The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls. The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa. Immunohistochemistry was performed to evaluate VEGF, monocyte chemotactic protein 1 (MCP-1) and IL-6 proteins. Quantitative real time PCR was performed to evaluate the expression levels of adipocytokines in the OA IFPs. OA IFPs showed an increase in inflammatory infiltration, vascularization and thickness of the interlobular septa compared with controls. VEGF, MCP-1 and IL-6 proteins were higher in OA IFPs compared with in controls. Inflammatory infiltration, hyperplasia, vascularization and fibrosis were increased in OA IFP synovial membranes compared with in those of controls. VEGF protein levels were associated with an increased number of vessels in the OA IFPs, while MCP-1 and IL-6 protein levels were associated with higher grades of inflammatory infiltration. Leptin levels were positively correlated with adiponectin and MCP-1expression, while adiponectin positively correlated with peroxisome proliferative activated receptor gamma, MCP-1 and IFP vascularity. MCP-1 showed a positive correlation with peroxisome proliferative activated receptor gamma. IFP lobules dimensions were positively correlated with IL-6 expression and negatively with thickness of interlobular septa. VEGF mRNA levels were positively correlated with increased synovial vascularity. OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA).

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA.

This paper presents a visco-hyperelastic constitutive model developed to describe the biomechanical response of heel pad tissues. The model takes into account the typical features of the mechanical response such as large displacement, strain phenomena, and non-linear elasticity together with time-dependent effects. The constitutive model was formulated, starting from the analysis of the complex structural and micro-structural configuration of the tissues, to evaluate the relationship between tissue histology and mechanical properties. To define the constitutive model, experimental data from mechanical tests were analyzed. To obtain information about the mechanical response of the tissue so that the constitutive parameters could be established, data from both in vitro and in vivo tests were investigated. Specifically, the first evaluation of the constitutive parameters was performed by a coupled deterministic and stochastic optimization method, accounting for data from in vitro tests. The comparison of constitutive model results and experimental data confirmed the model's capability to describe the compression behaviour of the heel pad tissues, regarding both constant strain rate and stress relaxation tests. Based on the data from additional experimental tests, some of the constitutive parameters were modified in order to interpret the in vivo mechanical response of the heel pad tissues. This approach made it possible to interpret the actual mechanical function of the tissues.

Biomechanical studies are expanding across a variety of fields, from biomedicine to biomedical engineering. From the molecular to the system level, mechanical stimuli are crucial regulators of the development of organs and tissues, their growth and related processes such as remodelling, regeneration or disease. When dealing with cell mechanics, various experimental techniques have been developed to analyse the passive response of cells; however, cell variability and the extraction process, complex experimental procedures and different models and assumptions may affect the resulting mechanical properties. For these purposes, this review was aimed at collecting the available literature focused on experimental chondrocyte and chondron biomechanics with direct connection to their biochemical functions and activities, in order to point out important information regarding the planning of an experimental test or a comparison with the available results. In particular, this review highlighted (i) the most common experimental techniques used, (ii) the results and models adopted by different authors, (iii) a critical perspective on features that could affect the results and finally (iv) the quantification of structural and mechanical changes due to a degenerative pathology such as osteoarthritis.

The infrapatellar fat pad (IFP) can be regarded as a peculiar form of fibro-adipose tissue localized close to the synovial membrane and articular cartilage. The aims of the present study were to analyze the microscopic anatomy of the IFP through histological and ultrastructural methods, comparing it with that of the subcutaneous tissue of the abdomen and of the knee. Ten specimens of IFP were sampled from bodies of the Donation Program of the University of Padua without a history of osteoarthritis. The IFP consisted of white adipose tissue, of lobular type, with lobules delimited by thin connective septa. The IFP lobule areas were smaller (p < 0.05) and the interlobular septa were thicker (p > 0.05) than those of subcutaneous tissues of the abdomen, whereas the IFP lobule areas were larger (p < 0.05) and the interlobular septa were thinner than those of the subcutaneous tissue of the knee (p < 0.05). The IFP adipocytes present a mean area of 3,708 ± 976 µm2 with a large intercellular space, whereas the mean area of the abdominal tissues was greater (6,082 ± 628 µm2; p < 0.05). At scanning electron microscopy the IFP adipocytes were covered by thick fibrillary sheaths, creating a basket around the adipocytes. The structural characteristics of the IFP (lobular aspect of the adipose tissue, thickness of the septa with scarce elastic fibers) could act as a plastic portion aimed at the absorption of pressure variation during knee articular activity. The extensive distribution of nerves suggests a possible role of the IFP as a mechanoreceptor, corresponding to a tridimensional connective mesh working in the proprioceptive regulation of the activity of the knee joint.