving SF viscoelasticity and lubrication, but it is unclear how the effectiveness of HA viscosupplements varies with arthritic endotype. The objective of this study was to investigate the effects of the HA viscosupplement, Hymovis®, on the lubricating properties of diseased SF from patients with noninflammatory OA and inflammatory arthritis (IA). The composition (cytokine, HA, and lubricin concentrations) of the SF was measured as well as the mechanical properties (rheology, tribology) of the SF alone and in a 1:1 mixture with the HA viscosupplement. Using rotational rheometry, no difference in SF viscosity was detected between disease types, and the addition of HA significantly increased all fluids' viscosities. In noninflammatory OA SF, friction coefficients followed a typical Stribeck pattern, and their magnitude was decreased by the addition of HA. While some of the IA SF also showed typical Stribeck behavior, a subset showed more erratic behavior with highly variable and larger friction coefficients. Interestingly, this aberrant behavior was not eliminated by the addition of HA, and it was associated with low concentrations of lubricin. Aberrant SF exhibited significantly lower effective viscosities compared to noninflammatory OA and IA SF with typical tribological behavior. Collectively, these results suggest that different endotypes of arthritis exist with respect to lubrication, which may impact the effectiveness of HA viscosupplements in reducing friction.

Viscosupplementation

Rheometry

Endotype

10.1115/1.4047628

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Citations (6)

FID-134: a hyaluronan-bisphosphonate macromolecular drug delivery system for intra-articular treatment of osteoarthritis with potential combined cartilage and subchondral bone targeting

Osteoarthritis and Cartilage (2019)

M. Pavan Carlo Barbera Devis Galesso Cynthia Secchieri Stefano Pluda

Viscosupplementation

Bone remodeling

10.1016/j.joca.2019.02.252

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Citations (0)

Identification and characterization of a bacterial hyaluronidase and its production in recombinant form

FEBS Letters (2016)

Luciano Messina J.A. Gavira Salvatore Pernagallo Juan D. Unciti‐Broceta Rosario M. Sánchez‐Martín

Hyaluronidases (Hyals) are broadly used in medical applications to facilitate the dispersion and/or absorption of fluids or medications. This study reports the isolation, cloning, and industrial‐scale recombinant production, purification and full characterization, including X‐ray structure determination at 1.45 Å, of an extracellular Hyal from the nonpathogenic bacterium Streptomyces koganeiensis . The recombinant S. koganeiensis Hyal ( rH yal_Sk) has a novel bacterial catalytic domain with high enzymatic activity, compared with commercially available Hyals, and is more thermostable and presents higher proteolytic resistance, with activity over a broad pH range. Moreover, rH yal_Sk exhibits remarkable substrate specificity for hyaluronic acid (HA) and poses no risk of animal cross‐infection.

Hyaluronidase

Cloning (programming)

Isolation

10.1002/1873-3468.12258

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Citations (20)