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The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 4 | Pages 435 - 438
1 Apr 2011
Gilbody J

Aseptic loosening of the acetabular component continues to be the most common indication for revision of total hip replacements in younger patients. Early in the evolution of the cemented hip, arthroplasty surgeons switched from removal to retention of the acetabular subchondral bone plate, theorising that unfavourable mechanical forces were the cause of loosening at the bone-cement interface. It is now known that the cause of aseptic loosening is probably biological rather than mechanical and removing the subchondral bone plate may enhance biological fixation of cement to bone. With this in mind, perhaps it is time to revive removal of the subchondral bone as a standard part of acetabular preparation


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 72 - 72
1 Mar 2006
Flivik G Kristianssson I Kesteris U Ryd L
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In a prospective, controlled clinical study we randomised 50 patients with primary coxarthrosis into either removal or retention of the subchondral bone plate during ace-tabular preparation in cemented total hip arthroplasty. The effect was evaluated for a 2-year follow up period by repeated RSA examinations, analyses of radiolucent lines on conventional radiographs and clinical follow-ups with WOMAC, SF-12 and Harris Hip Score. Removal of the subchondral bone plate resulted in an improvement in radiological appearance of the bone-cement interface. For the retention group the extent of radiolucent lines as measured on pelvic and AP-view, had increased from a direct postoperative average level of 3.4% to a 2-year level of 28.8%. For the group with removal of the subchondral bone plate, the direct postoperative radiographs revealed no radiolucency, and at 2 years it only occupied a mean of 4.1 % of the interface. With the classification according to Hodgkinson the retention group had 10 out of 25 patients remaining in grade 0 (no demarcation) at 2years, whereas the removal group had 23 out of 25 patients in grade 0 at 2 years. The RSA results showed small early migration in both groups, but a tendency towards better stability and less scatter of the results in the removal group. The retention group tilted from 6 months onwards slightly but continuously towards a more horizontal position, whereas the removal group stabilized in a slightly vertical position after 1 year. The mean proximal migrations for all cups taken together were 0.09 mm at 2 years with no significant difference between groups. No differences were found in clinical outcome neither pre- nor postoperatively. To optimize the bone-cement interface and thereby increase the long time cup survival, removal of the subchondral bone plate where possible appears to be advantageous, but it is a more demanding surgical technique


Bone & Joint Research
Vol. 12, Issue 12 | Pages 734 - 746
12 Dec 2023
Chen M Hu C Hsu Y Lin Y Chen K Ueng SWN Chang Y

Aims. Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown. Methods. We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators. Results. EDIL3 protein prevented chondrocyte clustering and maintained chondrocyte number and SOX9 expression in the human cartilage plug. Administration of EDIL3 protein prevented OA progression in STR/ort mice by maintaining the number of chondrocytes in the hyaline cartilage and the number of matrix-producing chondrocytes (MPCs). It reduced the degradation of aggrecan, the expression of matrix metalloproteinase (MMP)-13, the Osteoarthritis Research Society International (OARSI) score, and bone remodelling. It increased the porosity of the subchondral bone plate. Administration of an EDIL3 antibody increased the number of matrix-non-producing chondrocytes (MNCs) in cartilage and exacerbated the serum concentrations of OA-related pro-inflammatory cytokines, including monocyte chemotactic protein-3 (MCP-3), RANTES, interleukin (IL)-17A, IL-22, and GROα. Administration of β1 and β3 integrin agonists (CD98 protein) increased the expression of SOX9 in OA mice. Hence, EDIL3 might activate β1 and β3 integrins for chondroprotection. EDIL3 may also protect cartilage by attenuating the expression of IL-1β-enhanced phosphokinase proteins in chondrocytes, especially glycogen synthase kinase 3 alpha/beta (GSK-3α/β) and phospholipase C gamma 1 (PLC-γ1). Conclusion. EDIL3 has a role in maintaining the cartilage ECM and inhibiting the development of OA, making it a potential therapeutic drug for OA. Cite this article: Bone Joint Res 2023;12(12):734–746


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_8 | Pages 9 - 9
11 Apr 2023
Angrisani N Willumeit-Römer R Windhagen H Scheper V Wiese B Mavila B Helmholz H Reifenrath J
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There is no optimal therapy to stop or cure chondral degeneration in osteoarthritis (OA). Beside cartilage, subchondral bone is involved. The often sclerotic bone is mechanically less solid which in turn influences negatively chondral quality. Microfracturing as therapeutic technique aims to enhance bone quality but is applied only in smaller cartilage lesions. The osteoproliferative properties of Magnesium (Mg) have been shown repeatedly1-3. The present study examined the influence of micro-scaled Mg cylinders compared to sole drilling in an OA model.

Ten New Zealand White rabbits underwent anterior crucial ligament transection. During 12 weeks after surgery, the animals developed OA as previously described4. In a second surgery, half of the animals received 20 drill holes (ø 0.5mm) and the other half received 20 drill holes, which were additionally filled with one Mg cylinder each. Extracapsular plication was performed in all animals. During the follow-up of 8 weeks three µ-computed tomographic (µCT) scans were performed: immediately after surgery and after four and eight weeks. Changes of bone volume, trabecular thickness and bone density were calculated and compared.

µCT evaluation showed an increase in bone volume and trabecular thickness in both groups. This increase was significantly higher in rabbits which received Mg cylinders showing thrice as high values for both parameters (bone volume: Mg group +44.5%, drilling group +15.1%, p≤0.025; trabecular thickness: Mg group +53.2%, drilling group +16.9%, p≤0.025). Also bone density increased in both groups, but on a distinctly lower level and with no significant difference.

Although profound higher bone volume was found after implantation of Mg cylinders, µCT showed similar levels of bone density indicating adequate bone quality in this OA model. Macroscopic and histological evaluation of cartilage condition have to reveal possible impact on OA progression. Additionally, current examination implement different alloys and influence on lameness.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 14 - 14
2 Jan 2024
Helmholz H Chathoth BM Angrisani N Reifenrath J Willumeit-Römer R
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Osteoarthritis (OA) is an inflammatory disease affecting the complete synovial joint including the cartilage layer and the subchondral bone plate. Due to the multifactorial causes and the not yet completely resolved molecular mechanisms, it lacks a gold standard treatment to mitigate OA. Hence, biomaterials capable of delaying or preventing OA are a promising alternative or supplement to antiphlogistic and surgical interventions. Magnesium (Mg) and its alloys are among the promising biomaterials with osteoinductive effects. This work investigated the impact of Mg micro cylinders (length ≈of 1.0 mm and width of 0.5 mm) in vitro, in favoring joint regeneration together with preventing OA progression. Therefore, a mesenchymal stem cell line (SCP-1) was applied in order to assess the compatibility of the degradable material. Furthermore, an in vitro OA model utilizing SCP-1 cells based on the supplementation of the cytokines; IL-1β, TNF-α was established and disclosed the capability of Mg microparticles in differentiating SCP-1 cells into chondrogenic and osteogenic lineages proven through extracellular matrix staining and gene marker analysis. A concentration above 10 mM revealed a reduction in the cell viability by 50 %. An increase in the expression of collagens especially and proteoglycans (COL2A1, Aggrecan) as extracellular matrix proteins as well as an increase in osteogenic marker (ALP, BMP2) favoring the mineralization process were observed. The inflammatory condition reduced the viability and productivity of the applied stem cell line. However, the application of Mg microparticles induced a cell recovery and reduction of inflammation marker such as MMP1 and IL6. The cytocompatible and the ability of Mg microparticles in supporting bone and cartilage repair mechanisms in vitro even under inflammatory conditions make biodegradable Mg microparticles a suitable implant material to treat OA therapy. Acknowledgements: This project OAMag was funded by the German Research Foundation (project number 404534760). The author thank Dr. Björn Wiese (hereon) for the production of Mg based material and Prof. Böcker (MUM Musculoskeletal University Center Munich) for the provision of SCP-1 cell line


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 15 - 15
4 Apr 2023
Luk J
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Many factors have been reported to affect the functional survival of OCA transplants, including chondrocyte viability at time of transplantation, rate and extent of allograft bone integration, transplantation techniques, and postoperative rehabilitation protocols and adherence. The objective of this study was to determine the optimal subchondral bone drilling technique by evaluating the effects of hole diameter on the material properties of OCAs while also considering total surface area for potential biologic benefits for cell and vascular ingrowth. Using allograft tissues that would be otherwise discarded in combination with deidentified diagnostic imaging (MRI and CT), a model of a large shell osteochondral allograft was recreated using LS-PrePost and FEBio based on clinically relevant elastic material properties for cortical bone, trabecular bone, cartilage, and hole ingrowth tissue. The 0.8 mesh size model consisted of 4 mm trabecular bone, 4 mm cortical bone, and 3 mm cartilage sections that summed to a cross-sectional area of 1600 mm2 (40 mm x 40 mm). Holes were modeled to be 4mm deep in relation to clinical practice where holes are drilled from the deep margin of subchondral trabecular bone to the cortical subchondral bone plate. To test the biomechanic variations between drill hole sizes, models with hole sizes pertinent to standard-of-care commercially available orthopaedic drill sizes of 1.1mm, 2.4 mm, or 4.0 mm holes were loaded across the top surface over a one second duration and evaluated for effective stress, effective strain, 1st principal strain, and 3rd principal strain in compressive conditions. Results measured effective stress and strain and 1st and 3rd principal strain increased with hole depth. The results of the present FEA modeling study indicate that the larger 4.0 mm diameter holes were associated with greater stresses and strains within OCA shell graft, which may render the allograft at higher risk for mechanical failure. Based on these initial results, the smaller diameter 2.4 mm and 1.1 mm holes will be further investigated to determine optimal number, configuration, and depth of subchondral drilling for OCA preparation for transplantation


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_7 | Pages 16 - 16
4 Apr 2023
Luk J
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Despite the growing success of OCA transplantation in treating large articular cartilage lesions in multiple joints, revisions and failures still occur. While preimplantation subchondral drilling is intended to directly decrease allograft bioburden and has been associated with significant improvements in outcomes after OCA transplantation, the effects of size, number, and spacing of subchondral bone drill sites have not been fully evaluated. This study aimed to investigate the effects of drill size with or without pulse-lavage of OCA subchondral bone by quantifying remnant marrow elements using histomorphometry. With IRB and ACUC approvals, human and canine OCAs were acquired for research purposes. Portions of human tibial plateau OCAs acquired from AATB-certified tissue banks that would otherwise be discarded were recovered and sectioned into lateral and medial hemiplateaus (n=2 each) with a thickness of 7 mm. Canine femoral condyles and tibial plateaus were split into lateral and medial components with a thickness of 7 mm (n=8). Using our clinical preimplantation preparation protocol, holes were drilled into the subchondral bone of each condyle and hemiplateau OCA using either 1.6 mm OD or 3.2 mm OD drill bits from the cut surface to the cortical subchondral bone plate. One femoral condyle and one hemiplateau per drill bit size were pulse-lavaged while the corresponding OCAs were not. The mean total %-fill remaining marrow elements for each treatment group was calculated. Little to no quantifiable bone marrow element retention was noted to remain within the subchondral bone of human or canine OCA specimens after subchondral drilling of allograft bone with either drill bit size evaluated and with or without pulse-lavage. The %-fill was consistent across zones, ranging from 1-5%. This project was designed to provide a preliminary histologic evaluation of the effects of drill size on OCA preimplantation preparation efficacy based on amount of remaining bone marrow elements in human and canine femoral condyle and tibial plateau specimens. Based on these initial findings, choice of drill bit size for OCA subchondral drilling may need to be based on the associated biomechanical effects rather than effects on donor bone marrow element removal


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 580 - 581
1 Nov 2011
Hurtig M Lowerison M Marks P
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Purpose:. To develop a method for depth-wise analysis of subchondral bone that considers the gradient of bone volume, density and organization between the articular surface and the marrow cavity. To understand the interplay between subchondral bone changes and extrinsic cartilage repair after microfracture. Method: Since 30% of patients fail microfracture for contained chondral lesions, our hypothesis was that early subchondral sclerosis increases compaction of bone around microfracture holes, leading to failed cartilage repair. Human osteochondral segments from the knee joint were characterized macroscopically using the Outerbridge score, then imaged at 45 micron resolution using microCT. Regions of interest (ROI) were chosen under normal cartilage and abnormal cartilage (Outerbridge Score=1). Routine Bone mineral density (BMD) analysis was performed on each ROI using GE MicroView™ analysis software. Additional depth-wise analysis of BMD was done by exporting each ROI was a density map, and calculating the mean, standard deviation and rate of change of BMD by slice in the vertical (coronal) plane. Plots of normal and early OA data by depth were compared. Microfracture holes were made in normal and sclerotic subchondral bone, and depth-wise measurements of subchondral compaction around the holes were made were made. Results: Bone under normal versus OA cartilage was very subtly different in microCT images, but ROI microCT analysis showed that the OA samples were more mineralized and contained more bone. Using the depth-wise analysis algorithm, automated detection and measurement of the subchondral bone plate and other discrete structures was possible. The depth-wise analysis confirmed that the osteoarthritic subchondral bone plate had a higher BMD and bone volume fraction, but also showed that the rate of change (gradient) in BMD was greater. Horizontally orientated trabeculae and other anomalies were found in OA bone that contributed a more variable BMD in trabecular bone at up to 5 mm from the articular surface. Bone with early sclerotic changes had significantly (p< .01) more bone volume fraction and BMD (p< .05) around microfracture holes in this ex vivo experiment. Conclusion: An enhanced picture of subchondral bone plate and trabecular bone anomalies can be appreciated using a depth-wise approach to image analysis. Both sclerosis and osteopenia have been reported in OA and models of OA, but this analysis shows that variability and gradient of BMD change adjacent to the articular cartilage is a significant feature of OA. This is consistent with some theories of OA progression that implicate stress concentration between the cartilage and subchondral bone plate leading to cartilage degeneration. More importantly, bone sclerosis has a direct effect on the amount of compaction around microfracture holes, so improvements in microfracture technique are needed to avoid this


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_15 | Pages 120 - 120
1 Nov 2018
Pyszkowski J Pouran B Mattei G Breel E
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The micro-mechanical properties of complex biomaterials play an important role in tissue engineering and regenerative medicine, by regulating cellular processes and signalling. Local characterization of complex tissues while immersed in liquids proves to be very difficult to perform. We therefore present a method to derive viscoelastic micro-mechanical properties via non-destructive nano-indentation measurements in liquid. This technique is featured with a fiber-optical ferrule-top micro-machined force transducer, enabling a wide range of mechanical tests: from quasi-static experiments to derive elastic moduli, to step-response tests (e.g. creep, stress-relaxation), dynamic mechanical analysis (DMA) and constant strain rate tests to characterize sample viscoelastic behaviour. As a complex application we here present the osteochondral (OC) interface, which gradually ranges from hard and stiff bone regions towards softer and viscoelastic articular cartilage covering joint surface. The osteochondral plugs were collected from medial femoral condyle of cadaveric knees and measured at 37°C to mimic in-vivo physiological-like conditions. The stiffness of articular cartilage was 1.58±0.06 MPa, whereas subchondral bone plate could be categorized in “softer” region with 68.24±37.43 MPa, and a “stiffer” region with 683.68±622.88 MPa. The high stiffness in the “hard” region could be attributed to the mineralized matrix in the contact area, whereas the contribution of gel-like material, containing cell processes, along with osteocytes was larger in the “soft” region of the subchondral bone plate, leading to lower stiffness. These results might correlate with differences in extracellular matrix (ECM) composition and micro-architecture and are essential for engineering functional gradient scaffolds to better understand cell-ECM interactions


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_8 | Pages 39 - 39
1 May 2019
Sharkey P
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Bone marrow lesions (BMLs), identified by MRI, are defined as a region of cancellous bone with high T2 and low T1 signal intensity. They are associated with various knee pathologies including spontaneous osteonecrosis of the knee (SPONK), AVN, trauma (fracture and bone contusion), following arthroscopy and secondary to overuse (i.e., after completing a marathon). They also are commonly recognised in patients with knee OA (referred to as OA-BMLs) and their substantial importance in knee OA pathogenesis has been recently identified. Depending upon the etiology (i.e., bone contusion, overuse, etc.) of the BML, these lesions can be “acute” in nature and spontaneously resolve over time. However, OA-BMLs generally are considered to be a “chronic” condition and overtime they have been shown to often persist and increase in size. Retrieval studies following THA and TKA, in patients with a preoperatively identified BML, have greatly expanded our understanding of OA – BMLs and these investigations consistently identify the critical role subchondral bone plays in OA disease progression. Histologic, histochemical and mechanical studies of OA-BMLs demonstrate significant alternations from healthy subchondral bone. The effected bone contains regions where fibrous tissue has replaced cancellous bone, microfractures are present and vascularity is increased. There is an increased concentration of inflammatory mediators and the bone structural integrity is compromised. Standard radiographs of the knee correlate only modestly with patient symptoms, but conversely, the presence of an OA-BML is an extremely strong predictor of pain and knee joint dysfunction. Felson et al. reported this relationship. In a large group of patients with painful knee OA, 77.5% of these patients had a BML. Both the presence and size of the BML, following multiregression analysis, were significant predictors of knee pain severity. Additionally, likely secondary to inadequate subchondral bone plate support, the presence of an OA-BML is associated with subchondral bone attrition (SBA). SBA leads to collapse of the subchondral bone plate and progressive joint deformity. Based on the association of an OA-BML with pain, joint dysfunction and deformity, it is not surprising that these lesions are prognostic for patients seeking knee arthroplasty. Several studies have demonstrated that the odds of knee arthroplasty performance are substantially higher in patents with an OA-BML. This enhanced understanding of knee OA pathogenesis and the critical role of subchondral bone in this process creates an opportunity for development of novel prevention and treatment strategies. Prevention of OA-BML formation has been considered and pharmacologic interventions proposed. Recent studies have reported positive results for treatment with bisphosphonates in patients with knee OA. One study reported significant pain and OA-BML size reduction in patients receiving a bisphosphonate for 4 months. A strategy aimed at repairing and/or enhancing subchondral bone compromised by an OA-BML has also been proposed. Early results reported with this intervention are encouraging, but preliminary


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 80 - 80
1 Jan 2017
Renz Y Seebach M Hesse E Lotz B Blunk T Berberich O Richter W
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Long-term regeneration of cartilage defects treated with tissue engineering constructs often fails because of insufficient integration with the host tissue. We hypothesize that construct integration will be improved when implants actively interact with and integrate into the subchondral bone. Growth and Differentiation Factor 5 (GDF-5) is known to support maturation of chondrocytes and to enhance chondrogenic differentiation and hypertrophy of mesenchymal stromal cells (MSC). Therefore, we investigated whether GDF-5 is capable to stimulate endochondral ossification of MSC in vitro and in vivo and would, thus, be a promising candidate for augmenting fibrin glue in order to support integration of tissue engineering constructs into the subchondral bone plate. To evaluate the adhesive strength of fibrin glue versus BioGlue. ®. , a commercially available glue used in vascular surgery, an ex vivo cadaver study was performed and adhesion strength was measured via pull-out testing. MSC were suspended in fibrin glue and cultivated in chondrogenic medium with and without 150 ng/mL GDF-5. After 4 weeks, the formed cartilage was evaluated and half of the constructs were implanted subcutaneously into immunodeficient mice. Endochondral ossification was evaluated after 2 and 4 weeks histologically and by microCT analysis. BioGlue. ®. and GDF-5-augmented fibrin glue were tested for 4 weeks in a minipig cartilage defect model to assess their orthotopic biocompatibility. Pull-out testing revealed sufficient adhesive strength of fibrin glue to fix polymeric CellCoTec constructs in 6 mm cartilage defects, however, BioGlue. ®. showed significantly higher adhesive power. In vitro chondrogenesis of MSC under GDF-5 treatment resulted in equal GAG deposition and COLIIa1 and ACAN gene expression compared to controls. Importantly, significantly increased ALP-activity under treatment with GDF-5 on day 28 indicated enhanced hypertrophic differentiation compared to controls. In vivo, MSC-fibrin constructs pre-cultured with GDF-5 developed a significantly higher bone volume on day 14 and 28 compared to controls. When pre-cultured with GDF-5 constructs showed furthermore a significantly higher bone compactness (bone surface/bone volume coefficient) than controls, and thus revealed a higher maturity of the formed bone at 2 weeks and 4 weeks. Orthotopic biocompatibility testing in minipigs showed good defect filling and no adverse reactions of the subchondral bone plate for defects treated with GDF-5-augmented fibrin glue. Defects treated with BioGlue. ®. , however, showed considerable subchondral bone lysis. Thus, BioGlue. ®. – despite its adhesive strength – should not be used for construct fixation in cartilage defects. GDF-5-augmented fibrin glue is considered promising, because of a combination of the adhesive strength of fibrin with an enhanced osteochondral activity of GDF-5 on MSC. Next step is to perform a large animal study to unravel whether GDF-5 stimulated endochondral ossification can improve scaffold integration in an orthotopic cartilage defect model


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 75 - 75
1 Mar 2021
Mendes L Bosmans K Maréchal M Luyten F
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Joint surface restoration of deep osteochondral defects represents a significant unmet clinical need. Moreover, untreated lesions lead to a high rate of osteoarthritis. The current strategies to repair deep osteochondral defects such as osteochondral grafting or sandwich strategies combining bone autografts with ACI/MACI fail to generate long-lasting osteochondral interfaces. Herein, we investigated the capacity of juvenile Osteochondral Grafts (OCGs) to repair osteochondral defects in skeletally mature animals. With this regenerative model in view, we set up a new biological, bilayered, and scaffold-free Tissue Engineered (TE) construct for the repair of the osteochondral unit of the knee. Skeletally immature (5 weeks old) and mature (11 weeks old) Lewis rats were used. Cylindrical OCGs were excised from the intercondylar groove of the knee of skeletally immature rats and transplanted into osteochondral defects created in skeletally mature rats. To create bilayered TE constructs, micromasses of human periosteum-derived progenitor cells (hPDCs) and human articular chondrocytes (hACs) were produced in vitro using chemically defined medium formulations. These constructs were subsequently implanted orthotopically in vivo in nude rats. At 4 and 16 weeks after surgery, the knees were collected and processed for subsequent 3D imaging analysis and histological evaluation. Micro-computed tomography (µCT), H&E and Safranin O staining were used to evaluate the degree of tissue repair. Our results showed that the osteochondral unit of the knee in 5 weeks old rats exhibit an immature phenotype, displaying active subchondral bone formation through endochondral ossification, the absence of a tidemark, and articular chondrocytes oriented parallel to the articular surface. When transplanted into skeletally mature animals, the immature OCGs resumed their maturation process, i.e., formed new subchondral bone, partially established the tidemark, and maintained their Safranin O-positive hyaline cartilage at 16 weeks after transplantation. The bilayered TE constructs (hPDCs + hACs) could partially recapitulate the cascade of events as seen with the immature OCGs, i.e., the regeneration of the subchondral bone and the formation of the typical joint surface architecture, ranging from non-mineralized hyaline cartilage in the superficial layers to a progressively mineralized matrix at the interface with a new subchondral bone plate. Cell-based TE constructs displaying a hierarchically organized structure comprising of different tissue forming units seem an attractive new strategy to treat osteochondral defects of the knee


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_12 | Pages 34 - 34
1 Mar 2013
Phillips G Lee P Robertson A Lyons K Forster M
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The TruFit® plug is a cylindrical scaffold designed to bridge defects in articular cartilages. It is a porous structure with interconnected pores, which gives it the capability of providing a framework for the ingrowth new tissue and remodelling to articular cartilage and bone. The aim of this study was to assess the radiological incorporation of TruFit® Plugs using MRI. Between December 2007 & August 2009, 22 patients underwent treatment of a chondral or osteochondral lesion using one or more TruFit Plugs. At a minimum of 2 years, 10 patients (12 lesions) were MRI scanned and assessed with a modified MOCART Scoring system by an independent Consultant Musculoskeletal Radiologist. 8 patients were no longer contactable and 4 patients declined MRI as their knee was asymptomatic. 8 of 12 lesions showed congruent articular cartilage cover with a surface of a similar thickness and signal to the surrounding cartilage and reconstitution of the subchondral bone plate. 2 lesions had a thicker congruent articular surface with a similar signal to the surrounding articular cartilage without restoration of the subchondral bone plate. 2 lesions showed no graft incorporation at all and were filled with granulation tissue. Full incorporation of the bony portion of the plug had occurred in only 3 lesions with partial incorporation in 7 lesions. The remaining portion of these 7 lesions looked cystic on MRI. The MRI appearances of the TruFit® Plug at 2 years are encouraging with the majority (83%) showing good restoration of the articular surface with tissue of similar thickness, congruity and signal as the surrounding articular cartilage. However complete incorporation of the TruFit® Plug is rare and cystic change is common. The significance of this cystic change is not clear


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 95 - 95
1 Jul 2014
Florea C Malo M Rautiainen J Mäkelä J Nieminen M Jurvelin J Davidescu A Korhonen R
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Summary. In a rabbit model of early osteoarthritis, structural changes in femoral condyle cartilage were severer in the lateral compartment and preceded alterations in the underlying bone. In the medial compartment, altered bone properties occurred together with structural changes in cartilage. Introduction. Early osteoarthritic changes in cartilage have been previously studied through anterior cruciate ligament transection (ACLT) in rabbits. However, parallel changes in the structure of subchondral and trabecular bone at 4 weeks after ACLT are not known. Methods. Skeletally mature 14-month old New Zealand white rabbits (n=8) underwent ACLT in the left knee, while right knees were used as controls (CTRL). Femoral condyles (FCs) were harvested at 4 weeks after ACLT. INDENTATION TESTING. Stepwise stress-relaxation tests were performed on medial and lateral FC cartilage (100%/s ramp rate, 3×5% step, 15 min relaxation time). Sinusoidal loading was then applied (amplitude 4% of thickness, 1Hz, 4 cycles). Equilibrium (Eeq) and dynamic (Ed) moduli were derived from stress-relaxation and sinusoidal tests, respectively. STRUCTURAL ANALYSIS OF CARTILAGE. Polarised light microscopy (PLM) and digital densitometry (DD) were used to analyze the collagen orientation angle (COA) and proteoglycan content in the cartilage samples. STRUCTURAL ANALYSIS OF BONE. Distal compartments of FCs were scanned using a high-resolution µCT scanner (Skyscan 1172, Belgium) with an isotropic voxel size of 25 µm. µCT data were imported into Mimics (Materialise, Belgium) for segmentation. 2×2×4 mm. 3. volumes of interest (VOIs) were placed in weight-bearing regions of medial and lateral FCs. Subchondral bone plate thickness (Pt.Th), trabecular volume fraction (BV/TV), trabecular thickness (Tb.Th), structural model index (SMI) and trabecular separation (Tb.Sp) were calculated using the CTAnalyzer software (Skyscan) from the VOIs. STATISTICAL TESTS. Mixed linear model for cartilage parameters and Wilcoxon signed-rank test for bone parameters were used to compare ACLT and CTRL groups (p < 0.05). Results. In both lateral and medial FC compartments, Eeq was significantly smaller in ACLT than in CTRL cartilage. In the medial compartment, also Ed was significantly smaller in ACLT than in CTRL cartilage. As a result of ACLT, significant alterations in the COA extended deeper into cartilage in the lateral than medial compartment, while proteoglycan content was reduced significantly and similarly in both lateral and medial FC cartilages. After ACLT, Pt.Th was significantly reduced in the medial compartment, while no changes were observed in the lateral compartment. Furthermore, only in the medial compartment, both BV/TV and Tb.Th were significantly smaller in the ACLT compared to the CTRL group. Discussion. The study showed that disruption of the collagen architecture in the ACLT joint cartilage extended into the middle zone only in the lateral FC compartment. Instead, thinning of the subchondral bone plate combined with resorption of trabecular bone was observed only in the medial FC compartment. The former finding reflects early osteoarthritic changes, while the latter finding may be indicative of a diminished loading in the medial FC compartment, as caused by ACLT


The Journal of Bone & Joint Surgery British Volume
Vol. 46-B, Issue 3 | Pages 530 - 538
1 Aug 1964
Crock HV

1. Sixteen patients with articular cartilage erosions after slight injury have been described, as have the results of their treatment. 2. The clinical features of this rarely diagnosed condition are discussed. Attention is drawn to "articular crepitus" and "synovial crepitus" as useful physical signs in establishing the diagnosis. 3. A radiographic sign of localised subarticular osteoporosis is reported and discussed. 4. The surgical treatment used was either shaving of the affected area of cartilage or a combination of shaving with drilling of the subchondral bone plate


Bone & Joint Research
Vol. 12, Issue 9 | Pages 536 - 545
8 Sep 2023
Luo P Yuan Q Yang M Wan X Xu P

Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.

Cite this article: Bone Joint Res 2023;12(9):536–545.


Bone & Joint Research
Vol. 11, Issue 3 | Pages 162 - 170
14 Mar 2022
Samvelyan HJ Huesa C Cui L Farquharson C Staines KA

Aims

Osteoarthritis (OA) is the most prevalent systemic musculoskeletal disorder, characterized by articular cartilage degeneration and subchondral bone (SCB) sclerosis. Here, we sought to examine the contribution of accelerated growth to OA development using a murine model of excessive longitudinal growth. Suppressor of cytokine signalling 2 (SOCS2) is a negative regulator of growth hormone (GH) signalling, thus mice deficient in SOCS2 (Socs2-/-) display accelerated bone growth.

Methods

We examined vulnerability of Socs2-/- mice to OA following surgical induction of disease (destabilization of the medial meniscus (DMM)), and with ageing, by histology and micro-CT.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 237 - 237
1 Nov 2002
Hart JAL Paddle-Ledinek J
Full Access

Purpose: To define the role of ACI in treatment of cartilage defects in the knee joint. Method: 106 articular cartilage defects in 79 knees of 77 patients were treated by ACI as described by Brittberg et al, 1994. 43.5% of the lesions involved the patella, 35.2% the femoral condyles, 16.7% the trochlea, and 4.6% the tibial condyles. 20% of knees had more than one defect. Associated biomechanical procedures were carried out in 88.7%. Results: 70 lesions in 58 knees and 56 patients were assessed arthroscopically 9 months after implantation; 4 eligible patients were not assessed. The average ICRS repair score (maximum 12) was as follows: tibial condyle 11.5, (4 defects); patella 11.3, (32 defects); femoral condyle 11.0, (23 defects) and trochlea 10.7, (11 defects). Synovitis was markedly reduced in all knees with well healed defects. Contraindications to ACI in this series were:. Non-contained defects,. Bi-polar lesions,. Patients greater than 45 years,. Uncorrected biomechanics,. Regional pain syndrome type 1,. Limited joint movement,. Defective subchondral bone plate. Conclusion: ACI effectively repairs articular cartilage defects in the knee joint, provided that the contraindications are recognised. Unlike other series, the results for the patella, patellofemoral joint have matched those for the femoral condyle. This is attributed to the simultaneous biomechanical correction of the patellofemoral joint. Stabilisation of the articular surface results in resolution of synovitis


Bone & Joint Research
Vol. 12, Issue 10 | Pages 654 - 656
16 Oct 2023
Makaram NS Simpson AHRW

Cite this article: Bone Joint Res 2023;12(10):654–656.