Aims.
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
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. Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.Aims
Methods
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
This study investigated the effects of transcatheter arterial embolization (TAE) on pain, function, and quality of life in people with early-stage symptomatic knee osteoarthritis (OA) compared to a sham procedure. A total of 59 participants with symptomatic Kellgren-Lawrence grade 2 knee OA were randomly allocated to TAE or a sham procedure. The intervention group underwent TAE of one or more genicular arteries. The control group received a blinded sham procedure. The primary outcome was knee pain at 12 months according to the Knee injury and Osteoarthritis Outcome Score (KOOS) pain scale. Secondary outcomes included self-reported function and quality of life (KOOS, EuroQol five-dimension five-level questionnaire (EQ-5D-5L)), self-reported Global Change, six-minute walk test, 30-second chair stand test, and adverse events. Subgroup analyses compared participants who received complete embolization of all genicular arteries (as distinct from embolization of some arteries) (n = 17) with the control group (n = 29) for KOOS and Global Change scores at 12 months. Continuous variables were analyzed with quantile regression, adjusting for baseline scores. Dichotomized variables were analyzed with chi-squared tests.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
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
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
A limited number of investigations with conflicting results have described perivascular lymphocytic infiltration (PVLI) in the setting of total knee arthroplasty (TKA). The purpose of this study was to determine if PVLI found in TKAs at the time of aseptic revision surgery was associated with worse clinical outcomes and survivorship. A retrospective review was conducted on 617 patients who underwent aseptic TKA revision who had histological analysis for PVLI at the time of surgery. Clinical and radiological data were obtained pre- and postoperatively, six weeks postoperatively, and then every year thereafter.Aims
Methods
We propose a state-of-the-art temporary spacer, consisting of a cobalt-chrome (CoCr) femoral component and a gentamicin-eluting ultra-high molecular weight polyethylene (UHMWPE) tibial insert, which can provide therapeutic delivery of gentamicin, while retaining excellent mechanical properties. The proposed implant is designed to replace conventional spacers made from bone cement. Gentamicin-loaded UHMWPE was prepared using phase-separated compression moulding, and its drug elution kinetics, antibacterial, mechanical, and wear properties were compared with those of conventional gentamicin-loaded bone cement.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
The aims of this study were to compare the mean duration of antibiotic release and the mean zone of inhibition between vancomycin-loaded porous tantalum cylinders and antibiotic-loaded bone cement at intervals, and to evaluate potential intrinsic antimicrobial properties of tantalum in an Ten porous tantalum cylinders and ten cylinders of cement were used. The tantalum cylinders were impregnated with vancomycin, which was also added during preparation of the cylinders of cement. The cylinders were then placed on agar plates inoculated with MSSA. The diameter of the inhibition zone was measured each day, and the cylinders were transferred to a new inoculated plate. Inhibition zones were measured with a Vernier caliper and using an automated computed evaluation, and the intra- and interobserver reproducibility were measured. The mean inhibition zones between the two groups were compared with Wilcoxon’s test.Aims
Materials and Methods
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. An implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (n = 38). Mice received anti-VEGF receptor-1 (VEGFR-1) antibody (25 mg/kg) and VEGF receptor-2 (VEGFR-2) antibody (25 mg/kg; n = 19) or an isotype control antibody (n = 19). Flow cytometric (n = 4/group) and immunofluorescent (n = 3/group) analyses were performed at two weeks post-implantation to detect the distribution and density of CD31hiEMCNhi endothelium. RNA sequencing analysis was performed using sorted CD31hiEMCNhi endothelial cells (n = 2/group). Osteoblast lineage cells expressing osterix (OSX) and osteopontin (OPN) were also detected with immunofluorescence. Mechanical pull-out testing (n = 12/group) was used at four weeks post-implantation to determine the strength of the bone-implant interface. After pull-out testing, the tissue attached to the implant surface was harvested. Whole mount immunofluorescent staining of OSX and OPN was performed to determine the amount of osteoblast lineage cells.Aims
Materials and Methods
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. Cartilage defects were created in the load-bearing region of the lateral femoral condyle of mini-type pigs. The defects were repaired with traditional tissue-engineered cartilage, tissue-engineered cartilage constructed with the biotin-avidin (BA) technique, tissue-engineered cartilage constructed with the CBA technique and with autologous cartilage. The biomechanical properties, Western blot assay, histological findings and immunohistochemical staining were explored.Objectives
Methods
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
The purpose of this study was to compare clinical
outcomes of total knee arthroplasty (TKA) after manipulation under
anaesthesia (MUA) for post-operative stiffness with a matched cohort
of TKA patients who did not requre MUA. In total 72 patients (mean age 59.8 years, 42 to 83) who underwent
MUA following TKA were identified from our prospective database
and compared with a matched cohort of patients who had undergone
TKA without subsequent MUA. Patients were evaluated for range of
movement (ROM) and clinical outcome scores (Western Ontario and
McMaster Universities Arthritis Index, Short-Form Health Survey,
and Knee Society Clinical Rating System) at a mean follow-up of
36.4 months (12 to 120). MUA took place at a mean of nine weeks
(5 to 18) after TKA. In patients who required MUA, mean flexion
deformity improved from 10° (0° to 25°) to 4.4° (0° to 15°) (p <
0.001),
and mean range of flexion improved from 79.8° (65° to 95°) to 116°
(80° to 130°) (p <
0.001). There were no statistically significant
differences in ROM or functional outcome scores at three months,
one year, or two years between those who required MUA and those
who did not. There were no complications associated with manipulation At most recent follow-up, patients requiring MUA achieved equivalent
ROM and clinical outcome scores when compared with a matched control
group. While other studies have focused on ROM after manipulation,
the current study adds to current literature by supplementing this
with functional outcome scores. Cite this article:
A lack of connection between surgeons and patients in evaluating
the outcome of total knee arthroplasty (TKA) has led to the search
for the ideal patient-reported outcome measure (PROM) to evaluate
these procedures. We hypothesised that the desired psychometric properties
of the ideal outcome tool have not been uniformly addressed in studies describing
TKA PROMS. A systematic review was conducted investigating one or more facets
of patient-reported scores for measuring primary TKA outcome. Studies
were analysed by study design, subject demographics, surgical technique,
and follow-up adequacy, with the ‘gold standard’ of psychometric
properties being systematic development, validity, reliability,
and responsiveness.Objectives
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:
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:
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:
We report the clinical outcome and findings at
second-look arthroscopy of 216 patients (mean age 25 years (11 to 58))
who underwent anterior cruciate ligament (ACL) reconstruction or
augmentation. There were 73 single-bundle ACL augmentations (44
female, 29 male), 82 double-bundle ACL reconstructions (35 female,
47 male), and 61 single-bundle ACL reconstructions (34 female, 27
male). In 94 of the 216 patients, proprioceptive function of the knee
was evaluated before and 12 months after surgery using the threshold
to detect passive motion test. Second-look arthroscopy showed significantly better synovial
coverage of the graft in the augmentation group (good: 60 (82%),
fair: 10 (14%), poor: 3 (4%)) than in the other groups (p = 0.039).
The mean side-to-side difference measured with a KT-2000 arthrometer
was 0.4 mm (-3.3 to 2.9) in the augmentation group, 0.9 mm (-3.2
to 3.5) in the double-bundle group, and 1.3 mm (-2.7 to 3.9) in
the single-bundle group: the result differed significantly between
the augmentation and single-bundle groups (p = 0 .013). No significant
difference in the Lysholm score or pivot-shift test was seen between
the three groups (p = 0.09 and 0.65, respectively). In patients
with good synovial coverage, three of the four measurements used
revealed significant improvement in proprioceptive function (p = 0.177,
0.020, 0.034, and 0.026). We conclude that ACL augmentation is a reasonable treatment option
for patients with favourable ACL remnants. Cite this article:
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.
Lower limb muscle power is thought to influence outcome following
total knee replacement (TKR). Post-operative deficits in muscle
strength are commonly reported, although not explained. We hypothesised
that post-operative recovery of lower limb muscle power would be
influenced by the number of satellite cells in the quadriceps muscle at
time of surgery. Biopsies were obtained from 29 patients undergoing TKR. Power
output was assessed pre-operatively and at six and 26 weeks post-operatively
with a Leg Extensor Power Rig and data were scaled for body weight.
Satellite cell content was assessed in two separate analyses, the
first cohort (n = 18) using immunohistochemistry and the second
(n = 11) by a new quantitative polymerase chain reaction (q-PCR)
protocol for Pax-7 (generic satellite cell marker) and Neural Cell
Adhesion Molecule (NCAM; marker of activated cells).Objectives
Methods
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 compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery. Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p <
0.001) and functional score (p <
0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml ( We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery.
Haemophilia is an x-linked inherited bleeding disorder which can cause severe arthropathy. We have reviewed the results of 70 primary total knee replacements (TKR) performed in 57 haemophilic patients between 1983 and 2007. The functional results were assessed using the Hospital for Special Surgery (HSS) knee scoring system and Kaplan-Meier survivorship analysis. Six patients died. HSS scores were available for 60 TKRs at a mean follow-up of 9.2 years (2 to 23); 57 (95%) had good or excellent results. Deep infection was recorded in one patient. Kaplan-Meier analysis using infection and aseptic loosening as endpoints showed the survival rate at 20 years to be 94.0%. A reduction in infection, spontaneous haemarthrosis and improvement in the quality of life were noted to justify surgery in our series of patients with a mean age of 43 (25 to 70). We have found that using the latest techniques of continuous infusion of clotting Factor have significantly helped to reduce the complication rates and have achieved results which match those of the non-haemophilic population undergoing TKR.