Osteoarthritic synovial fluid rheology and correlations with protein concentration

Madkhali, Anwar; Chernos, Michael; Grecov, Dana; Kwok, Ezra

doi:10.3233/bir-15078

Cited by 17 publications

(10 citation statements)

References 81 publications

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“…With disease progression a reduction in the synovial fluid viscosity is observed. 68 Current treatment in early onset OA can involve viscosupplements like hyaluronic acid. As these increase the viscosity of the synovial fluid, they will increase the retention of the drug in the joint.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage: Effect of Synovial Clearance and Compressive Load

Spitters

Stamatialis

Petit³

et al. 2019

ASSAY and Drug Development Technologies

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Intra-articular injection of drug depots is considered as a therapeutic strategy for the treatment of osteoarthritis. In this study, we designed an in vitro assay in a previously described bioreactor system to evaluate the uptake of a small molecule drug mimic as a function of drug clearance by the synovium and compressive load. Bromophenol blue (BPB) loaded hydrogels were placed on top of bovine articular cartilage explants and were compressed in a dual flow bioreactor. As a control, BPB was directly injected in the bioreactor compartment mimicking the synovial fluid. Subsequently, diffusion coefficients of the dye were estimated based on Fick's law. Mimicking synovial clearance revealed that dye penetration of BPB when released from a drug delivery system placed on top of a cartilage explant was enhanced compared to direct injection of BPB into a simulated synovial fluid. Furthermore, we show the synergistic effect of the amount of load and the frequency on drug uptake by the cartilage. In the described model, we have shown that, under compressive load, drug delivery from a depot was beneficial over conventional intra-articular drug administration. The assay mimics the complexity of the knee joint in several key aspects, which results in a more close representation of the expected drug outcome. In this study, we have evaluated the penetration of a model small molecule drug into articular cartilage under compressive conditions, and future development will focus on incorporating synovial(-like) fluid, synovium, and bone to increase the predictive potential of the assay further.

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Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage: Effect of Synovial Clearance and Compressive Load

Spitters

Stamatialis

Petit³

et al. 2019

ASSAY and Drug Development Technologies

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“…With the zero-shear viscosity

, the infinite shear viscosity

, the Cross time constant C and the Cross rate constant m . The four Cross constants were fitted following the rheological models suggested in literature for bovine serum [ 33 ] and human synovial fluid [ 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

“…For human synovial fluid, a non-Newtonian shear thinning behavior is usually observed [24][25][26]. Common rheological models to simulate this kind of nonlinearity are the Cross and Carreau models, which are also able to model zero-shear viscosity and infinite shear viscosity [27,28].…”

Section: Introductionmentioning

confidence: 99%

Rheologic Behavior of Bovine Calf Serum

et al. 2021

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Recent studies have illuminated the rheological behavior of synovial fluid and the role of protein and hyaluronan (HA). However, with respect to artificial joint replacement in standardized wear simulations, bovine serum is used as fluid test medium. Little is known about the rheological characteristics of bovine serum, which are needed for precise tribological investigations. The steady shear viscosity η of bovine calf serum is determined for protein concentrations used in standardized wear simulations depending on shear rate γ˙ and temperature T. Additionally, the density of the serum is determined for both protein concentrations. The results show shear thinning behavior of bovine calf serum with a nearly Newtonian behavior in the range of high shear rates. Within the range of high shear rates, mean viscosities of η = 0.82–0.88 mPa·s were found for protein concentrations of 20 g/L and mean viscosities of η = 0.88–0.94 mPa·s for 30 g/L, decreasing with temperature. Densities of 1.004–1.005 g/cm3 and 1.007–1.008 g/cm3 were found for 20 and 30 g/L protein concentrations, respectively.

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“…Its function is to nourish cartilage and lubricate joints for which lubricin, a glycocomposite binded to hyaluronan (HA), plays a major role [44][45][46]. During OA, synovial fluid proteins become progressively denatured [47]. Plasma infiltration induces a decrease in HA concentration and molecular weight, caused by abnormal metabolic processes [48].…”

Section: Synoviummentioning

confidence: 99%

Molecular analysis of the destruction of articular joint tissues by Raman spectroscopy

Casal-Beiroa

González

Blanco

et al. 2020

Expert Review of Molecular Diagnostics

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Introduction: Osteoarthritis (OA) is a highly heterogenous disease influenced by different molecular, anatomic and physiologic imbalances. Some of the bottlenecks for enhanced diagnosis and therapeutic assessment are the lack of validated biomarkers and early diagnosis tools. In this narrative review, we analyze the potential of Raman spectroscopy (RS) as a label-free optical tool for the characterization of articular joint tissues and its application as a diagnosis tool for OA.Areas covered: Raman spectra produce a unique "molecular fingerprint" providing rotational and vibrational molecular information, allowing the identification and follow-up of molecular changes associated with OA pathological mechanisms. Focusing on multiple joint tissues (cartilage, synovium, bone, tendons, ligaments and meniscus) and their contribution in disease incidence and progression, this review highlights the current knowledge on the application of RS in the characterization of organic and inorganic molecules present at these tissues and alterations that occur in the onset of OA.Expert Opinion: Vibrational spectroscopy techniques, such as RS, are low cost, rapid and minimally invasive approaches that offer high specificity in the assessment of the molecular composition of complex tissues. Combined with multivariate statistical methods, RS offers great potential for optical biomarkers discovery or disease diagnosis applications, and we hereby discuss clinical translational progresses on the field.

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Osteoarthritic synovial fluid rheology and correlations with protein concentration

Abstract: Increased protein concentration has been correlated with decreased shear rheological parameters. Temperature dependence of synovial fluid was also demonstrated and modelled for use in Part 2 of this article.

Cited by 17 publications

References 81 publications

In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage: Effect of Synovial Clearance and Compressive Load

In Vitro Evaluation of Small Molecule Delivery into Articular Cartilage: Effect of Synovial Clearance and Compressive Load

Rheologic Behavior of Bovine Calf Serum

Molecular analysis of the destruction of articular joint tissues by Raman spectroscopy

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