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
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
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
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
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
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
Introduction. Poor osseointegration of cementless implants is the leading clinical cause of implant loosening, subsidence, and replacement failure, which require costly and technically challenging revision surgery. The mechanism of osseointegration requires further elucidation. We have recently developed a novel titanium implant for the mouse tibia that maintains in vivo knee joint function and allows us to study osseointegration in an intra-articular, load-bearing environment. Vascular endothelial growth factor (VEGF) is one of the most important growth factors for regulation of vascular development and angiogenesis. It also plays critical roles in skeletal development and bone repair and regeneration. A specialized subset of vascular endothelium, CD31. hi. EMCN. hi. cells displaying high cell surface expression of CD31 and Endomucin, has been reported to promote osteoblast maturation and may be responsible for bone formation during development and fracture healing. Because of their potential role in osseointegration, the aim of this study was to use our mouse implant model to investigate the role of VEGF and CD31. hi. EMCN. hi. endothelium in osseointegration. Methods. Under an IACUC-approved protocol, the implant was inserted into the right tibia of 16-week-old female C57BL/6 mice (N = 38). The mice were then randomized into 2 groups: Control group (N=19) and Anti-VEGFR group (N=19). A cocktail of VEGFR-1 antibody (25mg/kg) and VEGFR-2 antibody (25mg/kg) was given to the mice in the Anti-VEGFR group by intraperitoneal injection every third day starting immediately after surgery until euthanasia. An equivalent amount of an isotype control antibody was given to the control group. Flow cytometric (N = 4/group) and immunofluorescencent (N = 3/group) analyses were performed at 2 weeks post-implantation to detect the distribution and density of CD31. hi. EMCN. hi. endothelium in the peri-implant bone. Pull-out testing was used at 4 weeks post-implantation to determine the strength of the bone-implant interface. Results. Flow cytometry revealed that Anti-VEGFR treatment decreased CD31. hi. EMCN. hi. vascular endothelium percentage in the peri-implant bone vs. control (p = 0.039) at 2 weeks post-implantation (Fig. 1). This was confirmed by the decrease of CD31 and EMCN double positive cells detected with immunofluorescence at the same time point (Fig. 2). More importantly, anti-VEGFR treatment decreased the maximum load of pullout testing compared with control (p = 0.042) (Fig. 3). Conclusion. VEGF is a key mediator of osseointegration and the development of CD31. hi. EMCN. hi. endothelium. This may provide a new drug target for the enhancement of osseointegration. We have also developed a system to run flow cytometric analysis and perform fluorescent staining on the limited tissue around the implant in this
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
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. For patients undergoing short knee arthroscopic procedures, a sterile calibrated pH probe was inserted into the anterior fascial compartment of the leg after skin preparation, but before tourniquet inflation. The limb was elevated for three minutes prior to tourniquet inflation to 250 mmHg or 300 mmHg. Intramuscular pH was recorded at one-second intervals throughout the procedure and for 20 minutes following tourniquet deflation. Probe-related adverse events were recorded.Aims
Methods
Vitamin E-infused highly cross-linked polyethylene (E1) has recently been introduced in total knee arthroplasty (TKA). An in vitro wear simulator study showed that E1 reduced polyethylene wear. However there is no published information regarding in vivo wear. Previous reports suggest that newly introduced materials which reduce in vitro polyethylene wear do not necessarily reduce in vivo polyethylene wear. To assist in the evaluation of the newly introduced material before widespread use, we established an in vivo polyethylene wear particle analysis for TKA. The aim of this study was to compare in vivo polyethylene wear particle generation between E1 and conventional polyethylene (ArCom) in TKA. A total of 34 knees undergoing TKA (17 each with ArCom or E1) were investigated. Except for the polyethylene insert material, the prostheses used for both groups were identical. Synovial fluid was obtained at a mean of 3.4 years (SD 1.3) postoperatively. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined by scanning electron microscopy.Aims
Methods
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. Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II.Aim
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
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
This Although many agents commonly injected into joints are chondrotoxic,
in this Cite this article:
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:
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:
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 clinical diagnosis of a partial tear of the
anterior cruciate ligament (ACL) is still subject to debate. Little
is known about the contribution of each ACL bundle during the Lachman
test. We investigated this using six fresh-frozen cadaveric lower
limbs. Screws were placed in the femora and tibiae as fixed landmarks
for digitisation of the bone positions. The femur was secured horizontally
in a clamp. A metal hook was screwed to the tibial tubercle and
used to apply a load of 150 N directed anteroposteriorly to the
tibia to simulate the Lachman test. The knees then received constant
axial compression and 3D knee kinematic data were collected by digitising
the screw head positions in 30° flexion under each test condition.
Measurements of tibial translation and rotation were made, first with
the ACL intact, then after sequential cutting of the ACL bundles,
and finally after complete division of the ACL. Two-way analysis
of variance analysis was performed. During the Lachman test, in all knees and in all test conditions,
lateral tibial translation exceeded that on the medial side. With
an intact ACL, both anterior and lateral tibial landmarks translated
significantly more than those on the medial side (p <
0.001).
With sequential division of the ACL bundles, selective cutting of
the posterolateral bundle (PLB) did not increase translation of
any landmark compared with when the ACL remained intact. Cutting the
anteromedial bundle (AMB) resulted in an increased anterior translation
of all landmarks. Compared to the intact ACL, when the ACL was fully
transected a significant increase in anterior translation of all
landmarks occurred (p <
0.001). However, anterior tibial translation
was almost identical after AMB or complete ACL division. We found that the AMB confers its most significant contribution
to tibial translation during the Lachman test, whereas the PLB has
a negligible effect on anterior translation. Section of the PLB
had a greater effect on increasing the internal rotation of the
tibia than the AMB. However, its contribution of a mean of 2.8°
amplitude remains low. The clinical relevance of our investigation
suggests that, based on anterior tibial translation only, one cannot distinguish
between a full ACL and an isolated AMB tear. Isolated PLB tears
cannot be detected solely by the Lachman test, as this bundle probably
contributes more resistance to the pivot shift.
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.