Meniscal biomechanical alterations in an ACLT rabbit model of early osteoarthritis.

OBJECTIVE: The purpose of this study was to analyze the early biomechanical alterations of menisci during the early stage of osteoarthritis (OA) development and to correlate them with the chemical composition and matrix alteration. A particular focus was paid to pathological changes in glycosaminoglycan (GAG) content and collagen fiber architecture. DESIGN: Menisci (n = 24) were removed from rabbits' knee joints 6 weeks following surgical anterior cruciate ligament transection (ACLT). Both the anterior and posterior regions of medial and lateral menisci were characterized using indentation tests, Raman microspectroscopy (RM), biphotonic confocal microscopy (BCM) and histology. RESULTS: Mechanical and matrix alterations occurred in both regions of medial and lateral menisci. A significant decrease in the mechanical properties was observed in OA menisci, with a mean reduced modulus from 2.3 to 1.1 MPa. Microstructural observations revealed less organized and less compact collagen bundles in operated menisci than in contralateral menisci, as well as a loss of fiber tension. GAG content was increased in OA menisci, especially in the damaged areas. Neither changes in the secondary structure of collagen nor mineralization were detected through RM at this stage of OA. CONCLUSION: ACLT led to a disorganization of the collagen framework at the early stage of OA development, which decreases the mechanical resistance of the menisci. GAG content increases in response to this degradation. All of these results demonstrate the strong correlation between matrix and mechanical alterations.

Development of a mechanical characterisation device for intracranial aneurysms: Calibration on polymeric phantom arteries.

Intracranial aneurysm is a major health issue related to biomechanical arterial wall degradation. Currently, no method allows predicting rupture risk based on in vivo quantitative mechanical data. This work is part of a large-scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool, based on the in vivo mechanical characterisation of the aneurysm wall. Thus, the primary objective of the project was to develop a deformation device prototype (DDP) of the artery wall and to calibrate it on polymeric phantom arteries. The deformations induced on the phantom arteries were quantified experimentally using a Digital Image Correlation (DIC) system. The results indicated that the DIC system was able to measure the small displacements generated by the DDP. We also observed that the flow mimicking the blood flow did not significantly disturb the measurements of the artery wall displacement caused by the DDP. Finally, a limit displacement value generated by the DDP was evaluated. This value corresponds to the lowest displacement value detectable by the clinical imaging system that will be tested on animals in the future (Spectral Photon Counting CT).

In vivo mechanical characterization of arterial wall using an inverse analysis procedure: application on an animal model of intracranial aneurysm.

Intracranial aneurysm is a pathology related to the deterioration of the arterial wall. This work is an essential part of a large-scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool to facilitate the rupture risk assessment. It will lean on the link between the aneurysm shape clinically observed and a database derived from the in vivo mechanical characterization of aneurysms. To supply this database, a deformation device prototype of the arterial wall was developed. Its use coupled with medical imaging (spectral photon-counting computed tomography providing a spatial resolution down to 250 µm) is used to determine the in vivo mechanical properties of the wall based on the inverse analysis of the quantification of the wall deformation observed experimentally. This study presents the in vivo application of this original procedure to an animal model of aneurysm. The mechanical properties of the aneurysm wall identified were consistent with the literature, and the errors between the numerical and experimental results were less than 10%. Based on these parameters, this study allows the assessment of the aneurysm stress state for a known solicitation and points towards the definition of a rupture criterion.

Towards the mechanical characterisation of unruptured intracranial aneurysms: Numerical modelling of interactions between a deformation device and the aneurysm wall.

Intracranial aneurysm is a critical pathology related to the arterial wall deterioration. This work is an essential aspect of a large scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool regarding the rupture risk assessment. A machine learning algorithm links the aneurysm shape observed and a database of UIA clinical images associated with in vivo wall mechanical properties and rupture characterisation. The database constitution is derived from a device prototype coupled with medical imaging. It provides the mechanical characterisation of the aneurysm from the wall deformation obtained by inverse analysis based on the variation of luminal volume. Before performing in vivo tests of the device on small animals, a numerical model was built to quantify the device's impact on the aneurysm wall under natural blood flow conditions. As the clinician will never be able to precisely situate the device, several locations were considered. In preparation for the inverse analysis procedure, artery material laws of increasing complexity were studied (linear elastic, hyper elastic Fung-like). Considering all the device locations and material laws, the device induced relative displacements to the Systole peak (worst case scenario with the highest mechanical stimulus linked to the blood flow) ranging from 375 µm to 1.28 mm. The variation of luminal volume associated with the displacements was between 0.95 % and 4.3 % compared to the initial Systole volume of the aneurysm. Significant increase of the relative displacements and volume variations were found with the study of different cardiac cycle moments between the blood flow alone and the device application. For forthcoming animal model studies, Spectral Photon CT Counting, with a minimum spatial resolution of 250 µm, was selected as the clinical imaging technique. Based on this preliminary study, the displacements and associated volume variations (baseline for inverse analyse), should be observable and exploitable.

Effects of a viscosupplementation therapy on rabbit menisci in an anterior cruciate ligament transection model of osteoarthritis.

The aim of this study was to evaluate the morphological, microstructural, and mechanical effects of a viscosupplementation therapy on rabbit menisci at an early stage of osteoarthritis (OA). Anterior cruciate ligament transection (ACLT) was performed in twelve male New-Zealand White rabbits on the right knee joint. Six of these twelve rabbits received a mono intra-articular injection of high molecular weight hyaluronic acid (HA) two weeks after ACLT. Six additional healthy rabbits served as controls. Medial menisci were removed from all right knees (n=18) six weeks after ACLT and were graded macroscopically. Indentation-relaxation tests were performed in the anterior and posterior regions of the menisci. Collagen fiber organization and glycosaminoglycan (GAG) content were assessed by biphotonic confocal microscopy and histology, respectively. Viscosupplementation significantly (p=0.002) improved the surface integrity of the medial menisci compared to the operated non-treated group. Moreover, the injection seems to have an effect on the GAG distribution in the anterior region of the menisci. However, the viscoelastic properties of both operated groups were similar and significantly lower than those of the healthy group, which was explained by their modified collagen fiber organization. They displayed disruption of the tie fibers due to structural alterations of the superficial layers from which they emanate, leading to modifications in the deep zone. To conclude, the viscosupplementation therapy prevents macroscopic lesions of the menisci, but it fails to restore their collagen fiber organization and their viscoelastic properties. This finding supports the role of this treatment in improving the lubrication over the knee.

Viscoelastic properties of rabbit osteoarthritic menisci: A correlation with matrix alterations.

The aim of this study was to evaluate the effect of early osteoarthritis (OA) on the viscoelastic properties of rabbit menisci and to correlate the mechanical alterations with the microstructural changes. Anterior Cruciate Ligament Transection (ACLT) was performed in six male New-Zealand White rabbits on the right knee joint. Six healthy rabbits served as controls. Menisci were removed six weeks after ACLT and were graded macroscopically. Indentation-relaxation tests were performed in the anterior and posterior regions of the medial menisci. The collagen fibre organization and glycosaminoglycan (GAG) content were assessed by biphotonic confocal microscopy and histology, respectively. OA menisci displayed severe macroscopic lesions compared with healthy menisci (p=0.009). Moreover, the instantaneous and equilibrium moduli, which were 2.9±1.0MPa and 0.60±0.18MPa in the anterior region of healthy menisci, respectively, decreased significantly (p=0.03 and p=0.004, respectively) in OA menisci by 55% and 57%, respectively, indicating a global decrease in meniscal stiffness in this region. The equilibrium modulus alone decreased significantly (p=0.04) in the posterior region, going from 0.60±0.18MPa to 0.26±012MPa. This induced a loss of tissue elasticity. These mechanical changes were associated in the posterior region with a structural disruption of the superficial layers, from which the tie fibres emanate, and with a decrease in the GAG content in the anterior region. Consequently, the circumferential collagen fibres of the deep zone were dissociated and the collagen bundles were less compact. Our results demonstrate the strong meniscal modifications induced by ACLT at an early stage of OA and highlight the relationship between structural and chemical matrix alterations and mechanical properties.