The aim of this study was to assess the effect
of injecting genetically engineered chondrocytes expressing transforming
growth factor beta 1 (TGF-β1) into the knees of patients with osteoarthritis.
We assessed the resultant function, pain and quality of life. . A total of 54 patients (20 men, 34 women) who had a mean age
of 58 years (50 to 66) were blinded and randomised (1:1) to receive
a single injection of the active treatment or a placebo. We assessed
post-treatment function, pain severity, physical function, quality
of life and the incidence of treatment-associated adverse events. Patients
were followed at four, 12 and 24 weeks after injection. At final follow-up the treatment group had a significantly greater
improvement in the mean International Knee Documentation Committee
score than the placebo group (16 points; -18 to 49, vs 8
points; -4 to 37, respectively; p = 0.03). The treatment group also
had a significantly improved mean visual analogue score at final
follow-up (-25; -85 to 34, vs -11 points; -51 to
25, respectively; p = 0.032). Both cohorts showed an improvement
in Western Ontario and McMaster Osteoarthritis Index and Knee Injury
and Osteoarthritis Outcome Scores, but these differences were not statistically
significant. One patient had an anaphylactic reaction to the preservation
medium, but recovered within 24 hours. All other adverse events
were localised and resolved without further action. . This technique may result in improved clinical outcomes, with
the aim of slowing the degenerative process, leading to improvements
in pain and function. However, imaging and direct observational
studies are needed to verify
Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like
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. A total of 12 patients (12 knees) with symptomatic, post-traumatic, full-thickness cartilage lesions (1.0 to 4.0 cm2) 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.Aims
Methods
This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology. Initial research questions were generated using an online survey sent to all 680 members of the British Association for Surgery of the Knee (BASK). Duplicates were removed and a longlist was generated from this scoping exercise by a panel of 13 experts from across the UK who provided oversight of the process. A modified Delphi process was used to refine the questions and determine a final list. To rank the final list of questions, each question was scored between one (low importance) and ten (high importance) in order to produce the final list.Aims
Methods
The aim of this study was to evaluate whether achieving medial joint opening, as measured by the change in the joint line convergence angle (∆JLCA), is a better predictor of clinical outcomes after high tibial osteotomy (HTO) compared with the mechanical axis deviation, and to find individualized targets for the redistribution of load that reflect bony alignment, joint laxity, and surgical technique. This retrospective study analyzed 121 knees in 101 patients. Patient-reported outcome measures (PROMs) were collected preoperatively and one year postoperatively, and were analyzed according to the surgical technique (opening or closing wedge), postoperative mechanical axis deviation (deviations above and below 10% from the target), and achievement of medial joint opening (∆JLCA > 1°). Radiological parameters, including JLCA, mechanical axis deviation, and the difference in JLCA between preoperative standing and supine radiographs (JLCAPD), an indicator of medial soft-tissue laxity, were measured. Cut-off points for parameters related to achieving medial joint opening were calculated from receiver operating characteristic (ROC) curves.Aims
Methods
The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI). This single-centre study focused on a cohort of 24 patients with cam- or pincer-type FAI, full-thickness femoral or acetabular chondral lesions, or osteochondral lesions ≥ 2 cm2, who underwent surgical hip dislocation for FAI correction in combination with AMIC between March 2009 and February 2016. Baseline data were retrospectively obtained from patient files. Mid-term outcomes were prospectively collected at a follow-up in 2020: cartilage repair tissue quality was evaluated by MRI using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score. Patient-reported outcome measures (PROMs) included the Oxford Hip Score (OHS) and Core Outcome Measure Index (COMI). Clinical examination included range of motion, impingement tests, and pain.Aims
Methods
To determine the relationship between articular cartilage status and clinical outcomes after medial opening-wedge high tibial osteotomy (MOHTO) for medial compartmental knee osteoarthritis at intermediate follow-up. We reviewed 155 patients (155 knees) who underwent MOHTO from January 2008 to December 2016 followed by second-look arthroscopy with a mean 5.3-year follow-up (2.0 to 11.7). Arthroscopic findings were assessed according to the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. Patients were divided into two groups based on the presence of normal or nearly normal quality cartilage in the medial femoral condyle: good (second-look arthroscopic) status (ICRS grade I or II; n = 70), and poor (second-look arthroscopic) status (ICRS grade III or IV; n = 85) groups at the time of second-look arthroscopy. Clinical outcomes were assessed using the International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 36-Item Short Form survey.Aims
Methods
Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections.Aims
Methods
Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies.
When transferring tissue regenerative strategies
involving skeletal stem cells to human application, consideration needs
to be given to factors that may affect the function of the cells
that are transferred. Local anaesthetics are frequently used during
surgical procedures, either administered directly into the operative
site or infiltrated subcutaneously around the wound. The aim of
this study was to investigate the effects of commonly used local anaesthetics
on the morphology, function and survival of human adult skeletal
stem cells. Cells from three patients who were undergoing elective hip replacement
were harvested and incubated for two hours with 1% lidocaine, 0.5%
levobupivacaine or 0.5% bupivacaine hydrochloride solutions. Viability
was quantified using WST-1 and DNA assays. Viability and morphology
were further characterised using CellTracker Green/Ethidium Homodimer-1
immunocytochemistry and function was assessed by an alkaline phosphatase
assay. An additional group was cultured for a further seven days
to allow potential recovery of the cells after removal of the local
anaesthetic. A statistically significant and dose dependent reduction in cell
viability and number was observed in the cell cultures exposed to
all three local anaesthetics at concentrations of 25% and 50%, and
this was maintained even following culture for a further seven days. This study indicates that certain local anaesthetic agents in
widespread clinical use are deleterious to skeletal progenitor cells
when studied
Hyaline articular cartilage has been known to
be a troublesome tissue to repair once damaged. Since the introduction
of autologous chondrocyte implantation (ACI) in 1994, a renewed
interest in the field of cartilage repair with new repair techniques
and the hope for products that are regenerative have blossomed.
This article reviews the basic science structure and function of
articular cartilage, and techniques that are presently available
to effect repair and their expected outcomes.
We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.
Perilesional changes of chronic focal osteochondral defects were assessed in the knees of 23 sheep. An osteochondral defect was created in the main load-bearing region of the medial condyle of the knees in a controlled, standardised manner. The perilesional cartilage was evaluated macroscopically and biopsies were taken at the time of production of the defect (T0), during a second operation one month later (T1), and after killing animals at three (T3; n = 8), four (T4; n = 8), and seven (T7; n = 8) months. All the samples were histologically assessed by the International Cartilage Repair Society grading system and Mankin histological scores. Biopsies were taken from human patients (n = 10) with chronic articular cartilage lesions and compared with the ovine specimens. The ovine perilesional cartilage presented with macroscopic and histological signs of degeneration. At T1 the International Cartilage Repair Society ‘Subchondral Bone’ score decreased from a mean of 3.0 ( The perilesional cartilage in the animal model became chronic at one month and its histological appearance may be considered comparable with that seen in human osteochondral defects after trauma.
We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 μg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks. The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022). The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament.
Treatment strategies for osteoarthritis most commonly involve the removal or replacement of damaged joint tissue. Relatively few treatments attempt to arrest, slow down or reverse the disease process. Such options include peri-articular osteotomy around the hip or knee, and treatment of femoro-acetabular impingement, where early intervention may potentially alter the natural history of the disease. A relatively small proportion of patients with osteoarthritis have a clear predisposing factor that is both suitable for modification and who present early enough for intervention to be deemed worthwhile. This paper reviews recent advances in our understanding of the pathology, imaging and progression of early osteoarthritis.
