Search Results (25)

Osteoporosis (OP) and osteoarthritis (OA) are two common degenerative musculoskeletal disorders associated with aging and are traditionally classified and managed as distinct disease entities. Emerging evidence suggests that OP and OA may share bidirectional associations and common biological mechanisms, and that under specific pathological conditions they may develop into a mutually reinforcing comorbid state. The comorbidity of osteoporosis and osteoarthritis (OP–OA) is not a simple superimposition of bone loss and cartilage degeneration; rather, it represents a disorder of the osteochondral unit centered on disruption of the subchondral bone microenvironment. Alterations in the structural strength, remodeling dynamics, vascular and neural status, and bone marrow lesions of subchondral bone collectively reshape the local microenvironment, thereby directly affecting mechanical signal transmission and cellular behavior within the joint. Focusing on the subchondral bone microenvironment as the central pathological nexus, this review systematically summarizes how mechanical imbalance, aberrant bone remodeling, inflammatory activation, metabolic dysregulation, and cellular senescence jointly remodel the local niche in OP–OA comorbidity. These microenvironmental changes further induce phenotypic remodeling and fate deviation of bone marrow mesenchymal stem cells, bone remodeling-related cells, osteoimmune cells, and chondrocytes. On this basis, we integrate the regulatory roles of developmental signaling, mechanotransduction pathways, and inflammatory–immune signaling networks, and propose that microenvironment-driven cell fate plasticity may serve as a key mechanistic hub promoting the initiation and progression of OP–OA comorbidity as well as the persistent destabilization of the osteochondral unit. This perspective may help overcome the limitations of current studies that address OP and OA separately, and may provide a theoretical framework for early identification and stratification, biomarker discovery, and combined precision-targeted interventions for this comorbid condition. Full article

Osteochondral defects of the knee represent a significant clinical challenge due to the limited regenerative capacity of the osteochondral unit. The aim of this study was to evaluate the therapeutic potential of calcium phosphate-based biomaterials combined with honey in a porcine model. Osteochondral defects were surgically induced and treated with a custom-prepared composite material. Tissue regeneration was assessed using integrated macroscopic and microscopic evaluation, supported by multimodal imaging techniques. The outcomes were compared with both a spontaneous healing group and a control site with native cartilage. The composite biomaterial significantly enhanced osteochondral regeneration, with results comparable to healthy cartilage. Notably, improved structural organization and more advanced healing responses were observed in the treated group compared to spontaneous healing. The beneficial effects are attributed to the anti-inflammatory, antimicrobial, antioxidant, and immunomodulatory properties of honey, which may enhance the regenerative microenvironment and support tissue repair. These findings highlight the potential of calcium phosphate-based biomaterials combined with honey as a promising strategy for osteochondral defect treatment, improving structural, biological, and biomechanical aspects of healing. Full article

Damage to the osteochondral unit is a common cause of lameness in horses. Published descriptions of MRI findings of osteochondral unit and subchondral damage are currently lacking, and only a few reports describe outcomes in sport horses. The aims of this case series retrospective study were to describe different MRI patterns of osteochondral/subchondral pathology in the fetlock joint using low-field MRI and to provide outcome information. A total of 35 sport horses were included. Data regarding detailed clinical history, treatment and outcome were evaluated. MRI identified a total of 39 bone lesions: 14 were limited to the subchondral plate, and 25 involved the whole osteochondral unit. In 12 horses, a fissure was observed. Areas of high signal intensity on STIR sequences and low signal intensity on T1-weighted sequences within the trabecular bone were observed in association with subchondral and osteochondral unit damage. At follow-up, a persistent lameness was observed in 11 horses, all of which presented with a lesion involving the whole osteochondral unit. Different MRI patterns consistent with lesions involving either the entire osteochondral unit or only the subchondral bone plate could be identified using low-field MRI. MRI examination should be recommended in horses with inconclusive radiographic findings. Our results suggest that lesions limited to the subchondral bone are associated with a better prognosis. Full article

Background: A trilayered collagen/collagen–magnesium–hydroxyapatite (Col/Col-Mg-HA) scaffold is used in clinical practice to treat osteochondral lesions, but the regeneration of the subchondral bone is still not satisfactory. Objective: The aim of this study was to test, in vitro, the osteoinductivity induced by the addition of bone morphogenetic protein-2 (BMP-2) or amorphous calcium phosphate granules with strontium ions (Sr-ACP), in order to improve the clinical regeneration of subchondral bone, still incomplete. Methodology: Normal human osteoblasts (NHOsts) were seeded on the scaffolds and grown for 14 days in the presence of human osteoclasts and conditioned medium of human endothelial cells. NHOst adhesion and morphology were observed with transmission electron microscopy, and metabolic activity was tested by Alamar blue assay. The expression of osteoblast- and osteoclast-typical markers was evaluated by RT-PCR on scaffolds modified by enrichment with BPM-2 or Sr-ACP, as well as on unmodified material used as a control. Results: NHOsts adhered well to all types of scaffolds, maintained their typical morphology, and secreted abundant extracellular matrix. On the modified materials, COL1A1, SPARC, SPP1, and BGLAP were more expressed than on the unmodified ones, showing the highest expression in the presence of BMP-2. On Sr-ACP-enriched scaffolds, NHOsts had a lower proliferation rate and a lower expression of RUNX2, SP7, and ALPL compared to the other materials. The modified scaffolds, particularly the one containing Sr-ACP, increased the expression of the osteoclasts’ typical markers and decreased the OPG/RANKL ratio. Both types of scaffold modification were able to increase the osteoinductivity with respect to the original scaffold used in clinical practice. BMP-2 modification seemed to be more slightly oriented to sustain NHOst activity, and Sr-ACP seemed to be more slightly oriented to sustain the osteoclast activity. These could provide a concerted action toward better regeneration of the entire osteochondral unit. Full article

Osteochondral regeneration remains a major clinical challenge due to the complex architecture and biomechanical demands of the osteochondral unit. Bioactive hydrogels have emerged as promising materials capable of supporting repair through their capacity to mimic the extracellular matrix (ECM), enable cell encapsulation, and deliver bioactive cues. However, recent insights reveal that simply engineering hydrogels for structural and cellular support is insufficient. A new paradigm is emerging—one that embraces the complexity of the osteochondral niche by integrating immunomodulatory and mechanobiological cues into biomaterial design. In particular, the hydrogel’s capacity to modulate macrophage polarization and support the immunoregulatory function of mesenchymal stem cells (MSCs) is critical to orchestrate regenerative outcomes. Simultaneously, the mechanical properties of hydrogels—such as stiffness, porosity, and viscoelasticity—can profoundly influence stem cell fate and local tissue morphogenesis. This review discusses recent advances in hydrogel-based strategies for osteochondral repair, highlighting the interplay between immunological signals and the mechanical microenvironment, and calls for a shift from reductionist tissue-engineering approaches to systems-level design of tunable, immuno-mechanobiological microenvironments. Full article

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health. Full article

Osteochondral defects, involving both articular cartilage and subchondral bone, pose significant challenges to joint function and health due to the lack of spontaneous healing and the risk of long-term degenerative diseases like osteoarthritis. Biomaterials have emerged as important components in the development of scaffolds, providing structural support that facilitates tissue growth, integration, and regeneration. This study aims to demonstrate the effectiveness of a tomographic assessment method for optimizing the evaluation of osteochondral regeneration, particularly using Hounsfield units, to enable the evaluation of scaffold integration and tissue regeneration. The sheep model was selected as a model study. Two distinct configurations of biomaterials were utilized in this study: Honey (HMG—Mg doped hydroxyapatite; HWS—wollastonite–hydroxyapatite) and Bi-layer (BWS—wollastonite–hydroxyapatite). The HMG scaffold demonstrated superior integration, reparative tissue quality, and regeneration potential compared to the HWS, BWS, and CTRL groups. The findings underscore the significance of CT assessment as a preliminary method for evaluating hard tissue, such as bone, employing Hounsfield units. Statistical evaluations validated the significant differences in performance, particularly favoring the HMG group. The results of this study underscore the importance of tomographic assessment in evaluation of osteochondral regeneration. Full article

This pilot study examined the long-term structural changes in the osteochondral unit of 20 patients with knee osteoarthritis (KOA) who underwent high tibial osteotomy (HTO) and received post-treatment with either platelet-rich plasma (PRP) or stromal vascular fraction (SVF). Ten patients were injected with autologous PRP (PRP subgroup), while another ten patients received autologous SVF (SVF subgroup) six weeks after surgery and were monitored for 18 months. Histological samples of bone and cartilage (2 mm in diameter and 2 cm long) were taken from tibial and femoral sites during surgery and 18-month post-HTO, and morphometric analyses were conducted using Mega-Morf12 software. Both post-treatment resulted in an increase in articular cartilage height at both sites (p < 0.001 in the tibia and femur), indicating positive outcomes. Significant improvements in subchondral and trabecular bone architecture were also observed, with SVF injection showing higher reparative capacity in terms of bone volume (p < 0.001 for the tibia and p = 0.004 for the femur), subchondral bone height (p < 0.001 for the tibia and p = 0.014 for the femur), trabecular bone volume (p < 0.001 for the femur), and intertrabecular space (p = 0.009 for the tibia and p = 0.007 for the femur). This pilot study, for the first time, demonstrates that HTO surgery combined with PRP and SVF post-treatments can lead to significant enhancements in knee articular cartilage and bone architecture in KOA patients, with SVF showing higher regenerative potential. These findings may contribute to improving treatment strategies for better clinical outcomes in HTO therapy for patients with KOA. Full article

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. Full article

The unique physical demands of tactical athletes put immense stress on the knee joint, making these individuals susceptible to injury. In order to ensure operational readiness, management options must restore and preserve the native architecture and minimize downtime, while optimizing functionality. Osteochondral lesions (OCL) of the knee have long been acknowledged as significant sources of knee pain and functional deficits. The management of OCL is predicated on certain injury characteristics, including lesion location and the extent of subchondral disease. Techniques such as marrow stimulation, allograft and autologous chondrocyte implantation are examined in detail, with a focus on their application and suitability in tactical athlete populations. Moreover, the restoration of the osteochondral unit (OCU) is highlighted as a central aspect of knee joint preservation. The discussion encompasses the biomechanical considerations and outcomes associated with various cartilage restoration techniques. Factors influencing procedure selection, including lesion size, location, and patient-specific variables, are thoroughly examined. Additionally, the review underscores the critical role of post-operative rehabilitation and conditioning programs in optimizing outcomes. Strengthening the surrounding musculature, enhancing joint stability, and refining movement patterns are paramount in facilitating the successful integration of preservation procedures. This narrative review aims to provide a comprehensive resource for surgeons, engineers, and sports medicine practitioners engaged in the care of tactical athletes and the field of cartilage restoration. The integration of advanced preservation techniques and tailored rehabilitation protocols offers a promising avenue for sustaining knee joint health and function in this demanding population. Full article

Among available papers published on the given subject over the last century, various terms have been used as synonyms for one, now generally accepted—osteoarthritis, in some countries called “wear and tear” or “overload arthritis”. The opsolent terms—hypertrophic arthritis, degenerative arthritis, arthritis deformans and osteoarthrosis—sought to highlight the dominant clinical signs of this ubiquitous, polymorph disease of the whole osteochondral unit, which by incidence and prevalence represents one of the leading chronic conditions that cause long-term pain and incapacity for work. Numerous in vitro and in vivo research resulted in broadened acknowledgments about osteoarthritis pathophysiology and pathology on both histological and cellular levels. However, the cause of osteoarthritis is still unknown and is currently the subject of a hypothesis. In this paper, we provide a review of recent findings on biological phenomena taking place in bone tissue during osteoarthritis to the extent useful for clinical practice. Choosing a proper radiological approach is a conditio sine qua non to the early diagnosis of this entity. Full article

Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These “foreign bodies” serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments—the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints. Full article

With the increase in population aging, the tendency of osteochondral injury will be accelerated, and repairing materials are increasingly needed for the optimization of the regenerative processes in bone and cartilage recovery. The local environment of the injury sites and the deficiency of Mg²⁺ retards the repairing period via inhibiting the progenitor osteogenesis and chondrogenesis cells’ recruitment, proliferation, and differentiation, which results in the sluggish progress in the osteochondral repairing materials design. In this article, we elucidate the Mg²⁺-concentration specified effect on the cell proliferation, osteochondral gene expression, and differentiation of modeling chondrocytes (extracted from New Zealand white rabbit) and osteoblasts (MC3T3-E1). The concentration of Mg²⁺ in the culture medium affects the proliferation, chondrogenesis, and osteogenesis: (i) Appropriate concentrations of Mg²⁺ promote the proliferation of chondrocytes (1.25–10.0 mM) and MC3T3-E1 cells (2.5–30.0 mM); (ii) the optimal concentration of Mg²⁺ that promotes the gene expression of noncalcified cartilage is 15 mM, calcified cartilage 10 mM, and subchondral bone 5 mM, respectively; (iii) overdosed Mg²⁺ leads to the inhibition of cell activity for either chondrocytes (>20 mM) or osteoblasts (>30 mM). The biomimetic elucidation for orchestrating the allocation of gradient concentration of Mg²⁺ in accordance of the physiological condition is crucial for designing the accurate microenvironment in osteochondral injury defects for optimization of bone and cartilage repairing materials in the future. Full article

In recent years, significant progress has been made in the development of new technologies to meet the demand for engineered interfaces with appropriate properties for osteochondral unit repair and regeneration. In this context, we combined two methodologies that have emerged as powerful approaches for tissue engineering application: electrospinning to fabricate a nanofibrous polymeric scaffold and pulsed laser deposition to tune and control the composition and morphology of the scaffold surface. A multi-component scaffold composed of synthetic and natural polymers was proposed to combine the biocompatibility and suitable mechanical properties of poly(D,L-lactic acid) with the hydrophilicity and cellular affinity of gelatin. As part of a biomimetic strategy for the generation of bi-functional scaffolds, we coated the electrospun fibers with a thin film of a bioactive glass–ceramic material supplemented with manganese ions. The physico-chemical properties and composition of the bi-layered scaffold were investigated, and its bioactivity, in terms of induced mineralization, was tested by incubation in a simulated body fluid buffer. The processes of the inorganic film dissolution and the calcium phosphate phases growth were followed by microscopic and spectroscopic techniques, confirming that a combination of bioactive glass–ceramics and nanofibrous scaffolds has promising potential in the regeneration of osteochondral tissue due to its ability to induce mineralization in connective tissues. Full article

Tissue engineering aims at developing complex composite scaffolds for articular cartilage repair. These scaffolds must exhibit a mechanical behavior similar to the whole osteochondral unit. In situ spherical indentation allows us to map the mechanical behavior of articular cartilage, avoiding removal of the underlying bone tissue. Little is known about the impact of grid spacing, indenter diameter, and induced deformation on the cartilage response to indentation. We investigated the impact of grid spacing (range: a to 3a, where a is the radius of the contact area between cartilage and indenter), indenter diameter (range: 1 to 8 mm), and deformation induced by indentation (constant indentation depth versus constant nominal deformation) on cartilage response. The bias induced by indentations performed in adjacent grid points was minimized with a 3a grid spacing. The cartilage response was indenter-dependent for diameters ranging between 1 and 6 mm with a nominal deformation of 15%. No significant differences were found using 6 mm and 8 mm indenters. Six mm and 8 mm indenters were used to map human articular cartilage with a grid spacing equal to 3a. Instantaneous elastic modulus E₀ was calculated for constant indentation depth and constant nominal deformation. E₀ value distribution did not change significantly by switching the two indenters, while dispersion decreased by 5–6% when a constant nominal deformation was applied. Such an approach was able to discriminate changes in tissue response due to doubling the indentation rate. The proposed procedure seems to reduce data dispersion and properly determine cartilage mechanical properties to be compared with those of complex composite scaffolds. Full article