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Background: Platelets and lymphocytes levels are important in assessing systemic disorders, reflecting inflammatory and immune responses. This study investigated the relationship between blood parameters (platelet count (PLT), mean platelet volume (MPV), lymphocyte count (LINF), and platelet-to-lymphocyte ratio (PLR)) and osteoarthritis (OA) severity, considering age, sex, and body mass index (BMI). Methods: Patients aged ≥40 years were included in this cross-sectional study and divided into groups based on knee OA severity using the Kellgren–Lawrence (KL) grading system. A logistic regression model, adjusted for confounders, evaluated the ability of PLT, MPV, LINF, and PLR to categorize OA severity. Model performance in terms of accuracy, sensitivity, and specificity was assessed using ROC curves. Results: The study involved 245 OA patients (51.4% female, 48.6% male) aged 40–90 years, 35.9% with early OA (KL < 3) and 64.1% moderate/severe OA (KL ≥ 3). Most patients (60.8%) were aged ≥60 years, and BMI was <25 kg/m2 in 33.9%. The model showed that a 25-unit increase in PLR elevates the odds of higher OA levels by 1.30 times (1-unit OR = 1.011, 95% CI [1.004, 1.017], p < 0.005), while being ≥40 years old elevates the odds by 4.42 times (OR 4.42, 95% CI [2.46, 7.95], p < 0.0005). The model's accuracy was 73.1%, with 84% sensitivity, 52% specificity, and an AUC of 0.74 (95% CI [0.675, 0.805]). Conclusions: Higher PLR increases the likelihood of moderate/severe OA, suggesting that monitoring these biomarkers could aid in early detection and management of OA severity. Further research is warranted to cross-validate these results in larger populations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Retrograde Drilling (RD) is a surgical technique employed for osteochondral lesions of the talus (OCLTs) to reach the subchondral bone lesion from behind, thus preserving cartilage integrity. The aim of the present pilot study was to set up an in vitro model of OCLTs to evaluate the regenerative potential of biological approaches that could be associated with the RD technique. Methods: For this purpose, an OCLT was created in human osteochondral specimens, to try to mimic the RD technique, and to compare the regenerative potential of two biological treatments. For this purpose, three groups of treatments were performed in vitro: (1) no treatment (empty defect); (2) autologous bone graft (ABG); (3) hyaluronic membrane enriched with autologous bone marrow cells. Tissue viability; production of Collagen I and II, Vascular Endothelial Growth Factor, and Aggrecan; and histological and microCT evaluations were performed after 30 days of culture in normal culture conditions. Results: It was observed that Group 3 showed the highest viability, and Group 2 showed the highest protein production. From a histological and microtomographic point of view, it was possible to appreciate the structure of the morcellized bone with which the defect of Group 2 was filled, while it was not yet possible to observe the deposition of mineralized tissue in Group 3. Conclusions: To conclude, this pilot study shows the feasibility of an alternative in vitro model to evaluate and compare the regenerative potential of two biological scaffolds, trying to mimic the RD technique as much as possible. The tissues remained vital for up to 4 weeks and both ABG and hyaluronic acid-based scaffolds stimulated the release of proteins linked to regenerative processes in comparison to the empty defect group. [ABSTRACT FROM AUTHOR]

To endow an implant surface with enhanced properties to ensure an appropriate seal with the host tissue for inflammation/infection resistance, next-generation bone implant collagen–polyphenol nanolayers were built on conventional titanium surfaces through a multilayer approach. X-ray Photoelectron Spectroscopy (XPS) analysis was performed to investigate the chemical arrangement of molecules within the surface layer and to provide an estimate of their thickness. A short-term (2 and 4 weeks) in vivo test of bone implants in a healthy rabbit model was performed to check possible side effects of the soft surface layer on early phases of osteointegration, leading to secondary stability. Results show the building up of the different nanolayers on top of titanium, resulting in a final composite collagen–polyphenol surface and a layer thickness of about 10 nm. In vivo tests performed on machined and state-of-the-art microrough titanium implants do not show significant differences between coated and uncoated samples, as the surface microroughness remains the main driver of bone-to-implant contact. These results confirm that the surface nanolayer does not interfere with the onset and progression of implant osteointegration and prompt the green light for specific investigations of the potential merits of this bioactive coating as an enhancer of the device/tissue seal. [ABSTRACT FROM AUTHOR]

This study adopts an in vitro method to recapitulate the behavior of Saos‐2 cells, using a system composed of a perfusion bioreactor and poly‐L‐lactic acid (PLLA) scaffold fabricated using the low‐cost thermally‐induced phase separation (TIPS) technique. Four distinct scaffold morphologies with different pore sizes were fabricated, characterized by Scanning electron microscopy and micro‐CT analysis and tested with osteosarcoma cells under static and dynamic environments to identify the best morphology for cellular growth. In order to accomplish this purpose, cell growth and matrix deposition of the Saos‐2 osteosarcoma cell line were assessed using Picogreen and OsteoImage assays. The obtained data allowed us to identify the morphology that better promotes Saos‐2 cellular activity in static and dynamic conditions. These findings provided valuable insights into scaffold design and fabrication strategies, emphasizing the importance of the dynamic culture to recreate an appropriate 3D osteosarcoma model. Remarkably, the gradient scaffold exhibits promise for osteosarcoma applications, offering the potential for targeted tissue engineering approaches. [ABSTRACT FROM AUTHOR]

In the development of bone graft substitutes, a fundamental step is the use of scaffolds with adequate composition and architecture capable of providing support in regenerative processes both on the tissue scale, where adequate resistance to mechanical stress is required, as well as at the cellular level where compliant chemical–physical and mechanical properties can promote cellular activity. In this study, based on a previous optimization study of this group, the potential of a three-dimensional construct based on polycaprolactone (PCL) and a novel biocompatible Mg- and Sr-containing glass named BGMS10 was explored. Fourier-transform infrared spectroscopy and scanning electron microscopy showed the inclusion of BGMS10 in the scaffold structure. Mesenchymal stem cells cultured on both PCL and PCL-BGMS10 showed similar tendencies in terms of osteogenic differentiation; however, no significant differences were found between the two scaffold types. This circumstance can be explained via X-ray microtomography and atomic force microscopy analyses, which correlated the spatial distribution of the BGMS10 within the bulk with the elastic properties and topography at the cell scale. In conclusion, our study highlights the importance of multidisciplinary approaches to understand the relationship between design parameters, material properties, and cellular response in polymer composites, which is crucial for the development and design of scaffolds for bone regeneration. [ABSTRACT FROM AUTHOR]

The damping system ensured by the osteochondral (OC) unit is essential to deploy the forces generated within load-bearing joints during locomotion, allowing furthermore low-friction sliding motion between bone segments. The OC unit is a multi-layer structure including articular cartilage, as well as subchondral and trabecular bone. The interplay between the OC tissues is essential in maintaining the joint functionality; altered loading patterns can trigger biological processes that could lead to degenerative joint diseases like osteoarthritis. Currently, no effective treatments are available to avoid degeneration beyond tissues' recovery capabilities. A thorough comprehension on the mechanical behaviour of the OC unit is essential to (i) soundly elucidate its overall response to intra-articular loads for developing diagnostic tools capable of detecting non-physiological strain levels, (ii) properly evaluate the efficacy of innovative treatments in restoring physiological strain levels, and (iii) optimize regenerative medicine approaches as potential and less-invasive alternatives to arthroplasty when irreversible damage has occurred. Therefore, the leading aim of this review was to provide an overview of the state-of-the-art—up to 2022—about the mechanical behaviour of the OC unit. A systematic search is performed, according to PRISMA standards, by focusing on studies that experimentally assess the human lower-limb joints' OC tissues. A multi-criteria decision-making method is proposed to quantitatively evaluate eligible studies, in order to highlight only the insights retrieved through sound and robust approaches. This review revealed that studies on human lower limbs are focusing on the knee and articular cartilage, while hip and trabecular bone studies are declining, and the ankle and subchondral bone are poorly investigated. Compression and indentation are the most common experimental techniques studying the mechanical behaviour of the OC tissues, with indentation also being able to provide information at the micro- and nanoscales. While a certain comparability among studies was highlighted, none of the identified testing protocols are currently recognised as standard for any of the OC tissues. The fibril-network-reinforced poro-viscoelastic constitutive model has become common for describing the response of the articular cartilage, while the models describing the mechanical behaviour of mineralised tissues are usually simpler (i.e., linear elastic, elasto-plastic). Most advanced studies have tested and modelled multiple tissues of the same OC unit but have done so individually rather than through integrated approaches. Therefore, efforts should be made in simultaneously evaluating the comprehensive response of the OC unit to intra-articular loads and the interplay between the OC tissues. In this regard, a multidisciplinary approach combining complementary techniques, e.g., full-field imaging, mechanical testing, and computational approaches, should be implemented and validated. Furthermore, the next challenge entails transferring this assessment to a non-invasive approach, allowing its application in vivo, in order to increase its diagnostic and prognostic potential. [ABSTRACT FROM AUTHOR]

There is increasing interest in using magnesium (Mg) alloy orthopedic devices because of their mechanical properties and bioresorption potential. Concerns related to their rapid degradation have been issued by developing biodegradable micro- and nanostructured coatings to enhance corrosion resistance and limit the release of hydrogen during degradation. This systematic review based on four databases (PubMed®, Embase, Web of Science™ and ScienceDirect®) aims to present state-of-the-art strategies, approaches and materials used to address the critical factors currently impeding the utilization of Mg alloy devices. Forty studies were selected according to PRISMA guidelines and specific PECO criteria. Risk of bias assessment was conducted using OHAT and SYRCLE tools for in vitro and in vivo studies, respectively. Despite limitations associated with identified bias, the review provides a comprehensive analysis of preclinical in vitro and in vivo studies focused on manufacturing and application of Mg alloys in orthopedics. This attests to the continuous evolution of research related to Mg alloy modifications (e.g., AZ91, LAE442 and WE43) and micro- and nanocoatings (e.g., MAO and MgF2), which are developed to improve the degradation rate required for long-term mechanical resistance to loading and excellent osseointegration with bone tissue, thereby promoting functional bone regeneration. Further research is required to deeply verify the safety and efficacy of Mg alloys. [ABSTRACT FROM AUTHOR]

Adolescent Idiopathic Scoliosis (AIS) is the most common form of three-dimensional spinal disorder in adolescents between the ages of 10 and 18 years of age, most commonly diagnosed in young women when severe disease occurs. Patients with AIS are characterized by abnormal skeletal growth and reduced bone mineral density. The etiology of AIS is thought to be multifactorial, involving both environmental and genetic factors, but to date, it is still unknown. Therefore, it is crucial to further investigate the molecular pathogenesis of AIS and to identify biomarkers useful for predicting curve progression. In this perspective, the relative abundance of a panel of microRNAs (miRNAs) was analyzed in the plasma of 20 AIS patients and 10 healthy controls (HC). The data revealed a significant group of circulating miRNAs dysregulated in AIS patients compared to HC. Further bioinformatic analyses evidenced a more restricted expression of some miRNAs exclusively in severe AIS females. These include some members of the miR-30 family, which are considered promising regulators for treating bone diseases. We demonstrated circulating extracellular vesicles (EVs) from severe AIS females contained miR-30 family members and decreased the osteogenic differentiation of mesenchymal stem cells. Proteomic analysis of EVs highlighted the expression of proteins associated with orthopedic disease. This study provides preliminary evidence of a miRNAs signature potentially associated with severe female AIS and suggests the corresponding vesicular component may affect cellular mechanisms crucial in AIS, opening the scenario for in-depth studies on prognostic differences related to gender and grade. [ABSTRACT FROM AUTHOR]

The objective of this review is to systematically analyze the potential correlation between gut microbiota and osteoarthritis (OA) as well as to evaluate the feasibility of microbiota-targeted therapies for treating OA. Studies conducted from October 2013 to October 2023 were identified via a search on electronic databases such as PubMed, Web of Science, and Scopus, following established PRISMA statement standards. Two reviewers independently screened, assessed, and extracted relevant data, and then they graded the studies using the ROBINS I tool for non-randomized interventions studies and SYRCLE's risk-of-bias tool for animal studies. A search through 370 studies yielded 38 studies (24 preclinical and 14 clinical) that were included. In vivo research has predominantly concentrated on modifying the gut microbiota microenvironment, using dietary supplements, probiotics, and prebiotics to modify the OA status. Lactobacilli are the most thoroughly examined with Lactobacillus acidophilus found to effectively reduce cartilage damage, inflammatory factors, and pain. Additionally, Lactobacillus M5 inhibits the development of OA by preventing high-fat diet (HFD)-induced obesity and protecting cartilage from damage. Although there are limited clinical studies, certain compositions of intestinal microbiota may be associated with onset and progression of OA, while others are linked to pain reduction in OA patients. Based on preclinical studies, there is evidence to suggest that the gut microbiota could play a significant role in the development and progression of OA. However, due to the scarcity of clinical studies, the exact mechanism linking the gut microbiota and OA remains unclear. Further research is necessary to evaluate specific gut microbiota compositions, potential pathogens, and their corresponding signaling pathways that contribute to the onset and progression of OA. This will help to validate the potential of targeting gut microbiota for treating OA patients. [ABSTRACT FROM AUTHOR]

The use of minimally manipulated adipose tissue (MM-AT) products is gaining increasing interest for the treatment of knee osteoarthritis (OA). MM-AT represents an easy way to exploit adipose tissue properties, although clinical evidence is still limited, as well as their benefits with respect to more documented orthobiologics like platelet-rich plasma (PRP). A systematic review and meta-analysis were performed to evaluate the safety and efficacy of MM-AT products for knee OA management. The risk of bias of the included studies was evaluated using the Dawns and Black checklist for all the included studies and RoB-2.0 for randomized controlled trials (RCTs). Thirty-three clinical studies were included in the qualitative analysis: 13 prospective case series, 10 retrospective case series, 7 RCTs, 2 retrospective comparative studies, and 1 prospective comparative study. An overall clinical improvement and few minor adverse events were observed. Five RCTs comparing MM-AT and PRP injections were meta-analyzed, showing comparable results. The analysis also highlighted the limits of the literature, with only a few high-level trials and an overall low quality. Even though the current literature is still limited, the available evidence suggests the safety and overall positive results of the intra-articular injections of MM-AT products for knee OA treatment. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease that is age-related and progressive. It causes the destruction of articular cartilage and underlying bone, often aggravated by inflammatory processes and oxidative stresses. This pathology impairs the quality of life of the elderly, causing pain, reduced mobility, and functional disabilities, especially in obese patients. Phytochemicals with anti-inflammatory and antioxidant activities may be used for long-term treatment of OA, either in combination with current anti-inflammatories and painkillers, or as an alternative to other products such as glucosamine and chondroitin, which improve cartilage structure and elasticity. The current systematic review provides a comprehensive understanding of the use of flavonoids. It highlights chondrocyte, cartilage, and subchondral bone activities, with a particular focus on their nutrigenomic effects. The molecular mechanisms of these molecules demonstrate how they can be used for the prevention and treatment of OA in the elderly population. However, clinical trials are still needed for effective use in clinical practice. [ABSTRACT FROM AUTHOR]

Poly-ε-caprolactone (PCL) has been widely used in additive manufacturing for the construction of scaffolds for bone tissue engineering. However, its use is limited by its lack of bioactivity and inability to induce cell adhesion, hence limiting bone tissue regeneration. Biomimicry is strongly influenced by the dynamics of cell–substrate interaction. Thus, characterizing scaffolds at the cell scale could help to better understand the relationship between surface mechanics and biological response. We conducted atomic force microscopy-based nanoindentation on 3D-printed PCL fibers of ~300 µm thickness and mapped the near-surface Young's modulus at loading forces below 50 nN. In this non-disruptive regime, force mapping did not show clear patterns in the spatial distribution of moduli or a relationship with the topographic asperities within a given region. Remarkably, we found that the average modulus increased linearly with the logarithm of the strain rate. Finally, a dependence of the moduli on the history of nanoindentation was demonstrated on locations of repeated nanoindentations, likely due to creep phenomena capable of hindering viscoelasticity. Our findings can contribute to the rational design of scaffolds for bone regeneration that are capable of inducing cell adhesion and proliferation. The methodologies described are potentially applicable to various tissue-engineered biopolymers. [ABSTRACT FROM AUTHOR]