This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA). Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2-△△CT method. All data were processed using SPSS software.Objectives
Methods
The length of the tourniquet time during total knee arthroplasty (TKA) is related to the incidence of post-operative deep vein thrombosis (DVT). Our aim in this study was to investigate the effect of the early release of the tourniquet on the incidence of DVT in patients undergoing TKA. A total of 200 patients who underwent TKA between November 2015 and November 2016 were prospectively enrolled. The tourniquet was inflated before surgery and released immediately after the introduction of the components (early release group). This group was compared with a retrospective cohort of 200 primary TKAs, in which the tourniquet was released after the dressings had been applied (late release group). The presence of a DVT was detected using bilateral lower limb ultrasonography. Peri-operative clinical and follow-up data were collected for analysis.Objectives
Methods
Osteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis. We conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.Objectives
Methods
Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO.Objectives
Methods
An equal knee joint height during flexion and extension is of critical importance in optimizing soft-tissue balancing following total knee arthroplasty (TKA). However, there is a paucity of data regarding the in-vivo knee joint height behavior. This study evaluated in-vivo heights and anterior-posterior (AP) translations of the medial and lateral femoral condyles before and after a cruciate-retaining (CR)-TKA using two flexion axes: surgical transepicondylar axis (sTEA) and geometric center axis (GCA). Eleven patient with advanced medial knee osteoarthritis (age: 51–73 years) who scheduled for a CR TKA and 9 knees from 8 healthy subjects (age: 23–49 years) were recruited. 3D models of the tibia and femur were created from their MR images. Dual fluoroscopic images of each knee were acquired during a weight-bearing single leg lunge. The OA knee was imaged again one year after surgery using the fluoroscopy during the same weight-bearing single leg lunge. The in vivo positions of the knee along the flexion path were determined using a 2D/3D matching technique. The GCA and sTEA were determined based on existing methods. Besides the anterior-posterior translation, the femoral condyle heights were determined using the distances from the medial and lateral epicondyle centers on the sTEA and GCA to the tibial plateau surface in coronal plane (Fig. 1). The paired t-test was applied to compare the medial and lateral condyle motion within each group (Healthy, OA, and CR-TKA). Two-way ANOVA followed post hoc Newman–Keuls test was adopted to detect significant differences among the groups. p<0.05 was considered significant.Introduction
Methods
In native knees anterior cruciate ligament (ACL) and asymmetric shape of the tibial articular surface with a convex lateral plateau are responsible for differential medial and lateral femoral rollback. Contemporary ACL retaining total knee arthroplasty (TKA) improves knee function over ACL sacrificing (CR) TKA; however, these implants do not restore the asymmetric tibial articular geometry. This may explain why ACL retention addresses paradoxical anterior sliding seen in CR TKA, but does not fully restore medial pivot motion. To address this, an ACL retaining biomimetic implant, was designed by moving the femoral component through healthy in vivo kinematics obtained from bi-planar fluoroscopy and sequentially removing material from a tibial template. We hypothesized that the biomimetic articular surface together with ACL preservation would better restore activity dependent kinematics of normal knees, than ACL retention alone. Kinematic performance of the biomimetic BCR design (asymmetric tibia with convex lateral surface), a contemporary BCR implant (symmetric shallow dished tibia) and a contemporary CR implant (symmetric dished tibia) was analyzed using KneeSIM software. Chair-sit, deep knee bend, and walking were analyzed. Components were mounted on an average bone model created from magnetic resonance imaging (MRI) data of 40 normal knees. Soft-tissue insertions were defined on the average knee model based on MRI data, and mechanical properties were obtained from literature. Femoral condyle center motions relative to the tibia were tracked to compare different implant designs.INTRODUCTION
METHODS
Combined acetabular and femoral anteversion (CA) of the hip following total hip arthroplasty (THA) is critical to the hip function and longevity of the components. However, no study has been reported on the accuracy in restoration of CA of the hip after operation using robotic assistance and conventional free-hand techniques. The purpose of this study was to evaluate if using robotic assistance in THA can better restore native CA than a free-hand technique. Twenty three unilateral THA patients participated in this study. Twelve of them underwent a robotic-arm assisted THA (RIO® Robotic Arm Interactive Orthopedic System, Stryker Mako., Fort Lauderdale, FL, USA) and eleven received a free-hand THA. Subject specific 3D models of both implanted and non-implanted hips were reconstructed using post-operative CT scans. The anteversion and inclination of the native acetabulum and implanted cup were measured and compared. To determine the differences of the femoral anteversion between sides, the non-implanted native femur was mirrored and aligned with the remaining femur of the implanted side using an iterative closest point algorithm. The angle between the native femoral neck axis and the prosthesis neck axis in transverse plane was measured as the change in femoral anteversion following THA. The sum of the changes of the acetabular and femoral anteversion was defined as the change of CA after THA. A Wilcoxon signed rank test was performed to test if the anteversion of the navigation and free-hand THAs were different from the contralateral native hips (α = 0.05). The acetabular anteversion were 22.0°±7.4°, 35.9°±6.5° and 32.6°±22.6° for the native hips, robotic assisted THAs and free-hand THAs, respectively, and the corresponding values of the acetabular inclinations were 52.0°±2.9°, 35.4°±4.4° and 43.1°±7.1°. The acetabular anteversion was increased by 12.2°±11.1° (p=0.005) and 12.5°±20.0° (p=0.102) for the robotic assisted and the free-hand THAs. The femoral anteversion was increased by 6.3°±10.5° (p=0.077) and 11.0°±13.4° (p=0.014) for the robotic assisted and free-hand THAs, respectively. The CA were significantly increased by 18.5°±11.7° (p<0.001) and 23.5°±26.5° (p=0.019) for the robotic assisted and the free-hand THAs. The changes of the CA of the free-hand THAs varied in a larger range than those of the robotic assisted THAs. This study is the first to evaluate the changes in acetabular and femoral anteversions of the hips after robotic assisted and free-hand THAs using the contralateral native hip as a control. The results demonstrate that both the navigation and free-hand THAs significantly increased the CA compared to the contralateral native hips, but the changes of the robotic assisted THAs (18.5°±11.7°) were smaller and varied less than those of the free-hand THAs (23.5°±26.5°). These data suggest that the robotic assisted THA can better restore the native hip CAs with higher repeatability than the free-hand technique. Further studies are needed to investigate the effects of the hip anteversion changes on the
Umbilical cord derived stem cell secretion could enhance the osteogenic differentiation of human bone marrow stem cells. It may promote bone, cartilage and tendon regeneration in rat models, but the effect was not significant up to now. Mesenchymal stem cells (MSCs) are multipotent cells that have extensive proliferative capacity. MSCs synthesise various exosomes, growth factors and cytokines. Stem cell secretions were made from serum free conditioned medium of stem cells collected from different human tissues, such as adipose tissue and dental pulp. Our hypothesis is umbilical cord stem cell secretion could promote multiple proliferation and differentiation of MSCs, also enhance the regeneration of musculoskeletal tissues.Summary Statement
Introduction
Contemporary PCL sacrificing Total Knee Arthroplasty (TKA) implants (CS) consist of symmetric medial and lateral tibial articular surfaces with high anterior lips designed to substitute for the stability of the native PCL. However, designs vary significantly across implant systems in the level of anteroposterior constraint provided. Therefore, the goal of this study was to investigate kinematics of two CS designs with substantially different constraint levels. The hypothesis was that dynamic knee simulations could show the effect of implant constraint on kinematics of CS implants. LifeModeler KneeSIM software was used to analyze contemporary CS TKA (X) with a symmetric and highly dished tibia and contemporary CS TKA (Y) with a symmetric tibia having flat sections bounded by high anterior and posterior lips, during simulated deep knee bend and chair sit. The flat sections of CS-Y implant are designed to allow freedom prior to motion restriction by the implant lips. Components were mounted on an average knee model created from Magnetic Resonance Imaging (MRI) data of 40 normal knees. Relevant ligament/tendon insertions were obtained from the MRI based 3D models and tissue properties were based on literature values. The condyle center motions relative to the tibia were used to compare the different implant designs. In vivo knee kinematics of healthy subjects from published literature was used for reference.INTRODUCTION
METHODS
While kinematic abnormalities of contemporary TKA implants have been well established, a solution has not yet been achieved. We hypothesized that contemporary TKA implants are not compatible with normal soft-tissue function and normal knee motion. We propose a novel technique for reverse engineering advanced implant articular surfaces (biomimetic surface), by using accurate 3D kinematics of normal knees. This technique accounts for surgical placement of the implants, and allows design of tibial and femoral articular surfaces in conjunction. Magnetic resonance imaging was used to create 3D knee models of 40 normal subjects (24 male, 16 female, age 29.9 ± 9.7 years), and bi-planar fluoroscopy was used to capture 3D knee motion during a deep knee bend. These data were combined to create a 3D virtual representation of an average normal knee and its motion pathway. A TKA femoral component was mounted on the average knee, and moved through its normal kinematic pathway to carve out an articular surface from a tibial template (Fig. 1 and 2). The geometry of the resulting biomimetic tibia was compared to that of the native tibia, and a contemporary TKA tibial insert that uses the same femoral component.Introduction:
Methods:
Due to technology advancement, many studies have reported on in-vivo human knee kinematics recently (Dannis, 2005; Moro-oka, 2008; Tashman, 2003; Koo, 2008). This abstract summarized the joint kinematics during three motions usually seen in our daily living, i.e. gait, step-up (stair ascending) and single-legged lunge that was measured using a combined dual-fluoroscopic imaging system and MRI based modeling technique (Li, 2008). Cartilage contacts or condylar motion using transepicondylar axis (TEA)/geometric center axis (GCA) were used to describe the motion characters of the knee during these motions. In the treadmill gait, the movement of the medial femoral condyle along the anteroposterior direction was significantly greater than that of the lateral femoral condyle during the stance phase using either TEA (9.7 ± 0.7 mm vs. 4.0 ± 1.7 mm, respectively; p < 0.01; Fig. 1A) or GCA (17.4 ± 2.0 mm vs. 7.4 ± 6.1 mm, respectively; p < 0.01; Fig. 1B). A “lateral-pivoting” of the knee was observed (Kozanek, 2009). In the step-up motion, both medial and lateral contact points moved anteriorly on the tibial articular surfaces along the step-up motion path. The contact points on the medial and lateral tibial plateau moved anteriorly (13.5 ± 3.2 mm vs. 10.7 ± 5.0 mm, respectively; p > 0.05; Fig. 2A) with knee extension. Using the TEA (Fig. 2B), the femoral condylar motions presented a similar pattern as the contact points; nonetheless, using the GCA (Fig. 2C), the femoral condylar motion pattern was dramatically different. The medial condyle moved anteriorly, while the lateral condyle shifted posteriorly. However, none of them showed a significant pivoting phenomenon (Li, 2013). In the single-legged lunge, both medial and lateral contact points moved similarly before 120° of knee flexion, but the lateral contact moved posteriorly and significantly more than the medial compartment in high flexion (1.9 ± 2.1 mm vs. 4.8 ± 2 mm, respectively; p < 0.05). The single-legged lunge didn't show a single motion pattern (Fig. 3) (Qi, 2013). These data provide baseline knowledge for the understanding of normal physiological function of the knee during gait, step-up and lunge activities. The findings of these studies demonstrated that knee joint kinematics is activity-dependent and indicated that the knee joint motions could not be described using a single motion character such as “medial-pivoting” that has recently been popularized in total knee arthroplasty design areas.
Contemporary Posterior Cruciate Ligament (PCL) retaining TKA implants (CR) are associated with well-known kinematic deficits, such as absence of medial pivot motion, paradoxical anterior femoral sliding, and posterior femoral subluxation at full extension. The hypothesis of this study was that a biomimetic implant, reverse engineered by using healthy knee kinematics to carve the tibial articular surface, could restore normal kinematic patterns of the knee. Kinematics of the biomimetic CR and two contemporary CR implants (A, B) were evaluated during simulated deep knee bend and chair-sit in LifeModeler KneeSIM™ software. Anteroposterior motion of the medial and lateral femoral condyle centers was measured relative to a tibial origin. The implants were mounted on an average knee model created from magnetic resonance imaging (MRI) of 40 healthy knees. The medial and lateral collateral ligaments, posterior cruciate ligament, quadriceps mechanism, and the overall capsular tension were modeled. The soft-tissue insertions were obtained from the average knee model, and the mechanical properties were obtained from literature. In vivo knee kinematics of healthy subjects from published literature was used for reference.Introduction:
Methods:
ACL retaining (BCR) Total Knee Arthroplasty (TKA) provides more normal kinematics than ACL sacrificing (CR) TKA. However, in the native knee the ACL and the asymmetric shape of the tibial articular surface with a convex lateral plateau are responsible for the differential medial/lateral femoral rollback (medial pivot). Therefore, the hypothesis of this study was that an asymmetric biomimetic articular surface together with ACL preservation would better restore native knee kinematics than retention of the ACL alone. Normal knee kinematics from bi-planar fluoroscopy was used to reverse engineer the tibial articular surface of the biomimetic implant. This was achieved by moving the femoral component through the healthy knee kinematics and removing material from a tibial template. LifeModeler KneeSIM software was used to analyze a biomimetic BCR implant (asymmetric tibia with convex lateral surface), a contemporary BCR (symmetric shallow dished tibia) and a contemporary CR (symmetric dished tibia) implant during simulated deep knee bend and chair sit. Components were mounted on an average bone model created from Magnetic Resonance Imaging (MRI) data of 40 normal knees. The soft-tissue insertions were obtained from the average knee model and the mechanical properties were obtained from literature. Femoral condyle center motions relative to the tibia were used to compare different implant designs. In vivo knee kinematics of healthy subjects from published literature was used for reference.INTRODUCTION
METHODS
Ten percent of fractures end in delayed or non-union. NSAIDs have been linked to an inhibitory action on fracture repair for three decades yet the mechanism of action remains to be elucidated. Cancer research has identified that NSAIDs impede cell proliferation by inhibiting angiogenesis. It is proposed that a similar mechanism occurs in the induction of NSAID induced non-union. We have investigated this hypothesis in a randomised placebo control trial of the NSAID rofecoxib using a murine femoral fracture. All animals had an open femoral fracture treated using an external fixator. Outcomes measures included x-ray, histology and biomechanical testing, with laser Doppler used to assess blood flow across the fracture gap. Radiology showed similar healing patterns in both groups; however, at the later stages (day 32) the NSAID group had significantly poorer healing. Histological analysis showed that controls healed quicker (days 24 and 32), with more callus (day 8) and less fibrous tissue (Day 32). Biomechanical testing showed controls were stronger at day 32. Both groups exhibited a similar pattern of blood flow; however NSAIDs exhibited a lower median flow from day 4 onwards (significant at days 4, 16 and 24). Positive correlations were demonstrated between both histological and radiographic assessments of healing, with increasing blood flow. NSAID animals exhibited lower flows and poorer healing by all outcomes. Regression analysis demonstrates, however, that the negative effect of NSAIDs on fracture repair is independent of its inhibitory action on blood flow. COX-2 inhibitors are marketed as having cleaner side effect profiles and are widely used in trauma patients. Following development of a novel method of analysing functional vascularity across a fracture gap, we have demonstrated that the COX-2 inhibitor rofecoxib has a significant negative effect on blood flow at the fracture gap alongside inhibiting fracture repair.
Thrombin related peptide (TP 508) is a 23 amino-acid synthetic peptide that mimics a portion of the receptor-binding domain of the human thrombin molecule. Thrombin triggers both proteolytic activated receptors and non proteolytic activated receptors to bring about a mixture of responses ranging from tissue breakdown and clot formation, to new vessel formation and tissue repair. TP 508 stimulates only the non proteolytic activated receptors, and this initiates repair and angiogenesis but not clot formation or tissue breakdown Previous studies have shown that TP508 can stimulate repair in the dermal and musculoskeletal tissues by promoting angiogenesis and enhancing the proliferation and migration of cells. High energy fractures are associated with a delay in healing. We hypothesized that high energy fracture healing would be improved with the use of TP508, and that the dose and site of application would have importance.
24 animals were sacrificed on day 21 and the remaining 56 mice on day 35. Of the 35 day old animals 8 in each group had both femora harvested and the biomechanical properties were tested using the 3-point bending technique. Specimens from the 21 day old animals and remaining 35 day old animals were used for histological analysis. All 80 animals had digital radiographs taken each week. Using image analysis software five pixel density graphs were generated across each fracture gap. A validated semi quantitative analysis was used to score each graph and the total accumulated for each radiograph. The width of the fracture calus was measured and expressed as a ratio of the femur diameter.
Radiographic analysis showed greater healing of fracture and callus formation in Group I compared to Groups II, III, and IV, at both three and five weeks post-fracture (P<
0.05). Histological analysis showed an increase in bone formation in group I compared to the other groups.
Once damaged, articular cartilage has limited capacity for self-repair due to their avascular and acellular nature. Tissue engineering approaches using cultured chondrocytes and biomaterials as scaffoldings hold promises for repairing cartilage defects. However, the source of articular chondrocytes is limited and the chon-drocytes may de-differentiate when cultured for a prolonged period. Bone marrow derived mesenchymal stem cells (BMSCs) have multi-differentiation potentials and autologous BMSCs are easy to obtain and culture with no/little immunological reaction when re-implanted. 24 NZW rabbits were used. Rabbit autologous BMSCs were obtained through marrow aspirations and expanded in culture under the chondrogenic induction media (DMEM, 10% FCS, plus 10ng/ml TGF-β1) for 3 weeks. A full-thickness articular cartilage defect (3 mm in diameter and 3 mm in depth) was created on both medial condyles in the rabbit. For experimental group (16 joints), the defects were filled immediately with alginate capsules containing autologous chondrogenic cells (8.5 x 104); for the control groups, the defects were filled with either alginate capsules alone (16 joints) or left untreated (16 joints). All the animals were terminated at 6 and 12 weeks after surgery and the cartilage samples were harvested for histology, immunochemistry and in situ hybridization examinations. For histology, in the experimental group the defects were filled with immature hyaline-like cartilaginous tissues at 6 weeks; by 12 weeks the newly formed cartilage showing signs of remodeling and integrating into the surrounding articular cartilage. The expression of type II collagen in the newly formed cartilaginous tissues was confirmed by immunohistochemistry and by in situ hybridization methods. In the control groups, the defects were mainly filled with fibrous tissues in all the animals at the two time points examined. We have used Wakitani cartilage grading system for semi-quantitative histological evaluation. Significant lower scores (with superior histology) were found in the experimental group comparing to the two control groups. Our results confirmed that full-thickness articular cartilage defects can be repaired by chondrogenically differentiated autologous BMSCs seeded into alginate capsules. Further studies are ongoing to explore the long term outcome of this treatment approach as well as using new scaffolds for cartilage tissue engineering.
The thrombin-related peptide, TP508, a synthetic 23 amino acid peptide, has been shown to promote soft tissue, cartilage and fracture repair. We have previously demonstrated that two injections of TP508 have signifi-cantly enhanced bone consolidation in a rabbit model of distraction osteogenesis. This study was to test if a single injection of TP508 in a slow-releasing preparation will have the similar effects. Unilateral tibial osteoectomies were stabilized with M100 Orthofix lengtheners in 17 male adult NZW rabbits. After 7 days, lengthening was initiated at a rate of 1.4 mm/day for 6 days. The following treatments were given: Group 1: TP508 in saline (300ug/300ul, n=6) was injected into the osteotomy gap at day of surgery and into the lengthening gap at end of lengthening. Group 2 (Control): Dextran gel (300ul, n=6) and Group 3: 300ul Dextran gel mixed with microspheres containing 300ug TP508 (n=5), was injected into the lengthening gap at end of lengthening. All animals were terminated 2 weeks after lengthening. Bone formation was assessed by weekly radiography and the specimens were subject to pQCT, microCT and histology examinations. On radiographies there was more bone formation in the TP508 treated groups than that of the control group at 1st week post-lengthening and complete union was seen in 50% rabbits in Group 1, 33% in Group 2, and 60% in Group 3 at termination. The mean BMD of the regenerates was significantly higher in the TP508 treated groups than that of the control group (p<
0.05). MicroCT analysis demonstrated advanced bone formation in the TP508 treated animals. For histology, the regenerates were mainly consisted of woven bone of neocortilization and callus remodelling in Groups 1 and 3, whereas in Group 2, focal defects with cartilaginous tissues were frequently seen. In conclusion we have demonstrated that a single injection of TP508 in the form of slow releasing micro-spheres has enhanced bone consolidation during distraction osteogenesis. TP508 may therefore be applied in the slow-releasing preparation for augmenting bone formation at reduced doses, costs and risks of infections through repeated injections.
Mesenchymal stem cells (MSCs) are immunosuppressive and have been used to facilitate tissue repair in the context of allogeneic implantation. However, xenogeneic cell transplantation has not been fully explored. The present study investigated the feasibility of xenogeneic MSCs implantation in mice. MSCs were harvested from the bone marrow of GFP rats (Green Fluorescent Protein transgenic rats), and cultured as previously described. 1 million GFP MSCs were loaded onto the synthetic HA/TCP porous Skelite blocks and implanted intramuscularly into the quadriceps of the MF1 and SCID mice. After 11 weeks, the implants were harvested and processed for histology examination. Upon termination, the mononuclear cells from the peripheral blood of each animal were also collected for mixed lymphocyte culture to examine lymphocyte proliferation potential and T-cell mediated cell lysis (cytotoxic) assays. In the SCID mice, there was sparse osteoid tissue formation in the implants, whereas only dense connective tissues were seen in the implants of the MF1 mice. Osteocalcin mRNA expression was confirmed in the osteoid tissues in the implants from the SCID mice, but it was not detected in the MF1 mice by RT in situ PCR examination. Cells of GFP-rat origin were observed in both the MF1 and SCID mice (more so in the SCID mice) after 11 weeks implantation, which were confirmed by positive immunostaining of anti-GFP antibody. In the MF1 mice after 11 weeks xenogeneic MSCs implantation, the rate of lymphocyte proliferation was significantly increased when mixed with the GFP-MSCs compared to that of mixed lymphocyte culture assays in the SCID or MF1 mice without xenogeneic MSCs implantation, suggesting that implantation of xenoge-neic MSCs has promoted host anti-graft immunogenic responses towards to otherwise immunosuppressive MSCs. In conclusion, xenogeneic rat MSCs transplanted in immunocompetent mice has survived for prolonged period, but their function was comprised to certain extent and this may be due to the increased host anti-graft immune sensitization after exposed to the xenogeneic MSCs.
