Aim. Mesenchymal
Adenosine, lidocaine, and Mg2+ (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. 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.Aims
Methods
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
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. 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/mm2, 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.Aims
Methods
This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.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
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. A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) – one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks.Aims
Methods
Thresholds of acceptable early migration of the components in total knee arthroplasty (TKA) have traditionally ignored the effects of patient and implant factors that may influence migration. The aim of this study was to determine which of these factors are associated with overall longitudinal migration of well-fixed tibial components following TKA. Radiostereometric analysis (RSA) data over a two-year period were available for 419 successful primary TKAs (267 cemented and 152 uncemented in 257 female and 162 male patients). Longitudinal analysis of data using marginal models was performed to examine the associations of patient factors (age, sex, BMI, smoking status) and implant factors (cemented or uncemented, the size of the implant) with maximum total point motion (MTPM) migration. Analyses were also performed on subgroups based on sex and fixation.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
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. A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.Aims
Methods
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. Cell viability, proliferation, migration, and expression levels of Collagen-I (COL-I) A1, transforming growth factor beta (TGF-β), and vascular endothelial growth factor (VEGF) were compared between ACL remnant cells untreated and treated with ESW (0.15 mJ/mm2, 1,000 impulses, 4 Hz). To evaluate the subsequent effects on the surrounding cells, bone marrow stromal cells (BMSCs)’ viability, proliferation, migration, and levels of Type I Collagen, Type III Collagen, and tenogenic gene (Aims
Methods
The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL. The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF).Aims
Methods
To compare the effect of femoral bone tunnel configuration on tendon-bone healing in an anterior cruciate ligament (ACL) reconstruction animal model. 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.Objectives
Methods
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, 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:
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. Bilateral semitendinosus tendons were harvested from rabbits using a tendon stripper. On the inducing graft (IG) side, the tendon canal and semitendinosus tibial attachment site were connected by the fascia lata, which was harvested at the same width as the semitendinosus tendon. On the control side, no special procedures were performed. Two groups of six rabbits were killed at post-operative weeks 4 and 8, respectively. In addition, three healthy rabbits were killed to obtain normal tissue. We evaluated the incidence of tendon tissue regeneration, cross-sectional area of the regenerated tendon tissue and proportion of fatty tissue in the semitendinosus muscle.Objectives
Materials and Methods
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:
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. 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.Objectives
Methods
Matrix-induced autologous chondrocyte implantation
(MACI) is an established technique used to treat osteochondral lesions
in the knee. For larger osteochondral lesions (>
5 cm2)
deeper than approximately 8 mm we have combined the use of two MACI
membranes with impaction grafting of the subchondral bone. We report
our results of 14 patients who underwent the ‘bilayer collagen membrane’
technique (BCMT) with a mean follow-up of 5.2 years (2 to 8). There
were 12 men and two women with a mean age of 23.6 years (16 to 40).
The mean size of the defect was 7.2 cm2 (5.2 to 12 cm2)
and were located on the medial (ten) or lateral (four) femoral condyles.
The mean modified Cincinnati knee score improved from 45.1 (22 to
70) pre-operatively to 82.8 (34 to 98) at the most recent review
(p <
0.05). The visual analogue pain score improved from 7.3
(4 to 10) to 1.7 (0 to 6) (p <
0.05). Twelve patients were considered
to have a good or excellent clinical outcome. One graft failed at
six years. The BCMT resulted in excellent functional results and durable
repair of large and deep osteochondral lesions without a high incidence
of graft-related complications.
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.
We describe 119 meniscal allograft transplantations performed concurrently with articular cartilage repair in 115 patients with severe articular cartilage damage. In all, 53 (46.1%) of the patients were over the age of 50 at the time of surgery. The mean follow-up was for 5.8 years (2 months to 12.3 years), with 25 procedures (20.1%) failing at a mean of 4.6 years (2 months to 10.4 years). Of these, 18 progressed to knee replacement at a mean of 5.1 years (1.3 to 10.4). The Kaplan-Meier estimated mean survival time for the whole series was 9.9 years ( The survival of the transplant was not affected by gender, the severity of cartilage damage, axial alignment, the degree of narrowing of the joint space or medial
Autologous chondrocyte implantation (ACI) is used widely as a treatment for symptomatic chondral and osteochondral defects of the knee. Variations of the original periosteum-cover technique include the use of porcine-derived type I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte implantation (MACI) using a collagen bilayer seeded with chondrocytes. We have performed a prospective, randomised comparison of ACI-C and MACI for the treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44 received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the clinical score after one year. The mean modified Cincinnati knee score increased by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic assessments performed after one year showed a good to excellent International Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts. Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year. The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6% (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group. We conclude that the clinical, arthroscopic and histological outcomes are comparable for both ACI-C and MACI. While MACI is technically attractive, further long-term studies are required before the technique is widely adopted.
