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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 86 - 86
2 Jan 2024
Feng M Dai S Ni J Mao G Dang X Shi Z
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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


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 730 - 735
1 May 2005
Sharpe JR Ahmed SU Fleetcroft JP Martin R

In this study a combination of autologous chondrocyte implantation (ACI) and the osteochondral autograft transfer system (OATS) was used and evaluated as a treatment option for the repair of large areas of degenerative articular cartilage. We present the results at three years post-operatively. Osteochondral cores were used to restore the contour of articular cartilage in 13 patients with large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n = 7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath a periosteal patch covering the cores. After one year, the patients had a significant improvement in their symptoms and after three years this level of improvement was maintained in ten of the 13 patients. Arthroscopic examination revealed that the osteochondral cores became well integrated with the surrounding cartilage. We conclude that the hybrid ACI/OATS technique provides a promising surgical approach for the treatment of patients with large degenerative osteochondral defects


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 86 - 86
1 Apr 2017
Jordan R Saithna A
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Background. Despite arthroscopy being the gold standard for long head of biceps pathology, the literature is seemingly lacking in any critical appraisal or validation to support its use. The aim of this study was to evaluate its appropriateness as a benchmark for diagnosis. The objectives were to evaluate whether the length of the tendon examined at arthroscopy allows visualisation of areas of predilection of pathology and also to determine the rates of missed diagnoses when compared to an open approach. Methods. A systematic review of cadaveric and clinical studies was performed. The search strategy was applied to Medline, PubMed and Google Scholar databases. All relevant articles were included. Critical appraisal of clinical studies was performed using a validated quality assessment scale. Results. Six articles were identified for inclusion in the review. This included both clinical and cadaveric studies. The overall population comprised 25 cadaveric specimens and 575 patients. Cadaveric studies showed that the use of a hook probe allowed arthroscopic visualisation of between 28% and 48% of the overall length of the LHB. In the clinical series the rate of missed diagnoses at arthroscopy when compared to open exploration ranged between 33% and 49%. Conclusions. The standard technique of pulling the LHB tendon into the joint at glenohumeral arthroscopy provides only limited excursion and does not allow visualisation of areas of predilection of pathology. This is confirmed by an extremely high rate of missed diagnoses when comparing arthroscopy to open exploration. It is important that clinicians recognise that a “normal” arthroscopic examination of the LHB tendon does not exclude pathology and that published literature reporting sensitivities and specificities for physical examination and imaging tests based on arthroscopy as a gold standard are invalid. Level of evidence. IIa – systematic review of cohort studies. Conflict of Interests. The authors confirm that they have no relevant financial disclosures or conflicts of interest. Ethical approval was not sought as this was a systematic review


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_1 | Pages 18 - 18
1 Jan 2017
Wu J Zhou Z Zhao X Xue W Xu J Kirk T
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The health of a synovial joint is relied on normal function and coordination of a group of tissues such as articular cartilage (AC), ligaments, tendons and muscles. Osteoarthritis (OA), which is the most common joint disease, is clinically characterised by lesion of AC. Despite this, injury of a ligament or tendon or muscle generates a joint instability, which accelerates deterioration of AC and progression of OA. Traditional histology is often used to study the pathology of biological tissues. It requires tissue biopsy, which traumatises the donor tissues. Therefore, it is not an idea method for assessing AC, ligaments and tendons as the tissues have a poor healing capability. There is a worldwide demand of an imaging technique that diagnoses the microstructural changes of chondral and connective tissues without biopsy. Confocal arthroscopy (Optiscan Pty Ltd, Australia) possesses a Ø 6.3 mm probe and offers a 0.7 µm lateral imaging resolution and 7 µm axial resolution. It has been successfully used for examining the internal microstructural disorders in rotator cuff tendons of human cadavers without tissue biopsy (WU et al., 2015). This study investigates the capability of confocal arthroscopy as optical histology for assessing the internal microstructure of AC, ligaments, tendons and muscles in a knee joint. Four sheep keen joints were freshly donated by other research unrelated to this study. After 5 ml clinical grade fluorescein solution at 0.05 g/L was injected into the joint cavity of a knee joint, the joint was passively exercising for about 10 minutes. The joint was then open collaterally and washed thoroughly using PBS for acquiring the microstructure of AC, ligaments, tendons and muscles using the confocal arthroscopy. Results: without biopsy, confocal arthroscopy offers an imaging resolution for onsite distinguishing the subtle microstructural difference of AC in the weight-bearing and non-weight bearing region. It also permitted visualising the hierarchical collagen structure in ligaments and tendons at a fibre level, and characterising the muscle nuclei, motor-neurons, moto-neuron synapse and striates of myofibres. Confocal arthroscopy showed the early promise to act as optical histology for studying the microstructure of chondral and a range of connective tissues, which allows understand better the health status of a knee joint. Since a sheep knee joint is very small for operating a normal procedure of an arthroscopic examination, an open knee joint surgery was performed in this study to allow imaging the microstructure of AC and a range of connective tissues. This is accounted as a limitation in the study. Nevertheless, this study demonstrated the development of confocal arthroscopy may lead to optical histology of the internal microstructure of AC and a group of connective tissues, which offers understanding more comprehensively the healthy status of a knee joint


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVI | Pages 40 - 40
1 Aug 2012
Dhinsa B Nawaz S Gallagher K Carrington R Briggs T Skinner J Bentley G
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Introduction. Autologous chondrocyte implantation (ACI) is contra-indicated in a joint rendered unstable by a ruptured anterior cruciate ligament (ACL). We present our experience of ACI repair with ACL reconstruction. Methods. Patients underwent arthroscopic examination and cartilage harvesting of the knee. A second operation was undertaken approximately six weeks later to repair the ruptured ACL with hamstring graft or Bone patella-Bone (BPB) and to implant the chondrocytes via formal arthrotomy. Three groups were assessed: Group 1: Simultaneous ACL Reconstruction and ACI; Group 2: Previous ACL Reconstruction with subsequent ACI repair; Group 3: Previously proven partial or complete ACL rupture, deemed stable and not treated with reconstruction with ACI procedure subsequently. Patients then underwent a graduated rehabilitation program and were reviewed using three functional measurements: Bentley functional scale, the modified Cincinnati rating system, and pain measured on a visual analogue scale. All patients also underwent formal clinical examination at review. Results. Those who underwent simultaneous ACL Reconstruction and ACI had a 47% improvement in Bentley functional scale, 36% improvement in visual analogue score and 38% improvement in the modified Cincinnati rating system. This is in contrast to only a 15% improvement in the modified Cincinnati rating system, 30% improvement in Bentley functional scale, and 32% improvement in visual analogue score in patients who had ACI repair after previous ACL reconstruction. 68% of patients who had the procedures simultaneously rated their outcome as excellent/good and 27% felt it was a failure. In contrast 38% of patients rated their outcome as a failure if they had ACI repair without reconstruction of ACL rupture. Conclusion. Symptomatic cartilage defects and ACL deficiency may co-exist in many patients and represent a treatment challenge. Our results suggest that a combined ACL and ACI repair is a viable option in this group of patients and should reduce the anaesthetic and operative risks of a two-stage repair. Patients with complete rupture of ACL despite being deemed stable performed poorly at review and our study suggests all complete ruptures regardless of stability should be treated with a reconstruction when performing an autologous chondrocyte implantation


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 3 | Pages 417 - 424
1 Mar 2009
Millar NL Wei AQ Molloy TJ Bonar F Murrell GAC

The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry.

We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008).

These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.