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

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. Magnesium ions (Mg. 2+. ) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg. 2+. combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg. 2+. in cartilage repair. Methods. A total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg. 2+. treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg. 2+. was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results. The histological results showed that the 0.5 mol/L Mg. 2+. group had deeper positive staining in haematoxylin-eosin (H&E), safranin O, Alcian blue, and type II collagen staining. The new cartilage coverage in the injury area was more complete, and the regeneration of hyaline cartilage was higher. The RT-qPCR results showed that sirtuin 1/bone morphogenetic protein-2/sex-determining region Y box 9 (SIRT1/BMP-2/SOX-9) and hypoxia-inducible factor 1-alpha (HIF-1α) messenger RNA levels were up-regulated after Mg. 2+. injection. Conclusion. MFX combined with Mg. 2+. treatment has a positive effect on cartilage repair. The Mg. 2+. injection dose of 0.5 mol/L is most effective in enhancing microfracture-mediated cartilage repair. Cite this article: Bone Joint Res 2025;14(1):20–32

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

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

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

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. 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. 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

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

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

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