Cartilage repair in terms of replacement, or regeneration of damaged or diseased articular cartilage with functional tissue, is the ‘holy grail’ of joint surgery. A wide spectrum of strategies for cartilage repair currently exists and several of these techniques have been reported to be associated with successful clinical outcomes for appropriately selected indications. However, based on respective advantages, disadvantages, and limitations, no single strategy, or even combination of strategies, provides surgeons with viable options for attaining successful long-term outcomes in the majority of patients. As such, development of novel techniques and optimisation of current techniques need to be, and are, the focus of a great deal of research from the basic science level to clinical trials. Translational research that bridges scientific discoveries to clinical application involves the use of animal models in order to assess safety and efficacy for regulatory approval for human use. This review article provides an overview of animal models for cartilage repair. Cite this article: Bone Joint Res 2014;4:89–94

Objectives. Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model. Methods. T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis. Results. T2DM rats had higher mean osteoarthritis scores than the control rats in each of the four areas that were analysed. However, only the results at the medial and lateral femur and medial tibia were significant. Cysts were also found in T2DM rats at the junction of the articular cartilage and subchondral bone. Immunohistochemical analysis does not show an increase in collagen II between control and T2DM rats. Mass comparisons also showed a significant relationship between mass and osteoarthritis score. Conclusions. T2DM was found to cause global degeneration in the UCD rat knee joints, suggesting that diabetes itself is a factor in the onset and progression of osteoarthritis. The immunohistochemistry stains showed little to no change in collagen II degeneration between T2DM and control rats. Overall, it seems that the animal model used is pertinent to future studies of T2DM in the development and progression of osteoarthritis. Cite this article: Bone Joint Res 2014;3:203–11

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Aims. To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. Methods. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm. 2. , 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens. Results. In the histopathological analysis, the macro-morphological grading scale showed a significant increase, while the histological score and cartilage repair scale of ESWT exhibited a significant decrease compared to OCD at the 8- and 12-week timepoints. At the 12-week follow-up, ESWT exhibited a significant improvement in the volume of damaged bone compared to OCD. Furthermore, immunohistochemistry analysis revealed a significant decrease in type I collagen and a significant increase in type II collagen within the newly formed hyaline cartilage following ESWT, compared to OCD. Finally, SRY-box transcription factor 9 (SOX9), aggrecan, and TGF-β, BMP-2, -3, -4, -5, and -7 were significantly higher in ESWT than in OCD at 12 weeks. Conclusion. ESWT promoted the effect of TGF-β/BMPs, thereby modulating the production of extracellular matrix proteins and transcription factor involved in the regeneration of articular cartilage and subchondral bone in an OCD rat model. Cite this article: Bone Joint Res 2024;13(7):342–352

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

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

Objective . Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint. Methods. A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. . Results. From the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections. Conclusion. The results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies. Cite this article: Bone Joint Res 2015;4:1–5

Objectives. To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. Methods. Anterior cruciate ligament reconstruction using the plantaris tendon as graft material was performed on both knees of 24 rabbits (48 knees) to mimic ACL reconstruction by two different suspensory fixation devices for graft fixation. For the adjustable fixation device model (Socket group; group S), a 5 mm deep socket was created in the lateral femoral condyle (LFC) of the right knee. For the fixed-loop model (Tunnel group; group T), a femoral tunnel penetrating the LFC was created in the left knee. Animals were sacrificed at four and eight weeks after surgery for histological evaluation and biomechanical testing. Results. Histologically, both groups showed a mixture of direct and indirect healing patterns at four weeks, whereas only indirect healing patterns were observed in both groups at eight weeks. No significant histological differences were seen between the two groups at four and eight weeks in the roof zone (four weeks, S: mean 4.8 . sd. 1.7, T: mean 4.5 . sd. 0.5, p = 0.14; eight weeks, S: mean 5.8 . sd. 0.8, T: mean 4.8 . sd. 1.8, p = 0.88, Mann-Whitney U test) or side zone (four weeks, S: mean 5.0 . sd. 1.2, T: mean 4.8 . sd. 0.4, p = 0.43; eight weeks, S: mean 5.3 . sd. 0.8,T: mean 5.5 . sd. 0.8, p = 0.61, Mann-Whitney U test) . Similarly, no significant difference was seen in the maximum failure load between group S and group T at four (15.6 . sd. 9.0N and 13.1 . sd. 5.6N) or eight weeks (12.6 . sd. 3.6N and 17.1 . sd. 6.4N, respectively). Conclusion. Regardless of bone tunnel configuration, tendon-bone healing after ACL reconstruction primarily occurred through indirect healing. No significant histological or mechanical differences were observed between adjustable and fixed-loop femoral cortical suspension methods. Cite this article: Y. Sato, R. Akagi, Y. Akatsu, Y. Matsuura, S. Takahashi, S. Yamaguchi, T. Enomoto, R. Nakagawa, H. Hoshi, T. Sasaki, S. Kimura, Y. Ogawa, A. Sadamasu, S. Ohtori, T. Sasho. The effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament reconstruction: An animal study. Bone Joint Res 2018;7:327–335. DOI: 10.1302/2046-3758.75.BJR-2017-0238.R2

Aims

The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Aims

This systematic review and meta-analysis aimed to compare the influence of patellar resurfacing following cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) on the incidence of anterior knee pain, knee-specific patient-reported outcome measures, complication rates, and reoperation rates.

Aims

To map literature on prognostic factors related to outcomes of revision total knee arthroplasty (rTKA), to identify extensively studied factors and to guide future research into what domains need further exploration.

Aims

To evaluate whether low-intensity pulsed ultrasound (LIPUS) accelerates bone healing at osteotomy sites and promotes functional recovery after open-wedge high tibial osteotomy (OWHTO).

Aims

Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release.

Aims

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.

We investigated whether strontium-enriched calcium phosphate cement (Sr-CPC)-treated soft-tissue tendon graft results in accelerated healing within the bone tunnel in reconstruction of the anterior cruciate ligament (ACL). A total of 30 single-bundle ACL reconstructions using tendo Achillis allograft were performed in 15 rabbits. The graft on the tested limb was treated with Sr-CPC, whereas that on the contralateral limb was untreated and served as a control. At timepoints three, six, nine, 12 and 24 weeks after surgery, three animals were killed for histological examination. At six weeks, the graft–bone interface in the control group was filled in with fibrovascular tissue. However, the gap in the Sr-CPC group had already been completely filled in with new bone, and there was evidence of the early formation of Sharpey fibres. At 24 weeks, remodelling into a normal ACL–bone-like insertion was found in the Sr-CPC group. Coating of Sr-CPC on soft tissue tendon allograft leads to accelerated graft healing within the bone tunnel in a rabbit model of ACL reconstruction using Achilles tendon allograft. Cite this article: Bone Joint J 2013;95-B:923–8

Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed. Cite this article: Bone Joint J 2013;95-B:301–4

Aims

Unicompartmental and total knee arthroplasty (UKA and TKA) are successful treatments for osteoarthritis, but the solid metal implants disrupt the natural distribution of stress and strain which can lead to bone loss over time. This generates problems if the implant needs to be revised. This study investigates whether titanium lattice UKA and TKA implants can maintain natural load transfer in the proximal tibia.

Objectives. The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. Methods. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8

This animal study compares different methods of performing an osteotomy, including using an Erbium-doped Yttrium Aluminum Garnet laser, histologically, radiologically and biomechanically. A total of 24 New Zealand rabbits were divided into four groups (Group I: multihole-drilling; Group II: Gigli saw; Group III: electrical saw blade and Group IV: laser). A proximal transverse diaphyseal osteotomy was performed on the right tibias of the rabbits after the application of a circular external fixator. The rabbits were killed six weeks after the procedure, the operated tibias were resected and radiographs taken. . The specimens were tested biomechanically using three-point bending forces, and four tibias from each group were examined histologically. Outcome parameters were the biomechanical stability of the tibias as assessed by the failure to load and radiographic and histological examination of the osteotomy site. . The osteotomies healed in all specimens both radiographically and histologically. The differences in the mean radiographic (p = 0.568) and histological (p = 0.71) scores, and in the mean failure loads (p = 0.180) were not statistically significant between the groups. . Different methods of performing an osteotomy give similar quality of union. The laser osteotomy, which is not widely used in orthopaedics is an alternative to the current methods. Cite this article: Bone Joint J 2015;97-B:1628–33

Aims

Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect.

Aims

Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes.

Aims

Tourniquets have potential adverse effects including postoperative thigh pain, likely caused by their ischaemic and possible compressive effects. The aims of this preliminary study were to determine if it is possible to directly measure intramuscular pH in human subjects over time, and to measure the intramuscular pH changes resulting from tourniquet ischaemia in patients undergoing knee arthroscopy.

Aims

MRI has been suggested as an objective method of assessing anterior crucate ligament (ACL) graft “ligamentization” after reconstruction. It has been proposed that the MRI appearances could be used as an indicator of graft maturity and used as part of a return-to-sport assessment. The aim of this study was to evaluate the correlation between MRI graft signal and postoperative functional scores, anterior knee laxity, and patient age at operation.

Animal studies have shown that implanted anterior cruciate ligament (ACL) grafts initially undergo a process of revascularisation prior to remodelling, ultimately increasing mechanical strength. We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans. We undertook a randomised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-strand hamstring tendon grafts. Randomised by the use of sealed envelopes, 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method. Three patients were excluded from the study. All patients underwent MR scanning postoperatively at 2, 6 and 12 months, together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee (IKDC) evaluation. All observations were made by investigators blinded to the surgical technique. Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament. Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months (paired t-test, p = 0.002). There was a significant reduction of mid-substance signal six months after the minimal debridement technique (paired t-test, p = 0.00007). No statistically significant differences were found in tunnel placement, incidence of Cyclops lesions, blood loss, IKDC scores, range of movement or Lachman test between the two groups

Aims

Proliferation, migration, and differentiation of anterior cruciate ligament (ACL) remnant and surrounding cells are fundamental processes for ACL reconstruction; however, the interaction between ACL remnant and surrounding cells is unclear. We hypothesized that ACL remnant cells preserve the capability to regulate the surrounding cells’ activity, collagen gene expression, and tenogenic differentiation. Moreover, extracorporeal shock wave (ESW) would not only promote activity of ACL remnant cells, but also enhance their paracrine regulation of surrounding cells.

Aims

Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function.

Aims

The purpose of this study was to explore the correlation between femoral torsion and morphology of the distal femoral condyle in patients with trochlear dysplasia and lateral patellar instability.

Aims

It is increasingly appreciated that coordinated regulation of angiogenesis and osteogenesis is needed for bone formation. How this regulation is achieved during peri-implant bone healing, such as osseointegration, is largely unclear. This study examined the relationship between angiogenesis and osteogenesis in a unique model of osseointegration of a mouse tibial implant by pharmacologically blocking the vascular endothelial growth factor (VEGF) pathway.

Aim

Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model.

Aims

The aim of this study was to evaluate the surface damage, the density of crosslinking, and oxidation in retrieved antioxidant-stabilized highly crosslinked polyethylene (A-XLPE) tibial inserts from total knee arthroplasty (TKA), and to compare the results with a matched cohort of standard remelted highly crosslinked polyethylene (XLPE) inserts.

Objectives

The primary stability of the cementless Oxford Unicompartmental Knee Replacement (OUKR) relies on interference fit (or press fit). Insufficient interference may cause implant loosening, whilst excessive interference could cause bone damage and fracture.

The aim of this study was to identify the optimal interference fit by measuring the force required to seat the tibial component of the cementless OUKR (push-in force) and the force required to remove the component (pull-out force).

Objectives

The lack of effective treatment for cartilage defects has prompted investigations using tissue engineering techniques for their regeneration and repair. The success of tissue-engineered repair of cartilage may depend on the rapid and efficient adhesion of transplanted cells to a scaffold. Our aim in this study was to repair full-thickness defects in articular cartilage in the weight-bearing area of a porcine model, and to investigate whether the CD44 monoclonal antibody biotin-avidin (CBA) binding technique could provide satisfactory tissue-engineered cartilage.

Aims

Different methods of anterior cruciate ligament (ACL) reconstruction have been described for skeletally immature patients before closure of the growth plates. However, the outcome and complications following this treatment remain unclear. The aim of this systematic review was to analyse the outcome and complications of different techniques which may be used for reconstruction of the ACL in these patients.

Objectives

The objective of this study was to determine if the use of fascia lata as a tendon regeneration guide (placed into the tendon canal following harvesting the semitendinosus tendon) would improve the incidence of tissue regeneration and prevent fatty degeneration of the semitendinosus muscle.

Aims

There are two techniques widely used to determine the rotational alignment of the components in total knee arthroplasty (TKA); gap balancing (GB) and measured resection (MR). Which technique is the best remains controversial. We aimed to investigate this in a systematic review and meta-analysis.

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 cartilage regeneration. Nevertheless, this study provided a sufficient basis to proceed to further clinical testing.

Cite this article: Bone Joint J 2015;97-B:924–32.

Objectives

The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping.

This in vivo controlled laboratory study was performed to evaluate various intra-articular clinical injection regimes that might be less toxic than some in vitro studies suggest. We hypothesised that low-concentration, preservative-free, pH-balanced agents would be less toxic than high-concentration non-pH-balanced agents with preservatives, and that injections of individual agents are less toxic than combined injections. The left knees of 12- to 13-week-old Sprague–Dawley rats were injected once with eight different single agents, including low and high concentrations of ropivacaine and triamcinolone, alone and in combination, as well as negative and positive controls. The rats were killed at one week or five months, and live–dead staining was performed to quantify the death of chondrocytes. All injections except pH-balanced 0.2% ropivacaine combined with preservative-free 1 mg/ml triamcinolone acetonide resulted in statistically significant decreases in chondrocyte viability, compared with control knees, after one week and five months (p < 0.001). After one week there was no significant difference in viability between 0.2% and 0.5% ropivacaine; however, 4 mg/ml triamcinolone resulted in a lower viability than 1 mg/ml triamcinolone.

Although many agents commonly injected into joints are chondrotoxic, in this in vivo study diluting preservative-free 10 mg/ml triamcinolone 1:9 in 0.2% pH-balanced ropivacaine resulted in low toxicity.

Cite this article: Bone Joint J 2015; 97-B:933–8.

Aim

Nail patella syndrome (NPS) is a skeletal dysplasia with patellofemoral dysfunction as a key symptom. We present the first in-depth radiological evaluation of the knee in a large series of NPS patients and describe the typical malformations.

Injury to the anterior cruciate ligament (ACL) is one of the most devastating and frequent injuries of the knee. Surgical reconstruction is the current standard of care for treatment of ACL injuries in active patients. The widespread adoption of ACL reconstruction over primary repair was based on early perception of the limited healing capacity of the ACL. Although the majority of ACL reconstruction surgeries successfully restore gross joint stability, post-traumatic osteoarthritis is commonplace following these injuries, even with ACL reconstruction. The development of new techniques to limit the long-term clinical sequelae associated with ACL reconstruction has been the main focus of research over the past decades. The improved knowledge of healing, along with recent advances in tissue engineering and regenerative medicine, has resulted in the discovery of novel biologically augmented ACL-repair techniques that have satisfactory outcomes in preclinical studies. This instructional review provides a summary of the latest advances made in ACL repair.

Cite this article: Bone Joint Res 2014;3:20–31.

We examined whether enamel matrix derivative (EMD) could improve healing of the tendon–bone interface following reconstruction of the anterior cruciate ligament (ACL) using a hamstring tendon in a rat model. ACL reconstruction was performed in both knees of 30 Sprague-Dawley rats using the flexor digitorum tendon. The effect of commercially available EMD (EMDOGAIN), a preparation of matrix proteins from developing porcine teeth, was evaluated. In the left knee joint the space around the tendon–bone interface was filled with 40 µl of EMD mixed with propylene glycol alginate (PGA). In the right knee joint PGA alone was used. The ligament reconstructions were evaluated histologically and biomechanically at four, eight and 12 weeks (n = 5 at each time point). At eight weeks, EMD had induced a significant increase in collagen fibres connecting to bone at the tendon–bone interface (p = 0.047), whereas the control group had few fibres and the tendon–bone interface was composed of cellular and vascular fibrous tissues. At both eight and 12 weeks, the mean load to failure in the treated specimens was higher than in the controls (p = 0.009). EMD improved histological tendon–bone healing at eight weeks and biomechanical healing at both eight and 12 weeks. EMD might therefore have a human application to enhance tendon–bone repair in ACL reconstruction.

The anatomy and microstructure of the menisci allow the effective distribution of load across the knee. Meniscectomy alters the biomechanical environment and is a potent risk factor for osteoarthritis. Despite a trend towards meniscus-preserving surgery, many tears are irreparable, and many repairs fail.

Meniscal allograft transplantation has principally been carried out for pain in patients who have had a meniscectomy. Numerous case series have reported a significant improvement in patient-reported outcomes after surgery, but randomised controlled trials have not been undertaken.

It is scientifically plausible that meniscal allograft transplantation is protective of cartilage, but this has not been established clinically to date.

Cite this article: Bone Joint J 2015; 97-B:590–4.

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors.

Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Cite this article: Bone Joint J 2014;96-B:1319–24.

Two-stage revision surgery for infected total knee replacement offers the highest rate of success for the elimination of infection. The use of articulating antibiotic-laden cement spacers during the first stage to eradicate infection also allows protection of the soft tissues against excessive scarring and stiffness. We have investigated the effect of cyclical loading of cement spacers on the elution of antibiotics. Femoral and tibial spacers containing vancomycin at a constant concentration and tobramycin of varying concentrations were studied in vitro. The specimens were immersed and loaded cyclically to 250 N, with a flexion excursion of 45°, for 35 000 cycles. The buffered solution was sampled at set intervals and the antibiotic concentration was established so that the elution could be calculated. Unloaded samples were used as a control group for statistical comparison.

The elution of tobramycin increased proportionately with its concentration in cement and was significantly higher at all sampling times from five minutes to 1680 minutes in loaded components compared with the control group (p = 0.021 and p = 0.003, respectively). A similar trend was observed with elution of vancomycin, but this failed to reach statistical significance at five, 1320 and 1560 minutes (p = 0.0508, p = 0.067 and p = 0.347, respectively). However, cyclically loaded and control components showed an increased elution of vancomycin with increasing tobramycin concentration in the specimens, despite all components having the same vancomycin concentration. The concentration of tobramycin influences both tobramycin and vancomycin elution from bone cement. Cyclical loading of the cement spacers enhanced the elution of vancomycin and tobramycin.

Smoking is known to have an adverse effect on wound healing and musculoskeletal conditions. This case-controlled study looked at whether smoking has a deleterious effect in the outcome of autologous chondrocyte implantation for the treatment of full thickness chondral defects of the knee.

The mean Modified Cincinatti Knee score was statistically significantly lower in smokers (n = 48) than in non-smokers (n = 66) both before and after surgery (p < 0.05). Smokers experienced significantly less improvement in the knee score two years after surgery (p < 0.05). Graft failures were only seen in smokers (p = 0.016). There was a strong negative correlation between the number of cigarettes smoked and the outcome following surgery (Pearson’s correlation coefficient −0.65, p = 0.004).

These results suggest that patients who smoke have worse pre-operative function and obtain less benefit from this procedure than non-smokers. The counselling of patients undergoing autologous chondrocyte implantation should include smoking, not only as a general cardiopulmonary risk but also because poorer results can be expected in smokers following this procedure.

Objectives

To assess the effectiveness of a modified tibial tubercle osteotomy as a treatment for arthroscopically diagnosed chondromalacia patellae.

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.

We have shown in a previous study that patients with combined lesions of the anterior cruciate (ACL) and medial collateral ligaments (MCL) had similar anteroposterior (AP) but greater valgus laxity at 30° after reconstruction of the ACL when compared with patients who had undergone reconstruction of an isolated ACL injury. The present study investigated the same cohort of patients after a minimum of three years to evaluate whether the residual valgus laxity led to a poorer clinical outcome.

Each patient had undergone an arthroscopic double-bundle ACL reconstruction using a semitendinosus-gracilis graft. In the combined ACL/MCL injury group, the grade II medial collateral ligament injury was not treated. At follow-up, AP laxity was measured using a KT-2000 arthrometer, while valgus laxity was evaluated with Telos valgus stress radiographs and compared with the uninjured knee. We evaluated clinical outcome scores, muscle girth and time to return to activities for the two groups.

Valgus stress radiographs showed statistically significant greater mean medial joint opening in the reconstructed compared with the uninjured knees (1.7 mm (sd 0.9) versus 0.9 mm (sd 0.7), respectively, p = 0.013), while no statistically significant difference was found between the AP laxity and the other clinical parameters. Our results show that the residual valgus laxity does not affect AP laxity significantly at a minimum follow up of three years, suggesting that no additional surgical procedure is needed for the medial collateral ligament in combined lesions.

Metallosis is a rare cause of failure after total knee replacement and has only previously been reported when there has been abnormal metal-on-metal contact. We describe 14 patients (15 knees) whose total knee replacement required revision for a new type of early failure caused by extensive metallosis. A modification of a cementless rotating platform implant, which had previously had excellent long-term survival, had been used in each case. The change was in the form of a new porous-beaded surface on the femoral component to induce cementless fixation, which had been used successfully in the fixation of acetabular and tibial components. This modification appeared to have resulted in metallosis due to abrasive two-body wear. The component has subsequently been recalled and is no longer in use. The presentation, investigation, and findings at revision are described and a possible aetiology and its implications are discussed.

We have investigated the changes in anterior laxity of the knee in response to direct electrical stimulation of eight normal and 45 reconstructed anterior cruciate ligaments (ACLs). In the latter, the mean time from reconstruction was 26.7 months (24 to 32). The ACL was stimulated electrically using a bipolar electrode probe during arthroscopy. Anterior laxity was examined with the knee flexed at 20° under a force of 134 N applied anteriorly to the tibia using the KT-2000 knee arthrometer before, during and after electrical stimulation.

Anterior tibial translation in eight normal and 17 ACL-reconstructed knees was significantly decreased during stimulation, compared with that before stimulation. In 28 knees with reconstruction of the ACL, in 22 of which the grafts were found to have detectable somatosensory evoked potentials during stimulation, anterior tibial translation was not decreased. These findings suggest that the ACL-hamstring reflex arc in normal knees may contribute to the functional stability and that this may not be fully restored after some reconstructions of the ACL.