Evaluation of cartilage biomechanics and knee joint microenvironment after different cell-based treatments in a sheep model of early osteoarthritis.

PURPOSE: Aiming to prevent cartilage damage during early osteoarthritis (OA), the therapeutic challenge is to restore and maintain the physiological and functional properties of such a tissue with minimally invasive therapeutic strategies. METHODS: Accordingly, an in vivo model of early OA in sheep was here treated through three different cell therapies (culture expanded ADSCs, SVF, and culture expanded AECs) thus to preserve the joint surface from the progression of the pathology. Three months after the treatment injections, their performance was assessed through mechanical automated mapping (Young's modulus and cartilage thickness), gross evaluation of articular surfaces, and biochemical analysis of the synovial fluid. RESULTS: No severe degeneration was observed after three months from OA induction. Cartilage mechanical properties were crucial to identify early degeneration. All the treatments improved the macroscopic cartilage surface aspect and reduced pro-inflammatory cytokines in the synovial fluid. Among the three treatments, SVF highlighted the best performance while ADSCs the worst. CONCLUSION: Despite that the evaluated experimental time is an early follow-up and, thus, longer trial is mandatory to properly assess treatments effectiveness, the proposed multidisciplinary approach allowed to obtain preliminary, but also crucial, results concerning the reduction in OA signs on cartilage properties, in osteophyte development and in all the inflammatory markers.

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

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.

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

Pivoting sports expose athletes to a high risk of knee injuries, mainly due to mechanical overloading of the joint which shatters overall tissue integrity. The present study explored the magnitude of tibiofemoral contact forces (TFCF) in high-risk dynamic tasks. A novel musculoskeletal model with modifiable frontal plane knee alignment was developed to estimate the total, medial, and lateral TFCF developed during vigorous activities. Thirty-one competitive soccer players performing deceleration and 90° sidestepping tasks were assessed via 3D motion analysis by using a marker-based optoelectronic system and TFCF were assessed via OpenSim software. Statistical parametric mapping was used to investigate the effect of frontal plane alignment, compartment laterality, and varus-valgus genu on TFCF. Further, in consideration of specific risk factors, sex influence was also assessed. A strong correlation (R = 0.71 ÷ 0.98, p < 0.001) was found between modification of compartmental forces and changes in frontal plane alignment. Medial and lateral TFCF were similar throughout most of the tasks with the exception of the initial phase, where the lateral compartment had to withstand to higher loadings (1.5 ÷ 3 BW higher, p = 0.010). Significant sex differences emerged in the late phase of the deceleration task. A comprehensive view of factors influencing the mediolateral distribution of TFCF would benefit knee injury prevention and rehabilitation in sport activities.

A Comprehensive Framework to Evaluate the Effects of Anterior Cruciate Ligament Injury and Reconstruction on Graft and Cartilage Status through the Analysis of MRI T2 Relaxation Time and Knee Laxity: A Pilot Study.

BACKGROUND: Anterior cruciate ligament (ACL) tear represents a common orthopedic traumatic issue that often leads to an early development of osteoarthritis. To improve the diagnostic and prognostic techniques involved in the assessment of the joint after the trauma and during the healing process, the present work proposes a multi-parametric approach that aims to investigate the relationship between joint function and soft tissue status before and after ACL reconstruction. METHODS: Thirteen consecutive patients who underwent ACL reconstruction were preliminarily enrolled in this study. Joint laxity assessment as well as magnetic resonance imaging with T2 mapping were performed in the pre-operative stage, at four and 18 months after surgery to acquire objective information to correlate knee function and soft tissue condition. RESULTS: Correlations were found between graft and cartilage T2 signal, suggesting an interplay between these tissues within the knee joint. Moreover, graft maturation resulted in being connected to joint laxity, as underlined by the correlation between the graft T2 signal and the temporal evolution of knee function. CONCLUSIONS: This preliminary study represents a step forward in assessing the effects of ACL graft maturation on knee biomechanics, and vice versa. The presented integrated framework underlines the possibility to quantitatively assess the impact of ACL reconstruction on trauma recovery and cartilage homeostasis. Moreover, the reported findings-despite the preliminary nature of the clinical impacts-evidence the possibility of monitoring the surgery outcomes using a multi-parametric prognostic investigation tool.

Extra-Corporeal Membrane Oxygenation Cadaver Donors: What about Tissues Used as Allografts?

Several studies demonstrated the efficacy of post-mortem extracorporeal membrane oxygenation (ECMO) on donors in preserving organ function addressing organ transplantation. Nevertheless, no common and shared evidence was reached about the possibility of using ECMO donors in tissue harvesting. Therefore, this work aimed first to review the current scientific literature about ECMO donors, and then to focus on the use of ECMO tissues as allografts, mainly addressing musculoskeletal tissues, which are of the most interest for reconstruction. A search was conducted on the current scientific literature, focusing on the keywords "ECMO" and "Donor". Several online databases were used, including PubMed, Scopus, and Web of Science. From the preliminary search, 478 articles were obtained, out of which 173 specifically reported the use of ECMO for donation and transplantation purposes. Literature reported extensive analyses of ECMO organs-overall from the abdomen-both in pre- and post-transplantation studies. On the other hand, ECMO tissues were explanted only in a very limited number of cases; moreover, no information was referred about their status and use. A revision of the current scientific literature highlighted the lack of information concerning ECMO tissues and the necessity to perform preclinical, ex vivo studies to compare allografts from ECMO donors, with respect to standard donors, and, thus, to verify whether they can be harvested and implanted safely and with efficacy.

Anisotropy and inhomogeneity of permeability and fibrous network response in the pars intermedia of the human lateral meniscus.

Within the human tibiofemoral joint, meniscus plays a key role due to its peculiar time-dependent mechanical characteristics, inhomogeneous structure and compositional features. To better understand the pathophysiological mechanisms underlying this essential component, it is mandatory to analyze in depth the relationship between its structure and the function it performs in the joint. Accordingly, the aim of this study was to evaluate the behavior of both solid and fluid phases of human meniscus in response to compressive loads, by integrating mechanical assessment and histological analysis. Cubic specimens were harvested from seven knee lateral menisci, specifically from anterior horn, pars intermedia and posterior horn; unconfined compressive tests were then performed according to three main loading directions (i.e., radial, circumferential and vertical). Fibril modulus, matrix modulus and hydraulic permeability of the tissue were thence estimated through a fibril-network-reinforced biphasic model. Tissue porosity and collagen fibers arrangement were assessed through histology for each region and related to the loading directions adopted during mechanical tests. Regional and strain-dependent constitutive parameters were finally proposed for the human lateral meniscus, suggesting an isotropic behavior of both the horns, and a transversely isotropic response of the pars intermedia. Furthermore, the histological findings supported the evidences highlighted by the compressive tests. Indeed, this study provided novel insights concerning the functional behavior of human menisci by integrating mechanical and histological characterizations and thus highlighting the key role of this component in knee contact mechanics and presenting fundamental information that can be used in the development of tissue-engineered substitutes. STATEMENT OF SIGNIFICANCE: This work presents an integration to the approaches currently used to model the mechanical behavior of the meniscal tissue. This study assessed in detail the regional and directional contributions of both the meniscal solid and fluid phases during compressive response, providing also complementary histological evidence. Within this updated perspective, both knee computational modeling and meniscal tissue engineering can be improved to have an effective impact on the clinical practice.