Introduction and Aims: Cartilage injury often leads to secondary osteoarthritis. However, the progression of cartilage lesions after injury has not been fully documented. Factors predictive of the rate and severity of progression are largely unknown. This study analysed the relationship between arthroscopic, histologic, and magnetic resonance imaging findings after acute joint trauma. Method: Twenty patients were recruited into the study at a mean three months after acute knee injury. Each patient underwent cartilage-specific magnetic resonance imaging (MRI) sequences of the affected knee after injury and at six months, one year, and two years after arthroscopy. Cartilage lesions were graded on MRI and arthroscopy. Synovial fluid was sampled, and a 1.8 mm biopsy was obtained from the edge of cartilage lesion. Control biopsies were obtained from fresh cadaver donors. Cells undergoing DNA fragmentation in biopsies were counted. Results: All cases of partial or full thickness cartilage loss were detected by MRI. Biopsies from cartilage lesions had significantly more cells undergoing DNA fragmentation (41%) than control biopsies (12%), suggesting apoptotic cell death. On MRI follow-up, cartilage lesion grade improved in five patients, worsened in two, and did not change in 13 patients. The percentage of cells undergoing DNA fragmentation correlated significantly with keratan sulfate levels in synovial fluid (R = 0.68). Keratan sulfate levels were markedly higher in knees with progressive lesions (72 vs. 31 microgm/ml). Conclusion: Cartilage cell viability can directly impact the potential for repair. The development of accurate markers that may predict the eventual fate of the lesion is of tremendous clinical value. Elevated levels of matrix degradation products such as keratan sulfate can be predictive of a poorer prognosis

Cartilage injury is generally associated with cytokine release and accumulation of reactive oxygen species. These mediators trigger pathologic behaviour of the surviving chondrocytes, which respond by excessive expression of catabolic enzymes, such as matrix metalloproteinase 13 (MMP-13), reduced synthesis of type II collagen (COL2A1) and apoptosis. In the long run, these pathologic conditions can cause a posttraumatic osteoarthritis. With the objective to attenuate the progressive degradation of the extracellular matrix and, what is more, promote chondroanabolic processes, a multidirectional treatment of trauma-induced pathogenesis was tested for the first time. Therefore, we evaluated the combinations of one anabolic growth factor (IGF-1, FGF18 or BMP7) with the antioxidant N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma model and compared the findings with the corresponding monotherapy. Human cartilage tissue was obtained with informed consent from donors undergoing knee joint replacement (n=24). Only macroscopically intact tissue was used to prepare explants. Cartilage explants were subjected to a blunt impact (0.59 J) by a drop-tower and treated by IGF-1 [100 ng/mL], FGF18 [200 ng/mL] or BMP7 [100 ng/mL] and/or NAC [2 mM] for 7 days. Following parameters were analysed: cell viability (live/dead staining), gene expression (qRT-PCR) as well as biosynthesis (ELISA) of type II collagen and MMP-13. For statistical analysisKruskal-Wallis or One-way ANOVA was used. All data were collected in the orthopedic research laboratory of the University of Ulm, Germany. Trauma-induced cell death was completely prevented by NAC treatment and FGF18 or BMP7 to a large extent, respectively (p<0.0001). IGF-1 exhibited only poor cell protection. Combination of NAC and FGF18 or BMP7 did not result in enhanced effectiveness; however, IGF-1 significantly reduced NAC-mediated cell protection. While IGF-1 or BMP7 induced collagen type II gene expression (p=0.0069 and p<0.0001, respectively) and its biosynthesis (p<0.0001 and p=0.0131, respectively), NAC or FGF18 caused significant suppression of this matrix component (each p<0.001). Although COL2A1 mRNA was significantly increased by NAC plus IGF-1 (p<0.0001), biosynthesis of collagen type II was generally abolished after multidirectional treatment. Except for IGF-1, all tested therapeutics exhibited chondroprotective qualities, as demonstrated by attenuated MMP-13 expression and breakdown of type II collagen. In combination with IGF-1, NAC-mediated chondroprotection was reduced. Overall, both chondroanabolic and antioxidative therapy had individual advantages. Since adverse interactions were found by simultaneous application of the therapeutics, a sequential approach might improve the efficacy. In support of this strategy current experiments showed that though cell and chondroprotective effects of NAC were maintained after withdrawal of the antioxidant, type II collagen expression recovered by time

Aims

The aim of this study was to report the pooled prevalence of post-traumatic osteoarthritis (PTOA) and examine whether the risk of developing PTOA after anterior cruciate ligament (ACL) injury has decreased in recent decades.

Summary Statement

The implantation of scaffold-free CTE from suspension culture into growth-plate defects resulted in a significant reduction in growth arrest of the rabbit tibia

Meniscal repairs are commonly performed during anterior cruciate ligament (ACL) reconstruction. This study aimed to identify the risk factors for meniscal repair failure following concurrent primary ACL reconstruction. Primary ACL reconstructions with a concurrent repair of a meniscal tear recorded in the New Zealand ACL Registry between April 2014 and December 2018 were analyzed. Meniscal repair failure was defined as a patient who underwent subsequent meniscectomy, and was identified after cross-referencing data from the ACL Registry with the national database of the Accident Compensation Corporation (ACC). Multivariate Cox regression was performed to produce hazard ratios (HR) with 95% confidence intervals (CI) to identify the patient and surgical risk factors for meniscal repair failure. 2041 meniscal repairs were analyzed (medial = 1235 and lateral = 806). The overall failure rate was 9.4% (n = 192). Failure occurred in 11.1% of medial (137/1235) and 6.8% of lateral (55/806) meniscal repairs. The risk of medial failure was higher with hamstring tendon autografts (adjusted HR = 2.00, 95% CI 1.23 – 3.26, p = 0.006) and in patients with cartilage injury in the medial compartment (adjusted HR = 1.56, 95% CI 1.09 – 2.23, p = 0.015). The risk of lateral failure was higher when the procedure was performed by a surgeon with an annual case volume of less than 30 ACL reconstructions (adjusted HR = 1.92, 95% CI 1.10 – 3.33, p = 0.021). Age, gender, time from injury-to-surgery and femoral tunnel drilling technique did not influence the risk of meniscal repair failure. When repairing a meniscal tear during ACL reconstruction, the use of a hamstring tendon autograft or the presence of cartilage injury in the medial compartment increases the risk of medial meniscal repair failure. Lower surgeon case volume increases the risk of lateral meniscal repair failure

Background. Anterior cruciate ligament (ACL) reconstruction with concomitant meniscal injury occurs frequently. Meniscal repair is associated with improved long-term outcomes compared to resection but is also associated with a higher reoperation rate. Knowledge of the risk factors for repair failure may be important in optimizing patient outcomes. Purpose. This study aimed to identify the patient and surgical risk factors for meniscal repair failure, defined as a subsequent meniscectomy, following concurrent primary ACL reconstruction. Methods. Data recorded by the New Zealand ACL Registry and the Accident Compensation Corporation, the New Zealand Government's sole funder of ACL reconstructions and any subsequent surgery, was reviewed. Meniscal repairs performed with concurrent primary ACL reconstruction was included. Root repairs were excluded. Univariate and multivariate survival analysis was performed to identify the patient and surgical risk factors for meniscal repair failure. Results. Between 2014 and 2020, a total of 3,024 meniscal repairs were performed during concurrent primary ACL reconstruction (medial repair = 1,814 and lateral repair = 1,210). The overall failure rate was 6.6% (n = 201) at a mean follow-up of 2.9 years, with a failure occurring in 7.8% of medial meniscal repairs (142 out of 1,814) and 4.9% of lateral meniscal repairs (59 out of 1,210). The risk of medial failure was higher in patients with a hamstring tendon autograft (adjusted HR = 2.20, p = 0.001), patients aged 21–30 years (adjusted HR = 1.60, p = 0.037) and in those with cartilage injury in the medial compartment (adjusted HR = 1.75, p = 0.002). The risk of lateral failure was higher in patients aged ≤ 20 years (adjusted HR = 2.79, p = 0.021) and when the procedure was performed by a surgeon with an annual ACL reconstruction case volume of less than 30 (adjusted HR = 1.84, p = 0.026). Conclusion. When performing meniscal repair during a primary ACL reconstruction, the use of a hamstring tendon autograft, younger age and the presence of concomitant cartilage injury in the medial compartment increases the risk of medial meniscal repair failure, whereas younger age and low surgeon volume increases the risk of lateral meniscal repair failure

Aims. Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model. Methods. A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM. +. ) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM. +. using immunohistochemistry and immunofluorescence. Results. A total of 12 weeks after treatment, 0.5 μg/μl rHAM. +. brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion. We found that 0.5 μg/μl rHAM. +. induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment. Cite this article: Bone Joint Res 2023;12(10):615–623

Aims. Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury. Methods. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm. 2. ) were included in this study. UPAL gel was implanted into chondral defects after performing bone marrow stimulation technique, and assessed for up to three years postoperatively. The primary outcomes were the feasibility and safety of the procedure. The secondary outcomes were self-assessed clinical scores, arthroscopic scores, tissue biopsies, and MRI-based estimations. Results. No obvious adverse events related to UPAL gel implantation were observed. Self-assessed clinical scores, including pain, symptoms, activities of daily living, sports activity, and quality of life, were improved significantly at three years after surgery. Defect filling was confirmed using second-look arthroscopy at 72 weeks. Significantly improved MRI scores were observed from 12 to 144 weeks postoperatively. Histological examination of biopsy specimens obtained at 72 weeks after implantation revealed an extracellular matrix rich in glycosaminoglycan and type II collagen in the reparative tissue. Histological assessment yielded a mean overall International Cartilage Regeneration & Joint Preservation Society II score of 69.1 points (SD 10.4; 50 to 80). Conclusion. This study provides evidence supporting the safety of acellular UPAL gel implantation in facilitating cartilage repair. Despite being a single-arm study, it demonstrated the efficacy of UPAL gel implantation, suggesting it is an easy-to-use, one-step method of cartilage tissue repair circumventing the need to harvest donor cells. Cite this article: Bone Joint J 2023;105-B(8):880–887

Introduction and Objective. Regeneration of cartilage injuries is greatly limited. Therefore, cartilage injuries are often the starting point for later osteoarthritis. In the past, various bioactive glass (BG) scaffolds have been developed to promote bone healing. Due to the fact that they induce the deposition of hydroxyapatite (HA) -the main component of bone matrix, these BG types are not suitable for chondrogenesis. Hence, a novel BG (Car12N) lacking HA formation, was established. Since BG are generally brittle the combination with polymers is helpful to achieve suitable biomechanic stability. The aim of this interdisciplinary project was to investigate the effects of biodegradable polymer Poly(D,L-lactide-co-glycolide) (PLLA) infiltration into a Car12N scaffold for cartilage tissue engineering. Materials and Methods. BG scaffolds were infiltrated with PLLA using phase separation within a solvent. Pure BG Car12N scaffolds served as control. To assess whether the polymer was homogeneously distributed the polymer to glass ratio and pore contents in the upper, middle and lower third of the scaffolds were examined by light microscopy. For a more precise characterization of the scaffold topology, the glass strut length, the glass strut diameter and the pore circumference were also measured. Leaching tests in 0.1M HCl solution over 8 days were used to allow a gel layer formation on the scaffolds surface. Non-leached and leached scaffolds were subjected to strength testing. Cytotoxicity of the scaffolds with and without polymer was tested according to standards. Scaffolds were colonized with 27.777.8 per cm. 3. primary porcine articular chondrocytes (pACs) or primary human mesenchymal stromal cells (hMSCs), respectively. After cultivation for up to 35 days, the vitality, quantitative DNA and sulfated glycosaminoglycan (sGAG) contents per scaffold were determined. Results. The polymer distribution was not homogeneous in the scaffolds. There were significant differences in glass strut length and pore size. Leaching increased the biomechanical strength. All scaffolds were not cytotoxic. pACs and hMSCs were able to adhere to the scaffold with and without polymer and remained viable during the whole culturing period of 35 d. The DNA content was higher in the pAC colonized scaffolds with polymer than without polymer. The sGAG content was higher in hMSCs seeded scaffolds with polymer than in pACs seeded ones with polymer. Conclusions. Polymer infiltration leads to an increase in mechanical stability of Car12N scaffolds and chondrogenic cells are able to colonize these composites suggesting them as a promising

Aims. In the repair of condylar cartilage injury, synovium-derived mesenchymal stem cells (SMSCs) migrate to an injured site and differentiate into cartilage. This study aimed to confirm that histone deacetylase (HDAC) inhibitors, which alleviate arthritis, can improve chondrogenesis inhibited by IL-1β, and to explore its mechanism. Methods. SMSCs were isolated from synovium specimens of patients undergoing temporomandibular joint (TMJ) surgery. Chondrogenic differentiation potential of SMSCs was evaluated in vitro in the control, IL-1β stimulation, and IL-1β stimulation with HDAC inhibitors groups. The effect of HDAC inhibitors on the synovium and condylar cartilage in a rat TMJ arthritis model was evaluated. Results. Interleukin (IL)-1β inhibited the chondrogenic differentiation potential of SMSCs, while the HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and panobinostat (LBH589), attenuated inhibition of IL-1β-induced SMSC chondrogenesis. Additionally, SAHA attenuated the destruction of condylar cartilage in rat TMJ arthritis model. IL-6 (p < 0.001) and matrix metalloproteinase 13 (MMP13) (p = 0.006) were significantly upregulated after IL-1β stimulation, while SAHA and LBH589 attenuated IL-6 and MMP13 expression, which was upregulated by IL-1β in vitro. Silencing of IL-6 significantly downregulated MMP13 expression and attenuated IL-1β-induced chondrogenesis inhibition of SMSCs. Conclusion. HDAC inhibitors SAHA and LBH589 attenuated chondrogenesis inhibition of SMSC induced by IL-1β in TMJ, and inhibition of IL-6/MMP13 pathway activation contributes to this biological progress. This study provides a theoretical basis for the application of HDAC inhibitors in the treatment of TMJ arthritis. Cite this article: Bone Joint Res 2022;11(1):40–48

This study used a national registry to assess the outcomes of hip arthroscopy (HA) for the treatment femoroacetabular impingement (FAI). All HAs for FAI recorded in the UK Non-Arthroplasty Hip Registry (NAHR) between January 2012 and September 2023 were identified. Cases were grouped according to the index procedure performed for FAI (cam, pincer, or mixed). Patient outcomes captured included the International Hip Outcome Tool (iHOT)-12. 7,511 HAs were identified; 4,583 cam (61%), 675 pincer (9%), 2,253 mixed (30%). Mean age (34.8) was similar between groups. There was a greater proportion of females in the pincer group (75%) compared to cam (52%) and mixed (50%). A higher proportion of patients had a recorded cartilage injury in association with a cam lesion compared to pincer. The pincer group had poorer mean pre-op iHOT-12 scores (31.6 \[95%CI 29.9 to 33.3\]; n=364) compared to cam (33.7 \[95%CI 32.1 to 34.4\]; n=3,941) and achieved significantly lower scores at 12 months (pincer = 52.6 (50.2 to 55); n=249, cam = 58.3 (57.1 to 59.5); n=1,679). Overall, significant (p < 0.0001) iHOT-12 and EQ-5D improvement vs baseline pre-operative scores were achieved for all FAI subtypes at 6 months (overall mean iHOT-12 improvement +26.0 \[95%CI 25.0 to 26.9\]; n=2,983) and maintained out to 12 months (+26.2 \[25.1 to 27.2\]; n=2,760) at which point 67% and 48% of patients continued to demonstrate a score improvement greater than or equal to the minimum clinically important difference (>/=13 points) and substantial clinical benefit (>/=28 points) for iHOT-12 respectively. This study demonstrates excellent early functional outcomes following HA undertaken for FAI in a large national registry

Abstract. Introduction. Autologous chondrocyte implantation (ACI) is a common procedure, primarily performed in active, young patients to treat knee pain and functional limitations resulting from cartilage injury. Nevertheless, the functional outcomes of ACI remain poorly understood. Thus, the aim of this systematic review was to evaluate the biomechanical outcomes of ACI. Methodology. Ovid MEDLINE, Embase, and Web of Science were systematically searched using the terms ‘Knee OR Knee joint AND Autologous chondrocyte implantation OR ACI’. Strict inclusion and exclusion criteria were used to screen publications by title, abstract, and full text. Study quality and bias were assessed by two reviewers. PROSPERO ID: CRD42021238768. Results. 28 articles including 35 ACI cohorts were included in this review. The average range of motion (ROM) was found to improve with clinical significance (>5˚) and statistical significance (p < 0.05) postoperatively: 133.9 ± 5.5˚ to 139.2 ± 4.9˚ (n=12). Knee strength significantly improved within the first two postoperative years, but remained poorer than control groups at final follow-up (n=17). No statistical differences were found between ACI and control groups in their ability to perform functional activities like the 6-minute walk test. However, peak external knee extension and adduction moments during gait were significantly poorer in ACI patients when compared to controls. Conclusion. Generally, functional outcomes improved with clinical and statistical significance following ACI. However, knee strengths and external knee moments during gait remain significantly poorer than healthy controls, particularly >2-years postoperatively. Thus, ACI patients likely require targeted strength training as part of their rehabilitation programme

Abstract. Objective. The preparation of host degenerate cartilage for repair typically requires cutting and/or scraping to remove the damaged tissue. This can lead to mechanical injury and cartilage cell (chondrocytes) death, potentially limiting the integration of repair material. This study evaluated cell death at the site of cutting injury and determined whether raising the osmotic pressure (hyper-osmolarity) prior to injury could be chondroprotective. Methods. Ex vivo human femoral head cartilage was obtained from 13 patients (5 males and 8 females: 71.8 years old) with Ethical Permission and Patient consent. Cartilage wells were created using 3 or 5mm biopsy punches. Cell death at the wounded edge of the host cartilage and the edge of the extracted explants were assessed by quantifying the percentage of cell death (PCD) and measuring the width of the cell death zone at identified regions of interest (ROI) using the confocal laser scanning microscopy and image analysis software. To assess the chondroprotective effect of hyper-osmolarity, cartilage specimens were incubated in 340 or 600mOsm media, five minutes prior to injury to allow the chondrocytes to respond to the altered osmolarity. Wounded cartilage explants and cartilage wells were then cultured for a further 150 minutes following injury. Results. In 340mOsm media, the PCD around the 3mm cartilage wells was significantly less compared to the corresponding explants (20.05±10.24% vs 35.25±4.86%; P=0.0003). When using the 5mm biopsy punch, the PCD at the wound edges was significantly lower when compared to the 3mm cartilage wells (13.33±7.80% vs 20.05±10.24%; P=0.0121) at the same osmolarity. The width of the cell death zone for the well edges for both 3 and 5mm punches was significantly narrower when compared to their corresponding harvested cartilage explants in 340mOsm media (P<0.0001; P=0.0218, respectively). Exposing cartilage to raised osmolarity (600mOsm) prior to injury significantly reduced the PCD for cartilage wells produced by the 3mm biopsy punches (from 20.05±10.24% to 12.24±6.00%; P=0.0025). In addition, the zone of cell death was marginally reduced at the edges of the 5mm cartilage wells (19.25±15.78mm to 12.72±9.09mm; P=0.0499). Conclusions. The choice of biopsy punch and the osmolarity of the incubation medium prior to cartilage injury markedly affected the extent of chondrocyte death both at the edges of the cartilage wells and the explants. The smaller biopsy punch caused more chondrocyte death in the native cartilage wells compared to the larger punch, but this could be compensated for by the chondroprotective effect of raising the osmotic pressure. In general, there was less cell death at the wounded edges of the cartilage wells, compared to the explants. These results suggest that there is scope for further optimising the cutting implements used to create the cartilage wells and protecting chondrocytes by hyper-osmolarity in order to minimize cell death at cut edges and potentially enhance integration between cartilage repair material and host cartilage. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Varus malalignment increases the susceptibility of cartilage to mechanical overloading, which stimulates catabolic metabolism to break down the extracellular matrix and lead to osteoarthritis (OA). The altered mechanical axis from the hip, knee to ankle leads to knee joint pain and ensuing cartilage wear and deterioration, which impact millions of the aged population. Stabilization of the remaining damaged cartilage, and prevention of further deterioration, could provide immense clinical utility and prolong joint function. Our previous work showed that high tibial osteotomy (HTO) could shift the mechanical stress from an imbalanced status to a neutral alignment. However, the underlying mechanisms of endogenous cartilage stabilization after HTO remain unclear. We hypothesize that cartilage-resident mesenchymal stem cells (MSCs) dampen damaged cartilage injury and promote endogenous repair in a varus malaligned knee. The goal of this study is to further examine whether HTO-mediated off-loading would affect human cartilage-resident MSCs' anabolic and catabolic metabolism. This study was approved by IACUC at Xi'an Jiaotong University. Patients with medial compartment OA (52.75±6.85 yrs, left knee 18, right knee 20) underwent open-wedge HTO by the same surgeons at one single academic sports medicine center. Clinical data was documented by the Epic HIS between the dates of April 2019 and April 2022 and radiographic images were collected with a minimum of 12 months of follow-up. Medial compartment OA with/without medial meniscus injury patients with unilateral Kellgren /Lawrence grade 3–4 was confirmed by X-ray. All incisions of the lower extremity healed well after the HTO operation without incision infection. Joint space width (JSW) was measured by uploading to ImageJ software. The Knee injury and Osteoarthritis Outcome Score (KOOS) toolkit was applied to assess the pain level. Outerbridge scores were obtained from a second-look arthroscopic examination. RNA was extracted to quantify catabolic targets and pro-inflammatory genes (QiaGen). Student's t test for two group comparisons and ANOVA analysis for differences between more than 2 groups were utilized. To understand the role of mechanical loading-induced cartilage repair, we measured the serial changes of joint space width (JSW) after HTO for assessing the state of the cartilage stabilization. Our data showed that HTO increased the JSW, decreased the VAS score and improved the KOOS score significantly. We further scored cartilage lesion severity using the Outerbridge classification under a second-look arthroscopic examination while removing the HTO plate. It showed the cartilage lesion area decreased significantly, the full thickness of cartilage increased and mechanical strength was better compared to the pre-HTO baseline. HTO dampened medial tibiofemoral cartilage degeneration and accelerate cartilage repair from Outerbridge grade 2 to 3 to Outerbridge 0 to 1 compared to untreated varus OA. It suggested that physical loading was involved in HTO-induced cartilage regeneration. Given that HTO surgery increases joint space width and creates a physical loading environment, we hypothesize that HTO could increase cartilage composition and collagen accumulation. Consistent with our observation, a group of cartilage-resident MSCs was identified. Our data further showed decreased expression of RUNX2, COL10 and increased SOX9 in MSCs at the RNA level, indicating that catabolic activities were halted during mechanical off-loading. To understand the role of cartilage-resident MSCs in cartilage repair in a biophysical environment, we investigated the differentiation potential of MSCs under 3-dimensional mechanical loading conditions. The physical loading inhibited catabolic markers (IL-1 and IL-6) and increased anabolic markers (SOX9, COL2). Knee-preserved HTO intervention alleviates varus malalignment-related knee joint pain, improves daily and recreation function, and repairs degenerated cartilage of medial compartment OA. The off-loading effect of HTO may allow the mechanoregulation of cartilage repair through the differentiation of endogenous cartilage-derived MSCs

Abstract. Background. Recurrent patellar dislocation in combination with cartilage injures are difficult injuries to treat with confounding pathways of treatment. The aim of this study is to compare the clinical and functional outcomes of patients operated for patellofemoral instability with and without cartilage defects. Methods. 82 patients (mean age-28.8 years) with recurrent patellar dislocations, who underwent soft-tissue or bony procedures, were divided into 2 matched groups (age, sex, follow-up and type of procedure) of 41 each based on the presence or absence of cartilage defects in patella. Chondroplasty, microfracture, osteochondral fixation or AMIC-type procedures were done depending on the nature of cartilage injury. Lysholm, Kujala, Tegner and Subjective Knee scores of both groups were compared and analysed. Complications and return to theatre were noted. Results. With a mean follow-up of 8 years (2 years-12.3 years), there was a significant improvement observed in all the mean post-operative Patient Reported Outcome Measures (p<0.05) of both the groups, as compared to the pre-operative scores. Comparing the 2 groups, post-operative Lysholm, Kujala and Subjective knee scores were significantly higher in patients operated without cartilage defects (p<0.05). 3 patients operated for PFJ instability with cartilage defects had to undergo patellofemoral replacement in the long term. Odds ratio for developing complications is 2.6 for patients operated with cartilage defects. Conclusion. Although there is a significant improvement in the long term outcome scores of patients operated for recurrent patellar dislocation with cartilage defects, the results are significantly inferior as compared to those without cartilage defects, along with a higher risk of developing complications and returning to theatre. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Background. Recurrent patellar dislocation in combination with cartilage injures are difficult injuries to treat with confounding pathways of treatment. The aim of this study is to compare the clinical and functional outcomes of patients operated for patellofemoral instability with and without cartilage defects. Methods. 82 patients (mean age-28.8 years) with recurrent patellar dislocations, who underwent soft-tissue or bony procedures, were divided into 2 matched groups (age, sex, follow-up and type of procedure) of 41 each based on the presence or absence of cartilage defects in patella. Chondroplasty, microfracture, osteochondral fixation or Autologous Matrix-Induced Chondrogenesis(AMIC)-type procedures were done depending on the nature of cartilage injury. Lysholm, Kujala, Tegner and Subjective Knee scores of both groups were compared and analysed. Complications and return to theatre were noted. Results. With a mean follow-up of 8 years (2 years-12.3 years), there was a significant improvement observed in all the mean post-operative Patient Reported Outcome Measures (p<0.05) of both the groups, as compared to the pre-operative scores. Comparing the 2 groups, post-operative Lysholm, Kujala and Subjective knee scores were significantly higher in patients operated without cartilage defects (p<0.05). 3 patients operated for patellofemoral instability with cartilage defects had to undergo patellofemoral replacement in the long term. Odds ratio for developing complications is 2.6 for patients operated with cartilage defects. Conclusion. Although there is a significant improvement in the long term outcome scores of patients operated for recurrent patellar dislocation with cartilage defects, the results are significantly inferior as compared to those without cartilage defects, along with a higher risk of developing complications and returning to theatre

Cartilage injuries often represent irreversible tissue damage because cartilage has only a low ability to regenerate. Thus, cartilage loss results in permanent damage, which can become the starting point for osteoarthritis. In the past, bioactive glass scaffolds have been developed for bone replacement and some of these variants have also been colonized with chondrocytes. However, the hydroxylapaptite phase that is usually formed in bioglass scaffolds is not very suitable for cartilage formation (chondrogenesis). This interdisciplinary project was undertaken to develop a novel slowly degrading bioactive glass scaffold tailored for cartilage repair by resembling the native extracellular cartilage matrix (ECM) in structure and surface properties. When colonized with articular chondrocytes, the composition and topology of the scaffolds should support cell adherence, proliferation and ECM synthesis as a prerequisite for chondrogenesis in the scaffold. To study cell growth in the scaffold, the scaffolds were colonized with human mesenchymal stromal cells (hMSCs) and primary porcine articular chondrocytes (pACs) (27,777.8 cells per mm. 3. ) for 7 – 35 d in a rotatory device. Cell survival in the scaffold was determined by vitality assay. Scanning electron microscopy (SEM) visualized cell ultramorphology and direct interaction of hMSCs and pACs with the bioglass surface. Cell proliferation was detected by CyQuant assay. Subsequently, the production of sulphated glycosaminoglycans (sGAGs) typical for chondrogenic differentiation was depicted by Alcian blue staining and quantified by dimethylmethylene blue assay assay. Quantitative real-time polymerase chain reaction (QPCR) revealed gene expression of cartilage-specific aggrecan, Sox9, collagen type II and dedifferentiation-associated collagen type I. To demonstrate the ECM-protein synthesis of the cells, the production of collagen type II and type I was determined by immunolabelling. The bioactive glass scaffold remained stable over the whole observation time and allowed the survival of hMSCs and pACs for 35 days in culture. The SEM analyses revealed an intimate cell-biomaterial interaction for both cell types showing cell spreading, formation of numerous filopodia and ECM deposition. Both cell types revealed initial proliferation, decreasing after 14 days and becoming elevated again after 21 days. hMSCs formed cell clusters, whereas pACs showed an even distribution. Both cell types filled more and more the pores of the scaffold. The relative gene expression of cartilage-specific markers could be proven for hMSCs and pACs. Cell associated sGAGs deposition could be demonstrated by Alcian blue staining and sGAGs were elevated in the beginning and end of the culturing period. While the production of collagen type II could be observed with both cell types, the synthesis of aggrecan could not be detected in scaffolds seeded with hMSCs. hMSCs and pACs adhered, spread and survived on the novel bioactive glass scaffolds and exhibited a chondrocytic phenotype

To explore the relationship of hyaluronan level in synovial fluid of the knee with the degree of synovitis and cartilage injury. A total of 104 knees in 102 patients with knee osteoarthritis or other knee diseases was studied. The hyaluronan level in the synovial fluid of the knees was measured with enzyme linked immunoassay. The pathology of the synovium and articular cartilage was evaluated with Ayral’s score system and Outerbridge’s score system under arthroscopy. The data were analyzed by t’-test or nonparametric test, ANOVA, Pearson or Spearman correlation and multiple liner regression. The results showed that the hyaluronan level in the synovial fluid of the knees was correlated positively with Ayral’s score (beta’A=0.497, P< 0.001) and negatively with accumulative Outerbridge’s score (beta’O=-0.364, P< 0.001), especially Ayral’s synovitis score in 104 cases. The hyaluronan level in the synovial fluid of the knees was higher in those with Ayral’s score > and = 60 than in those with the score< 60 (P< 0.001). The hyaluronan level in the synovial fluid of the knees was lower in those with accumulative Outerbridge’s score > and = 10 than in those with the score < 10 (P< 0.05). The level of hyaluro-nan in the synovial fluid in the knees with Ayral’s score > and = 60 was correlated negatively with accumulative Outerbridge’s score (beta’O=-0.437, P< 0.001) and positively with Ayral’s score (beta’A=0.339, P< 0.01), especially accumulative Outerbridge’s score. Compared with other knee diseases, the hyaluronan level of OA knees was lower (P< 0.05). However, Ayral’s score and accumulative Outerbridge’s score were higher in OA knees (P< 0.001). The hyaluronan level in the synovial fluid of the knee can reflect the degree of synovitis and accumulative cartilage injury, especially synovitis. It reflects the degree of accumulative cartilage injury mainly when synovitis is more severe. The decrease of the hyaluronan level in the synovial fluid of OA knee is results of integrating effect of the synovitis and cartilage injury

Purpose of the study: The aim of this retrospective epidemiological study was to report the complete arthroscopic results concerning meniscus or cartilage injuries for procedures performed to repair the anterior cruciate ligament (ACL). The goal was to search for risk factors and improve patient care. Material and methods: Between 2000 and 2004, the same operator performed 129 consecutive ligamentoplasties to repair ACL tears. The following preoperative factors were analyzed: body weight, height, type and level of sports activity, laxity, positive pivot test, morphotype, time from accident to surgery. Meniscal lesions were identified and classified according to Trillat. The Beguin and Locker classification was used for cartilage lesions. The Panthéon-Sorbonne statistics laboratory performed the statistical analysis. Results: Meniscal lesions were found in 53.5% of knees and cartilage lesions in 24.2%. The medial meniscus was involved in 75.4% and the lateral meniscus in 20.3%, both in 4.3%. The injury could be repaired by suture or a conservative procedure for 45%. The medial compartment presented cartilage injury in 51.6% of knees, the patella in 29%, the trochlea in 19.35% and the same percentage for the lateral condyle. The degree of preoperative laxity, the time from accident to surgery and body mass index were statistically correlated with presence of a meniscal injury. Age, the degree of pre-operative laxity and body mass index were statistically correlated with presence of a cartilage injury. Discussion: Meniscal injuries are frequent in knees with ACL tears. The posterior segment of the medial ligament, which blocks anterior translation of the tibia if the ACL is absent, is predominantly involved. The amount of tibial movement below the femur and stress applied to the knee (particularly related to body mass) favor such lesions. Many lesions will heal spontaneously after surgery. Inversely others are more frequent after a longstanding tear. Cartilage injury is also frequent and occurs often on aging cartilage. The extent of tibial movements and their repetition as well as important stress are factors predictive of such injuries. Conclusion: Indications for reconstruction of the ACL in the young subject are well identified, less so in the older subject. This study confirms the usefulness of reconstructing the ACL to protect the menisci and joint cartilage. Excessive weight appears to be another important point to take into consideration for the surgical management of these patients

Aims: We studied by means of a magnetic resonance imaging (MRI) protocol, the junction area between supratrochlear (ST) surface and the femoral trochlear groove (FT). The variations of this junction area are they correlated with the patientñs functional signs and with the patellar cartilage injuries?Method: We practised on 87 patients (64 patellar instability, 23 patellar pains) and 25 witnesses, an MRI: DESS and MPR sequences. The trochlear bump was studied in the sagittal plan according to the aspect of the junction area and in measuring itñs height. Results: The junction area was dismembered in 4 types according to its slope with the ST surface: ÒßatÒ, ÒroundÒ, ÒobliqueÒ and ÒsquareÒ. No atÒ typeÒßwas found in cases of FT dysplasia. The ÒobliqueÒ and ÒsquareÒ types were more frequent in cases of important projection of the FT (p< 0.0001). These two types were more frequently associated with the patellar cartilage injuries (p< 0.08). The trochlear projection was maximum (p< 0.0001) in FT dysplasia with spur, with a maximum effect in this case on patellar instability (p< 0.01) and also on patellar pain (p< 0.05). Conclusion: The junction area between the ST surface and the FT groove was dismembered in 4 types. A þrst ßat type without trochlear bump, and 3 types deþning a trochlear Òstep of stairÒ, round, square and oblique in order of growing gravity. The latter two were more common when patellar cartilage injuries existed

Purpose: Removal of intra-articular foreign bodies (FB) constitues a major indication for elbow arthroscopy. The purpose of our study was to evalute our experience with arthroscopic treatment of elbow osteochondromatosis. Material and methods: Between September 1988 and June 2001 we performed elbow arthroscopy in 25 active patients (15 manual workers, 8 athletes including 2 high-level) who presented intra-articular FB osteochon-dromatosis of the elbow. Male gender predominated (n=22). Mean age at intervention was 42 years (17–68). The right (n=21) and dominant (n=24) side predominated. The mean clinical course before arthroscopy was two years. Seven patients had had upper limb trauma (five with elbow injury) a mean 60 months (6–144) before arthroscopy. Clinical assessment before arthroscopy and at last follow-up (mean follow-up 60 months, 8–138) included pain score (visual analogue scale), the notion of blocking and joint effusion and joint motion, as well as index of functional impairment during occupational and recreational activities and a subjective satisfaction index. Standard x-rays and arthroscan were obtained before arthroscopy to identify and evaluate intra-articular foreign bodies. Cartilage damage and presence of synovial anomalies were evaluated on the preoperative scan and during the intervention. Arthros-copy was performed according to the same procedure in all cases: lateral decubitus, arm cuff, anterior expoloration (anteromedial and anterolateral access). Standard x-rays were also obtained after arthroscopy and at last follow-up. Results: FB were found and extracted in all cases. Cartilage injury was associated in 14 cases. Synovectomy was performed systematically in case of synovitis, a macroscopic synovial anomaly, or to extract a FB trapped in the synovial (n=18). Osteophytes were shaved in 12 cases. The post-arthroscopic period was uneventful with no complications (vascular, nervous, infectious). Clinical improvement was significant and sustained and the occupational and recreational function indexes improved. The subjective satisfaction index remained high five years after arthroscopy. We did not have any clinical recurence (blockage) or radiographically detectable anomaly at last follow-up. Less favourable results (persistent pain) were obtained in patients who had cartilage injury. Discussion: Arthroscopy appears to be a safe treatment with long-term efficacy for osteochondromatosis of the elbow. Long-term prognosis is influenced most by presence of cartilage injury

Familial osteochondritis dissecans (FOCD) is an inherited defect of cartilage and bone characterized by development of large cartilage lesions in multiple joints, short stature and early onset osteoarthritis. We have studied a family from Northern Sweden with FOCD over five generations. All affected family members have a heterozygous missense mutation on exon 17 of the aggrecan gene, resulting in a Val-Met amino acid replacement in the G3 aggrecan C-type lectin domain (CLD). Aggrecan, a major proteoglycan of articular cartilage produced by chondrocytes, has a large protein core richly substituted with sulfated glycosaminoglycan chains. The unique structure, its high concentration within the cartilage extracellular matrix and its ability to form a supermolecular complex with hyaluronan and bind to other matrix proteins all profoundly influence the biomechanical properties of the tissue. Deletion of CLD in a chick aggrecan construct was found to influence its secretion from chondrocytes and human aggrecan constructs carrying the V2303M mutation showed diminished interactions with the ECM proteins tenascin-R, fibulin-1 and fibulin-2. To investigate the pathogenesis of FOCD, we studied chondrogenic differentiation of patient bone marrow mesenchymal stem cells and induced pluripotent stem cells. We demonstrated that the mutation results in accumulation of unfolded or misfolded aggrecan within the lumen of the chondrocyte endoplasmic reticulum. Associated with this is the failure to assemble a normal extracellular matrix. This explains the susceptibility of these patients to cartilage injury and the degenerative changes that lead to early onset osteoarthritis

Aims

The aim of this study was to evaluate the association between chondral injury and interval from anterior cruciate ligament (ACL) tear to surgical reconstruction (ACLr).

One of the core tenets of our philosophy for tissue regeneration include the use of “raw materials,” where biomaterials themselves serve as both building blocks and bioactive signals. In recent years, a few groups around the world have gravitated toward cartilage matrix as a potentially chondroinductive material for cartilage regeneration. The major challenge to date in cartilage injury has been creating a biomaterial-only strategy that is capable of regenerating true hyaline-like cartilage without the addition of growth factors or exogenous cells. In the past few years, we have focused our efforts on establishing chondroinductivity in vitro, and in developing new materials synthesis strategies to provide ease of application for orthopedic surgeons in the operating room. By leveraging nanotechnology, we have developed a paste-like material constructed from cartilage matrix with encouraging mechanical performance post-crosslinking, and which avoids contraction after extended time. Looking to the future, we are working on next-generation approaches to chondroinductive materials. We have encouraging preliminary data which suggest the possibility of a chondroinductive response to a novel peptide sequence in vitro, which may be enhanced by simultaneous inclusion of adhesion peptides. Initial in vivo data in regeneration of rabbit femoral condyle cartilage defects may suggest promising regenerative capabilities with hydrogels based on these peptides. If indeed chondroinductive materials exist, and if they can be delivered easily, are safe, and can be provided at reasonable cost and with a reasonable regulatory strategy, chondroinductive materials may hold the potential to revolutionize cartilage regeneration

Aims

This systematic review aimed to summarize the full range of complications reported following ankle arthroscopy and the frequency at which they occur.

Aims

Orthopaedic surgery requires grafts with sufficient mechanical strength. For this purpose, decellularized tissue is an available option that lacks the complications of autologous tissue. However, it is not widely used in orthopaedic surgeries. This study investigated clinical trials of the use of decellularized tissue grafts in orthopaedic surgery.

Aims

The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach.

The February 2024 Knee Roundup³⁶⁰ looks at: Do patients with hypoallergenic total knee arthroplasty implants for metal allergy do worse? An analysis of healthcare utilizations and patient-reported outcome measures; Defining a successful total knee arthroplasty; Incidence, microbiological studies, and factors associated with periprosthetic joint infection after total knee arthroplasty; A modified Delphi consensus statement on patellar instability; Cause for concern? Significant cement coverage in retrieved metaphyseal cones after revision total knee arthroplasty; Prevalence of post-traumatic osteoarthritis after anterior cruciate ligament injury remains high despite advances in surgical techniques; Cost-effectiveness of arthroscopic partial meniscectomy versus physical therapy for traumatic meniscal tears in patients aged under 45 years.

Introduction. NF-κB transcription factors regulate a number of genes that are activated under stress conditions. Blockage of the the canonical NF-κB pathway has been emerged as a possible strategy to cure osteoarthritis and rheumatoid arthritis. However, the roles of κNF-B in normal skeletal physiology are largely unknown owing to the lack of suitable animal models. Here, we investigated the function of canonical κNF-B pathway in the cartilaginous skeleton by ablating Nemo (NF-κB essential modulator) in chondrocytes using the Col2a1 transgene. Methods. Mice were analyzed by skeletal staining, histology, proliferation and apoptosis assays at various stages. Histochemistry, GAG assay and immunohistochemistry were utilized to assess the impact of NEMO-deficiency in cytokine-induced cartilage degradation of hip explants. To identify genes regulated through the canonical NF-κB pathway in response to injury, an ex vivo hip avulsion model was applied. 24 genes known to be induced early following cartilage injury were assessed in wildtype and mutant hips by RT-PCR. Time lapse photography was used to investigate chondrocyte migration in vitro. Atomic force microscopy (AFM) was applied to assess biomechanical properties of the cartilage. Pathological changes of articular cartilage were scored in aged joints. Results. Mutant mice exhibited moderate dwarfism postnatally characterized by disorganized growth plate, abnormal chondrocyte proliferation, apoptosis and migration. AFM indentation experiments showed no changes in biomechanical properties of the mutant growth plate compared with control. Exposure of aggrecan degradation neoepitopes and release of GAGs were less pronounced in mutant hip explants stimulated by cytokines. Of the 24 genes regulated 4h following injury in wildtype hips, only Arginase-1 was suppressed in the mutant hips, while the expression levels of most other inflammatory response genes e.g. TSG-6, NOS2, COX2, IL6 and IL1b were unaffected. A small number of genes, IL-18, MMP-3 and Has-2 were further upregulated upon injury in Nemo-deficient compared with wildtype hips. Aging mutant mice showed signs of osteoarthritis comparable to wildtype. Conclusion. Nemo-deficient mice have demonstrated an important role for canonical NF-κB signaling in skeletal growth by modulating chondrocyte behavior. Even though the catabolic effects of pro-inflammatory cytokines in cartilage could be partially eased by blocking the canonical NF-κB pathway, canonical NF-κB signaling seems to play only a minor role in injury-induced inflammatory gene expression and the development of spontaneous OA

The February 2023 Foot & Ankle Roundup³⁶⁰ looks at: Joint inflammatory response in ankle and pilon fractures; Tibiotalocalcaneal fusion with a custom cage; Topical application of tranexamic acid can reduce blood loss in calcaneal fractures; Risk factors for failure of total ankle arthroplasty; Pain catastrophizing: the same as pain forecasting?.

Background. Osteoarthritis (OA), a common degenerative disorder of synovial joints, is characterized by disruption of the extracellular matrix (ECM) homeostasis with an overall misbalance towards cartilage catabolism. Integrins are alpha/beta heterodimeric transmembrane proteins transmitting chemical and biomechanical signals into the cells. There is a growing consensus that changes of ECM composition by proteolytic degradation of matrix constituents, or alteration of the biomechanical microenvironment of chondrocytes caused by chronic stress or injury significantly increase the risk of OA through the perturbation of integrin signaling. In order to further investigate the role of the b1 integrin subfamily in OA, we have challenged hip cartilage explants dissected for mice lacking beta1 integrins in chondrocytes by cytokines, ECM degradation products or mechanical stimulation. Methods. Femoral articular cartilages were avulsed from hip joints of 6 weeks old wild type (WT) and b1fl/fl-PrxCre mutant (MT) mice. For the chemically-induced OA-like stimulation, femoral caps were cultured for 3 days in serum-free DMEM/F12 with or without the supplementation of interleukin-1a (IL1a), 120kDa cell-binding fibronectin fragments (120FNf), or tumor necrosis factor-alpha (TNFa) + oncostatin M (OM). Sulphated glycosaminoglycan (sGAG) release of the explants were measured in the supernatants by the 1,9-dimethylmethlene blue (DMMB) assay. Proteoglycan loss was monitored by Safranin-O (SO) staining on cryo-sections of the explants. For the cartilage injury model, avulsed femoral caps were either directly snap-frozen or kept in serum-free DMEM/F12 for 4 hours before snap-freezing. Gene expression changes were analyzed by quantitative RT-PCR using a pre-determined set of genes regulated by injury. Results. Articular cartilages of MT mice were found to have consistently higher release of GAGs when exposed to cytokines or 120FNf. IL-1a exerted the highest catabolic stimulation. The ex vivo biochemical analysis was further verified by SO staining demonstrating more pronounced proteoglycan loss on MT sections compared to WT. Assessing the mRNA of articular cartilages subjected to the injury model, revealed expression changes in genes which have been previously implicated in OA: Il1a (interleukin 1, alpha) and Ptgs2 (prostaglandin-endoperoxide synthase 2) were upregulated in MT mice; whereas Il1rl1 (interleukin 1 receptor-like 1) and Nos2 (nitric oxide synthase 2) expression levels were significantly reduced in MT compared to WT. Conclusion. The data imply that b1 integrins play a protective role against cytokine- and fibronectin fragment-induced cartilage degradation. Our findings also suggest that b1 integrins modulate the expression of catabolic factors upon mechanical insults

Aims

To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults.

Aims

Hip arthroscopy has gained prominence as a primary surgical intervention for symptomatic femoroacetabular impingement (FAI). This study aimed to identify radiological features, and their combinations, that predict the outcome of hip arthroscopy for FAI.

Aims

Pellino1 (Peli1) has been reported to regulate various inflammatory diseases. This study aims to explore the role of Peli1 in the occurrence and development of osteoarthritis (OA), so as to find new targets for the treatment of OA.

Aims

To assess the alterations in cell-specific DNA methylation associated with chondroitin sulphate response using peripheral blood collected from Kashin-Beck disease (KBD) patients before initiation of chondroitin sulphate treatment.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by progressive cartilage degradation, synovial membrane inflammation, osteophyte formation, and subchondral bone sclerosis. Pathological changes in cartilage and subchondral bone are the main processes in OA. In recent decades, many studies have demonstrated that activin-like kinase 3 (ALK3), a bone morphogenetic protein receptor, is essential for cartilage formation, osteogenesis, and postnatal skeletal development. Although the role of bone morphogenetic protein (BMP) signalling in articular cartilage and bone has been extensively studied, many new discoveries have been made in recent years around ALK3 targets in articular cartilage, subchondral bone, and the interaction between the two, broadening the original knowledge of the relationship between ALK3 and OA. In this review, we focus on the roles of ALK3 in OA, including cartilage and subchondral bone and related cells. It may be helpful to seek more efficient drugs or treatments for OA based on ALK3 signalling in future.

Aims

Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism.

Osteoarthritis (OA) affects bone cartilage and underlying bone. Mechanically, the underlying bone provides support to the healthy growth of the overlying cartilage. However, with the progress of OA, bone losses and cysts occur in the bone and these would alter the biomechanical behaviour of the joint, and further leading to bone remodelling adversely affect the overlying cartilage. Human femoral head and femoral condyle were collected during hip or knee replacement operation due to the end stage of osteoarthritis (age 50–70), and the cartilage patches were graded and marked. A volunteer patient, with minor cartilage injury in his left knee while the right knee is intact, was used as control. Peripheral quantitative computed tomography (pQCT) was used to scan the bone and to determine the volumetric bone mineral density (vBMD) distribution. The examination of retrieved tissue explants from osteoarthritic patients revealed that patches of cartilage were worn away from the articular surface, and patches of intact cartilage were left. The cysts, ranging from 1 to 10mm were existed in all osteoarthritic bones, and were located close to cartilage defects in the weight-bearing regions, and closely associated with the grade of cartilage defect as measured by pQCT. The bone mineral density (vBMD) distribution demonstrated that the bones around cysts had much higher vBMD than the trabecular bone away from the cysts. Compared to the subchondral bone under thicker cartilage, subchondral bone within cartilage defect has higher vBMD. This may result from the mechanical stimulation as a result of bone-bone direct contact with less protection of cartilage in cartilage defect regions. This study showed an association between cartilage defect and subchondral bone mineral density distribution. Cysts were observed in all osteoarthritic samples and they are located close to cartilage defects in the weight-bearing regions. Cartilage defect altered the loading pattern of the joints, this leading to the bone remodelling and resultant bone structural changes as compared to the normal bone tissues. This work was financially supported by The ARUK Proof of Concept Award (grant no: 21160)

The internal fixation of osteochondral fragments in fractures normally utilizes intra-articular screws inserted through a pilot hole drilled into cartilage/bone. This trauma causes cartilage injury leading to chondrocyte death. We have quantified the cell death following cartilage drilling and identified irrigation conditions that can protect chondrocytes. Articular cartilage of bovine metacarpophalangeal joints of 3yr-old cows was irrigated in the presence/absence of saline of various compositions. Holes were then made using a standard 1.5mm drill (Ortho Solutions Ltd.) at 18,000 rpm through the articular cartilage into bone. Osteochondral explants were then harvested and cultured in Dulbecco's Modified Eagle's Medium containing chloromethylfluorescein-di-acetate and propidium iodide (10uM each), to label living chondrocytes green and dead cells red, respectively. Axial images were taken by confocal microscopy and the width of the zone of cell death (ZCD) around the hole determined. With no irrigation, new drills caused a ZCD of 171±25um, which was increased when drills used 50+ times were tested (279±31um;p=0.03). With saline irrigation, the ZCD was reduced for old drills (150±6um;p=0.016) but not for new drills (124±8um) suggesting the heating effect of the old drills caused additional chondrocyte death. However for new drills, the ZCD was further reduced significantly to 82±7um when the osmolarity of the saline irrigation solution was raised to 480mOsm using sucrose. Data are mean±s.e.m., from at least 5 separate experiments each with a minimum of 3 replicates. The results demonstrate a chondroprotective effect of raising the osmolarity of saline used during drilling of cartilage which could be clinically beneficial

1. The semilunar cartilages are part of the rotator mechanism of the knee joint. 2. Movement of the weight-bearing knee comprises synchronous lateral rotation of the tibia with extension and medial rotation of the tibia with flexion. 3. When this synchrony is disturbed, injuries to the semilunar cartilages result. 4. Damage to the anterior two-thirds of the medial cartilage blocks lateral rotation of the tibia, with consequent physical signs that are pathognomonic of the retracted and the bowstring cartilage, which are the most common types of injury. 5. Each type of cartilage injury produces its own pattern of erosion of articular cartilage and its own sequence of symptoms as so-called arthritis develops. 6. The sequence of symptoms may be halted and often reversed by removal of the torn cartilage. Operation is warranted in most cases however long the history and whatever the age of the patient. 7. The development of medial retropatellar arthritis is explained. The symptoms are often relieved by removal of the medial semilunar cartilage and adequate post-operative rehabilitation

Purpose: Chondral injuries of the knee are commonly seen at arthroscopy, yet there is no consensus on the most appropriate treatment method. However, untreated cartilage injury predisposes to osteoarthritis contributing to pain and disability. For cell-based cartilage repair strategies, an ex-vivo expansion phase is required to obtain sufficient numbers of cells needed for therapy. Although recent reports demonstrated the central role of oxygen for the function and differentiation of chondrocytes, little is known of the effect of physiological low oxygen concentrations during the expansion of the cells and whether this alters their chondrogenic capacity. Method: Initial studies of chondrocyte expansion were performed in mature mice, with cells expanded at either atmospheric oxygen tension (21%) or 5% 02 in monolayer cultures. Chondrogenic differentiation was subsequently assessed via micromass culture. Having determined that oxygen tension influences murine chondrocyte expansion and differentiation, similar studies were conducted using adult human chondrocytes taken from knee arthroplasty off-cuts, with mRNA expression of select genes involved in the chondrogenic program analyzed by q-PCR. Results: Cellular morphology was improved in hypoxic culture, with a markedly more fibroblastic appearance seen after greater than 2 passages in 21% O2. Micromass cultures maintained in hypoxic conditions demonstrated stronger staining with Alcian blue, indicating stronger expression of cartilaginous glycosaminoglycans. Collagen type II mRNA expression was two-fold higher in cells expanded at 5% as compared to expansion at 21% O2. Micromass cultures grown at 21% O2 showed up to a twofold increase in the tissue content of glycosaminoglycans when formed with cells expanded at 5% instead of 21% O2. However, no differences in the mRNA expression or staining for collagen type II protein were observed in these micromass cultures. Hypoxia (5% O2) applied during micromass cultures gave rise to tissues with low contents of glycosaminoglycans. Conclusion: In-vivo, chondrocytes are adapted to a hypoxic environment. Taking this into account, applying 5% O2 in the expansion phase in the course of cell-based cartilage repair strategies, may result in a repair tissue with higher quality by increasing the content of glycosaminoglycans

Purpose. The prevalence of focal chondral lesions reported inthe literature during knee arhroscopy can be as high as 63%. Of these, more than half are either grade III or grade IV lesions (Outerbridge). Full thickness cartilage lesions ranging from 2cm2 to 10cm2 are the most challenging to treat. To goal of this study was to evaluate clinical outcomes of pain, function and quality of life, along with radiological outcomes of cartilage repair using microfracture, autologous minced cartilage and polymeric scaffold. Method. A cohort of thirty-eight patients with Outerbridge grade III or IV cartilage injuries larger than 2cm2 in the knee's femoral condyle, trochlea or patella were prospectively folowed since 2008. They were all treated with microfracture, fresh minced autologous cartilage grafting and a polymeric scaffold technique through mini-arthrotomy of the knee. Autografts and scaffolds were secured to subchondral bone using fibrin glue and tran-sosseous resorbable sutures. Patients were evaluated pre and postoperatively using VAS scores for pain, WOMAC and IKDC scores for knee function and SF-36 questionnaire for quality of life. Clinical evaluations were done by physical examination, and imaging was done using X-Rays, MRI and arthro-CT. Results. Mean follow-up time was14.64.6 months. Mean age was 48.39.3 years old. Pre-op lesions averaged 3.51.5 cm2. VAS pain scores were significantly reduced after surgery (7,62 to 2,52.3, p<. 0001). Improvement in knee function using IKDC score improved from 26,717.5 to 55,415.3, p<. 001). In addition, WOMAC total scores showed significant reduction from 55,520.3 to 27,517.6. SF-36 quality of life Physical Component Summary improved from 26,411.4 to 45,812.3, p<. 01; Mental Component Summary improved from 41,916.8 to 49,411.2, p<. 048). Imaging results indicate sustained cartilage thickness from 6 to 18 months. One patient was an early failure due to scaffold loosening, and two patients had no clinical improvement and no significant cartilage regeneration on MRI and Arthro-CT imaging at 6 months post-op. Conclusion. The combination of microfractures, fresh minced autologous cartilage grafting and polymeric scaffold fixation seems to be an effective treatment option for post-traumatic and focal cartilage lesions of the knee in the short term. A longer-term follow-up to evaluate the sustainability of these results is ongoing. Shortcomings of this study are its short term, the lack of second look arthroscopies and cartilage biopsies to evaluate cartilage microstructure, and the absence of a gold standard treatment for full-thickness cartilage lesions larger than 2cm2 that could be used as a control

Purpose of the study: Revision ligamentoplasty can improve function and laxity control but with a less satisfactory result than obtained after primary reconstruction. The purpose of this study was to report management practices and results of revision ACL reconstructions and to assess the course of meniscocartilage damage and determine causes of failures. Material and method: This was a consecutive series of ten patients, mean age 30 years (range 17–48) who underwent arthroscopic reconstruction. The review was retrospective. Criteria for failure were redevelopment of instability and/or pain, objective laxity, and a KT-100 differential greater than 5 mm. The IKDC protocol was used for the clinical and radiographic assessment. Goniometry, arthroscan and MRI were also performed. The position of the tunnels was analysed according to the Aglietti criteria. The type of surgery, transplant used and status of the menisci and cartilage were analysed. Results: Mean follow-up of the second revision was 38 months. At last follow-up, seven patients had a global IKDC score of A or B. Two patients had resumed regular sports activities at the same level as before the first tear, four at a lower level. Four had interrupted their sports activities. At the second revision, two patients exhibited medial femorotibial narrowing measured at less than 50%, three had a remodelled medial femorotibial compartment and one a remodelled lateral compartment. All had a partial homolateral meniscectomy and seven had cartilage injuries (3 ICRS III and 1 ICRS IV). At the successive interventions, the number of meniscal lesions, meniscetomies, and cartilage lesions increased (p=0.016, 00098 and 0.0197 respectively). ICRS grade II and IV cartilage lesions were associated with an overall C or D IKCD (p=0.0472). The cartilage lesions were more frequent in knees with meniscal lesions and meniscectomies. The causes of failure of the primary ligamentoplasty and of the first revision (six and seven patients respectively) were poor position of the tunnels (respectively 4 and 1 patients). Discussion: In 70% of the patients outcome after repeated revision was good or excellent, although the quality declined with increasing number of revisions, in relation to the development of meniscal and cartilaginous lesions. These latter were more frequent and more severe, related to recurrent laxity. Failures were mainly due to recurrent trauma followed by technical errors

Introduction. Osteoarthritis (OA) is a slow progressive disease and a huge economic burden. A new target for therapy could be a growth factor treatment to prevent the loss of cartilage following injuries to the joint. BMP-7 is a promising candidate for such a novel therapy based on growth factors. In this study we combined the chondroprotective effects of BMP-7 with a novel thermosensitive hydrogel to prevent cartilage degeneration in a murine OA model. M&M. A BDI based thermosensitive hydrogel (Pluronic 123 with Butandiisyocyanate (BDI); LivImplant GmbH, Germany) was augmented with BMP-7 (rh-BMP-7, Olympus Biotech, France; 0.2 µg BMP-7/10µg Hydroge). To investigate the effects on OA progression we used the murine DMM (Destabilization of the medial meniscus) model for OA induction. Animal testing was approved by the Government Commitee of Upper Bavaria (file reference: 55.2-1-54-2532-150-13). A total of 38 C57BL/6 mice were included in this study. Immediately after the DMM surgery and wound closure BMP-7 mixed with BDI Hydrogel or only the BDI Hydrogel was administered via intraarticular injection. The following groups were examined: A) BMP-7 augmented BDI hydrogel B) only BDI hydrogel C) no injection following surgery D) control, healthy contralateral knee joint. After 4 (n=4 per group) and 8 (n=8) weeks mice were euthanized and knees were compared histologically. Results/Discussion. After 4 weeks the BMP-7 treated group showed a significant lower cartilage erosion compared to the group which only received DMM surgery. In the BMP-7 treated knee, osteoarthritis progression was also milder after 8 weeks than in knees of the DMM group. In all knees, except the control group, cartilage degeneration further progressed throughout the observation period. The contralateral joints showed no severe OA. We did not observe any inflammation or systemic reaction to the hydrogel. Taken together, we can conclude that BMP-7 showed a positive effect on the cartilage structure. Yet, the effect of a single administration is not strong enough to see a significant effect after 8 weeks. Furthermore, we can conclude, that the intraarticular administration of a thermosensitive hydrogel is an easy and feasible way to administer active agents precise to the joint

Introduction: Chondral injuries of the knee are commonly seen at arthroscopy, yet there is no consensus on the most appropriate treatment method. However, untreated cartilage injury predisposes to osteoarthritis contributing to pain and disability. For cell-based cartilage repair strategies, an ex vivo expansion phase is required to obtain sufficient cells for therapeutic intervention. Although recent reports demonstrated the central role of oxygen in the function and differentiation of chondrocytes, little is known of the effect of physiological low oxygen concentrations during the expansion of the cells and whether this alters their chondrogenic capacity. Methods: Articular mouse chondrocytes were prepared from the distal femoral condyles of adult mice and chondrocytes were liberated by collagenase type II treatment. Cells were cultured in RPMI 1640 media in monolayer under normoxic or hypoxic conditions (5% O2). Chondrogenic potential was subsequently assessed by plating the cells under micromass conditions and glycosaminoglycan deposition was determined by alcian blue staining. Having determined that oxygen tension infiuences murine chondrocyte expansion and differentiation, similar studies were conducted using adult human chondrocytes taken from knee arthroplasty off-cuts, and Aggrecan (ACAN) gene expression was analyzed using real-time quantitative PCR. Results: Cellular morphology of cells from mouse articular cartilage was improved in hypoxic culture, with a markedly more fibroblastic appearance seen after greater than 2 passages in normoxic conditions. Micromass cultures maintained in hypoxic conditions demonstrated stronger staining with alcian blue, indicating stronger expression of cartilage-associated glycosaminoglycans. Expansions of human chondrocytes under hypoxic conditions led to an ~ 2-fold increase in the expression of ACAN in comparison to cells in normoxic conditions. Differentiation of passage 2 chondrocytes under hypoxic conditions also improved the expression of ACAN when compared to culturing under normoxia. Ten day hypoxic cultures exhibited an ~ 5-fold increase in ACAN expression in comparison to normoxic cultures. Interestingly, ACAN expression normoxic-cultured cells could be increased by > 4-fold by transfer to hypoxic conditions. Conclusions: In vivo, the chondrocytes are adapted to an avascular hypoxic environment. Accordingly, applying 5% O2 in the expansion phase in the course of cell-based cartilage repair strategies may more closely mimic the normal chondrocyte microenvironment and may result in a repair tissue with higher quality by increasing the content of glycosaminoglycans

Objectives: Hyaluronic acid (HA) is used in osteoarthritis especially for the control of pain. In this animal study, we investigated the effects of HA on the early stage of osteoarthritis. Methods: The experimental osteoarthritis model was constituted on 10 rabbits by the way of anterior cruciate ligament transection. In HA group, HA was injected 0.6 ml (15mg/ml) dosage per week for 3 weeks in right knees of ten rabbits and in SF group, saline was injected 0.6 ml dosage per week for 3 weeks in left knees of rabbits. Because three rabbits died in experimental period, fourteen knees of seven rabbits were taken into account for the study. The knees of rabbits, which were sacrified at 12th weeks after index operation, were measured according to cartilage area and Mankin scale. Results: The mean cartilage area of HA and SF groups were measured 1.097 mm2 and 0.477 mm2, respectively. The difference of mean cartilage area between HA and SF groups was statistically significant (p< 0.05). According to Mankin scale, the mean total point of scale was measured 3.57 in HA group and 11.14 in SF group and the difference between mean total points of groups was significant (p< 0.05). Although, there is no significant difference in cellular abnormality, matrix staining, and tidemark continuity criteries of scale, we found the significant difference between total point and structure of cartilage criteria of scale. Conclusions: HA has a retarder effect on progression of cartilage injury in early stage osteoarthritis