To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population. This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015-2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence. The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 12,156 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category. Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.
Treatment outcomes for methicillin-resistant Total knee arthroplasty (TKA), MRSA inoculation, debridement, and vancomycin-spacer implantation were performed successively in rats to mimic first-stage PJI during the two-stage revision arthroplasty procedure. Vancomycin was administered intraperitoneally or intra-articularly for two weeks to control the infection after debridement and spacer implantation.Aims
Methods
Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS).Aims
Methods
The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR.Aims
Methods
The superficial zone (SFZ) of articular cartilage has unique structural and biomechanical features, and is important for joint long-term function. Previous studies have shown that TGF-β/Alk5 signaling upregulating PRG4 expression maintains articular cartilage homeostasis. However, the exact role and molecular mechanism of TGF-β signaling in SFZ of articular cartilage homeostasis are still lacking. In this study, a combination of in vitro and in vivo approaches were used to elucidate the role of Alk5 signaling in maintaining the SFZ of articular cartilage and preventing osteoarthritis initiation. Mice with inducible cartilage SFZ-specific deletion of Alk5 were generated to assess the role of Alk5 in OA development. Alterations in cartilage structure were evaluated histologically. The chondrocyte apoptosis and cell cycle were detected by TUNEL and Edu staining, respectively. Isolation, culture and treatment of SFZ cells, the expressions of genes associated with articular cartilage homeostasis and TGF-β signaling were analyzed by qRT-PCR. The effects of TGF-β/Alk5 signaling on proliferation and differentiation of SFZ cells were explored by cells count and alcian blue staining. In addition, SFZ cells isolated from C57 mice were cultured in presence of TGF-β1 or SB505124 for 7 days and transplanted subcutaneously in athymic mice. Postnatal cartilage SFZ-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. qRT-PCR and IHC results confirmed that Alk5 gene was effectively deleted in articular cartilage SFZ cells. Next, the PRG4-positive cells in articular cartilage SFZ were significantly decreased in Alk5 cKO mice compared with those in Cre-negative control mice. The mRNA expression of Aggrecan and Col2 were decreased, meanwhile, expression of Mmp13 and Adamts5 were significantly increased in articular cartilage SFZ cells of Alk5 cKO mice. In addition, Edu and TUNEL staining results revealed that slow-cell cycle cell number and increase the apoptosis positive cell in articular cartilage SFZ of Alk5 cKO mice compared with Cre-negative mice, respectively. Furthermore, all groups of SFZ cells formed ectopic solid tissue masses 1 week after transplantation. Histological examination revealed that the TGF-β1-pretreated tissues was composed of small and round cells and was positive for alcian blue staining, while the SB505124-pretreated tissue contained more hypertrophic cells though it did stain with alcian blue. TGF-β/alk5 signaling is an essential regulator of the superficial layer of articular cartilage by maintaining chondrocyte number, its differentiation properties, and lubrication function. Furthermore, it plays a critical role in protecting cartilage from OA initiation.
This study aimed to uncover the hub long non-coding RNAs (lncRNAs) differentially expressed in osteoarthritis (OA) cartilage using an integrated analysis of the competing endogenous RNA (ceRNA) network and co-expression network. Expression profiles data of ten OA and ten normal tissues of human knee cartilage were obtained from the Gene Expression Omnibus (GEO) database (GSE114007). The differentially expressed messenger RNAs (DEmRNAs) and lncRNAs (DElncRNAs) were identified using the edgeR package. We integrated human microRNA (miRNA)-lncRNA/mRNA interactions with DElncRNA/DEmRNA expression profiles to construct a ceRNA network. Likewise, lncRNA and mRNA expression profiles were used to build a co-expression network with the WGCNA package. Potential hub lncRNAs were identified based on an integrated analysis of the ceRNA network and co-expression network. StarBase and Multi Experiment Matrix databases were used to verify the lncRNAs.Aims
Methods
Osteoarthritis (OA) is traditionally believed to affect the osteochondral unit by wear-and-tear from the superficial zone to the deep zone of cartilage and extended to subchondral plate. Obesity is commonly considered as a risk of OA development and hence total knee replacement (TKR), but the mechanism remains unclear. We hypothesized that obesity accelerated OA development by deteriorating tidemarks and increasing bone remodelling. 616,495 cases of TKR for OA from Australia and British joint replacement registries were collected, and data indicated that patients with higher BMI had TKR at earlier age. Specifically, patients with BMI ≤25kg/m2 showed 8 years younger than patients with BMI ≥40kg/m2 (P<0.0001) when they received TKR. We next examined tibia plateaus of 88 knee OA patients by micro-CT and histomorphometry. Linear regression showed that less cartilage degradation was associated with increased BMI in the load-bear compartment (p<0.05), while 58.3% of patients with BMI≥40kg/m2 demonstrated a clear anatomical separation close to tidemarks filled with fibrosis, erythrocytes and bone fragments (compared to BMI ≤25kg/m2 group: 7.7%, p<0.01). In subchondral bone, elevated bone formation was associated with increased BMI, as higher thickness of osteoid (p<0.01), percent osteoid volume (p<0.01), percent osteoid surface (p<0.01) were found in obese patients. However, no alteration of bone resorption and microstructural parameters was found to be associated with BMI. We suspected that the abnormal loading in knee joint due to high BMI led to the direct deterioration of binding site of osteochondral unit, which might be the mechanism of the rapid progression in obesity-related OA.
Bone ingrowth is desired with uncemented hip implants. Infection is clearly undesirable. We have worked on developing a nanofiber coating for implants that would enhance bone formation while inhibiting infection. Few studies have focused on developing an implant surface nanofiber (NF) coating to prevent infection and enhance osseointegration by local drug release. In this study, coaxial doxycycline (Doxy)-doped polycaprolactone/polyvinyl alcohol (PCL/PVA) Nanofibers were directly deposited on the titanium (Ti) implant surface during electrospinning. The interaction of loaded Doxy with both PVA and PCL NFs was characterized by Raman spectroscopy. The bonding strength of Doxy-doped NF coating on Ti implants was confirmed by a stand single-pass scratch test. The improved implant osseointegration by PCL/PVA NF coatings in vivo was confirmed by scanning electron microscopy, histomorphometry and micro computed tomography at 2, 4 and 8 weeks after implantation. The bone contact surface (%) changes of NF coating group (80%) is significantly higher than that of no NF group (< 5%, p<0.05). Finally, we demonstrated that Doxy-doped NF coating effectively inhibited bacterial infection and enhanced osseointegration in an infected (Staphylococcus aureus) tibia implantation rat model. Doxy released from NF coating inhibited bacterial growth up to 8 weeks in vivo. The maximal push-in force of Doxy-NF coating (38 N) is much higher than that of NF coating group (6.5 N) 8 weeks after implantation (p<0.05), which was further confirmed by quantitative histological analysis and micro computed tomography. These findings indicate that coaxial PCL/PVA NF coating doped with Doxy and/or other drugs have great potential in enhancing implant osseointegration and preventing infection.
Collagen scaffolds loaded with mesenchymal stem cells accelerate neurological recovery in rat spinal hemisection. To investigate the implantation effects of the collagen scaffold (CS) combined with mesenchymal stem cells (MSCs) on the function recovery of spinal cord injury (SCI) with a lateral hemisection SCI SD rat model.Summary
Objective
The objective of this study was to evaluate the rotation and
translation of each joint in the hindfoot and compare the load response
in healthy feet with that in stage II posterior tibial tendon dysfunction
(PTTD) flatfoot by analysing the reconstructive three-dimensional
(3D) computed tomography (CT) image data during simulated weight-bearing. CT scans of 15 healthy feet and 15 feet with stage II PTTD flatfoot
were taken first in a non-weight-bearing condition, followed by
a simulated full-body weight-bearing condition. The images of the
hindfoot bones were reconstructed into 3D models. The ‘twice registration’
method in three planes was used to calculate the position of the
talus relative to the calcaneus in the talocalcaneal joint, the
navicular relative to the talus in talonavicular joint, and the cuboid
relative to the calcaneus in the calcaneocuboid joint.Objective
Methods
The purpose of this study was to analyze the long-term effect of arterial perfusion of drugs and bone marrow stromal cells (bMSCs) on osteonecrosis of femoral head (ONFH). From Jan 1997 to Mar 2004, one hundred and seventeen patients with ONFH were consecutively enrolled to receive a digital subtraction angiography (DSA) in arteriae circumflexa femoris medialis and arteriae circumflexa femoris lateralis. In DSA, a dosage of drugs (urokinase, salvia injection, and tetramethylpyrazine) and autologous bMSCs or only the drugs were perfused into the arteries. The morphological changes of the arteries in DSA after perfusion were recorded. Symptoms radiographs, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at one month, six months, one year, 2 years and 5 years after the treatment. 83 patients were followed up for more than five years. The median follow-up period was 7.9 years. After the drugs had been perfuse, the arteries became thicker, and more than 2 branches appeared in DSA. Five years after the operation, the Harris hip score of 32 patients (38 hips) treated by arterial perfusion of simplex drugs (group A) increased from 59.24±5.28 to 71.80±6.37 (p<
0.01), and the excellent and good rate of centesimal evaluation was 57.9%. The Harris hip score of 51 patients (59 hips) treated by arterial perfusion of drugs and autologous bMSCs (group B) increased from 59.52±4.85 to 78.29±6.05 (p<
0.01), and the excellent and good rate was 78.0% which was significantly higher than that of group A (p=0.035). Since two years after operation, the Harris hip score of group A was significantly higher than that of group B (p<
0.01). Among the patients in group B, the rate of excellent and good in early stages (˜,˜ a and ˜ b according to Ficat classifying, 50 hips) was 84.0%, which was better than the rate in the terminal stage (Ficat III, 9 hips, the excellent and good rate was 44.4%)(p = 0.028), and the rate of excellent and good in low age group (<
40 years, 33 hips) was also better than that in high age group (≥ 40 years, 26 hips)(p=0.038). We conclude that arterial perfusion of drugs and autologous bMSCs treating osteonecrosis of femoral head is safe and effective. The long-term therapeutic effect is more satisfactory than that of simplex arterial perfusion of drugs.
Synthetic biodegradable polymers have been utilized increasingly in pharmaceutical, medical and biomedical engineering. Control of the interaction of living cells and biomaterials surfaces is one of the major goals in the design and development of new polymeric biomaterials in tissue engineering. In this study, a novel amphiphilic tri-block copolymer, methoxy-terminated poly (ethylene glycol) (MPEG) – polyL-lactide (PLLA) – polylysine (PLL) was synthesized. Various molecular compositions of tri-block copolymers were prepared via optimising the parameters and characterized through Nuclear Magnetic Resonance and Gel Permeation Chromatography. The tri-block copolymer was then mixed with high molecular weight PLLA to form a flat film. The surface properties measured by X-ray Photoelectron Spectroscopy and Atomic Force Microscopy demonstrated high content of the PLL on the surface of PLLA film, which indicated self-segregation of MPEG-b-PLLA-b-PLL on PLLA surface. No cytotoxicity was detected in triblock copolymers, and compared to pure PLLA and diblock copolymers, the triblock copolymers were much more effective for cell adhesion and proliferation. It was noted that the hydrophilic chain of PEG and PLL stretched out and formed an outer layer, especially under the aqueous environment, which resulted in enhanced cell attachment and proliferation. The self-segregation behaviour of MPEG-b-PLLA-b-PLL triblock copolymer shows a potential application in scaffold preparation of tissue engineering.
Interactions between cells and polymers are mediated by proteins, which are either secreted by cells and immobilized on the biomaterial surface, or absorbed from the medium. Poly (lactic acid) (PLA) is widely used in tissue engineering as a scaffold material, however anchorage-dependent cells such as osteoblasts do not attach, grow, and differentiate well on a hydrophobic surface. In this study, a hydrophilic polymer-poly (ethylene glycol) (PEG) was used to develop diblock polymers, Methoxy-terminated poly (ethylene glycol)-Poly (lactic acid) (MPEG-PLA) to investigate cell-biomaterial interactions. Osteoblasts were cultured on different composition of PEG-PLA films in serum free or serum condition. Lactate dehydrogense (LDH) assay was used to assess the cytotoxicity of the copolymers and cell attachment and proliferation on the polymer surfaces; furthermore cell morphology was visualized by Crystal Violet stain. The results showed that MPEG-PLA films induced early osteoblast attachment in serum free condition and the higher content of PEG in the MPEG-PLA films the more cell attachment was noticed. No significant difference of cell attachment was observed on MPEG-PLA films between serum free and 10% serum culture condition. Crystal Violet stain demonstrated the same trend in the cell-spreading characteristics on the polymer surface. In conclusion MPEG-PLA copolymer can enhance osteoblast attachment under serum-free condition, which implies a potential application in cell delivery therapy due to the restriction in animal products for human therapeutically goods.
The compressive strength of the MAA and MSA based copolymers was measured as a function of anhydride concentration. Compressive strength for MMA increased (90±9 to 140±10 Mpa) in an approximately linear manner for MAA concentrations from 10 to 40 wt.% but decreased markedly for MAA concentration of 45% (62±14 Mpa). The compressive strength of MSA decreased exponentially for concentrations ranging from 10 to 45 wt.% (140±18 to 39±1 Mpa).
Injection of PMMA bone cement into fractured vertebral bodies has been used clinically and proved to be effective. However, there are concerns about thermal injury to the cord and interferece of bone remodling .The purpose of this study is to use the biodegradable bone substitute as an alternative for augumentation of fractured vertebral bodies .