Osteoporosis is characterized by decreased trabecular bone volume, and microarchitectural deterioration in the medullary cavity. Blood and femoral bone marrow suspension Aims
Methods
Based on Ilizarov's law of tension-stress principle, distraction histogenesis technique has been widely applied in orthopaedic surgery for decades. Derived from this technique, cranial bone transport technique was mainly used for treating cranial deformities and calvarial defects. Recent studies reported that there are dense short vascular connections between skull marrow and meninges for immune cells trafficking, highlighting complex and tight association between skull and brain. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia without effective therapy. Meningeal lymphatics have been recognized as an important mediator in neurological diseases. The augmentation of meningeal lymphatic drainage might be a promising therapeutic target for AD. Our proof-of-concept study has indicated that cranial bone transport can promote ischemic stroke recovery via modulating meningeal lymphatic drainage function, providing a rationale for treating AD using cranial bone maneuver (CBM). This study aims to investigate the effects of CBM on AD and to further explore the potential mechanisms. Transgenic 5xFAD mice model was used in this study. After osteotomy, a bone flap was used to perform CBM without damaging the dura. Open filed test, novel object recognition test and Barn's maze test were used to evaluate neurological functions of 5xFAD mice after CBM treatment. Congo red and immunofluorescence staining were used to evaluate amyloid depositions and Aβ plaques in different brain regions. Lymphangiogenesis and the level of VEGF-C were examined after CBM treatment. OVA-A647 was intra-cisterna-magna injected to evaluate meningeal lymphatic drainage function after CBM treatment. CBM significantly improved memory functions and reduced amyloid depositions and Aβ plaques in the hippocampus of 5xFAD mice. A significant increase of meningeal lymphatic vessels in superior sagittal sinus and transverse sinus, and the upregulation of VEGF-C in meninges were observed in 5xFAD mice treated with CBM. Moreover, CBM remarkably enhanced meningeal lymphatic drainage function in 5xFAD mice (n=5-16 mice/group for all studies). CBM may promote meningeal lymphangiogenesis and lymphatic drainage function through VEGF-C-VEGFR3 pathway, and further reduce amyloid depositions and Aβ plaques and alleviate memory deficits in AD.
Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remain a challenge. A novel surgical technique named Tibial Cortex Transverse Transport has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In present study, we aimed to explore the wound healing effects after undergoing this novel technique via multiple ways. A novel rat model of Tibial Cortex Transverse Transport was established with a designed external fixator and effects on wound healing were investigated. All rats were randomized into 3 groups, with 12 rats per group: sham group (negative control), fixator group (positive control) and Tibial Cortex Transverse Transport group. Laser speckle perfusion imaging, vessel perfusion, histology and immunohistochemistry were used to evaluate the wound healing processes. Gross and histological examinations showed that Tibial Cortex Transverse Transport technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In Tibial Cortex Transverse Transport group, HE staining demonstrated a better epidermis and dermis recovery, while immune-histochemical staining showed that Tibial Cortex Transverse Transport technique promoted local collagen deposition. Tibial Cortex Transverse Transport technique also benefited to angiogenesis and immunomodulation. In Tibial Cortex Transverse Transport group, blood flow in the wound area was higher than that ofother groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the Tibial Cortex Transverse Transport group with double immune-labelling of CD31 and α-SMA. The M2 macrophages at the wound site in the Tibial Cortex Transverse Transport group was also increased. Tibial cortex transverse transport technique accelerated wound healing through enhanced angiogenesis and immunomodulation.
Abnormal lipid metabolism is involved in the development of osteoarthritis (OA). Growth differentiation factor 11 (GDF11) is crucial in inhibiting the differentiation of bone marrow mesenchymal stem cells into adipocytes. However, whether GDF11 participates in the abnormal adipogenesis of chondrocytes in OA cartilage is still unclear. Six-week-old female mice were subjected to unilateral anterior crossbite (UAC) to induce OA in the temporomandibular joint (TMJ). Histochemical staining, immunohistochemical staining (IHC), and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Primary condylar chondrocytes of rats were stimulated with fluid flow shear stress (FFSS) and collected for oil red staining, immunofluorescence staining, qRT-PCR, and immunoprecipitation analysis.Aims
Methods
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
Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remains a challenge. A novel surgical technique named ‘tibial cortex transverse transport’ (TTT) has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In the present study, we explored the potential biological mechanisms of TTT surgery using various techniques in a rat TTT animal model. A novel rat model of TTT was established with a designed external fixator, and effects on wound healing were investigated. Laser speckle perfusion imaging, vessel perfusion, histology, and immunohistochemistry were used to evaluate the wound healing processes.Aims
Methods
The use of 3D-printed titanium implant (DT) can effectively guide bone regeneration. DT triggers a continuous host immune reaction, including macrophage type 1 polarization, that resists osseointegration. Interleukin 4 (IL4) is a specific cytokine modulating osteogenic capability that switches macrophage polarization type 1 to type 2, and this switch favours bone regeneration. IL4 at concentrations of 0, 30, and 100 ng/ml was used at day 3 to create a biomimetic environment for bone marrow mesenchymal stromal cell (BMMSC) osteogenesis and macrophage polarization on the DT. The osteogenic and immune responses of BMMSCs and macrophages were evaluated respectively.Aims
Methods
Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).Aims
Methods
Over the past decades, computer-aided navigation system has experienced tremendous development for minimising the risks and improving the precision of the surgery. Nowadays, some commercially-available and self-developed surgical navigation systems have already been tested and proved successfully for clinical applications. However, all of these systems use computer screen to render the navigation information such as the real-time position and orientation of the surgical instrument, virtual path of preoperative surgical planning, so that the surgeons have to switch between the actual operation site and computer screen which is inconvenient and impact the continuity of surgery. In recent years, Augmented Reality (AR)- based surgical navigation is a promising technology for clinical applications. In the AR system, virtual and actual reality are mixed, offering real-time, high-quality visualisation of an extensive variety of information to the users. Therefore, in this study, a pilot study of a surgical navigation system for orthopaedics based on optical see-through augmented reality (AR-SNS) is presented, which encompasses the preoperative surgical planning, calibration, registration, and intra-operative tracking. With the aid of AR-SNS, the surgeon wearing the optical see-through head-mounted display can obtain a fused image that the 3D virtual critical anatomical structures are aligned with the actual structures of patient in intra-operative real-world scenario, so that some disadvantages of the traditional surgical navigation are overcome (For example, surgeon is no longer obliged to switch between the real operation scenario and computer screen), and the safety, accuracy, and reliability of the surgery may be improved.
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
More and more patients with end-stage knee OA are treated with total knee replacements (TKR). A modern TKR (Persona PS system, Zimmer Inc.) was designed with the hope to improve fit by providing additional sizing options on the femur and tibia. To date, there is very little information regarding the knee strength and knee mechanics during gait after the TKR. Furthermore, as a great percentage of knee OA patients have OA limited in one knee compartment and in the patellofemoral joint, a bi-compartmental knee replacement (BKR) (iDUO system, ConforMIS Inc.) was designed to treat OA at these affected areas. The BKR re-creates the individual's knee shape while correcting for any deformity. In addition, the BKR procedure results in less bone loss and retains the cruciate ligaments. To date, the influence of the BKR on knee strength and knee mechanics remains unknown. The purpose of the study was to evaluate knee strength and mechanics during level walking after the TKR and BKR surgeries. Twelve healthy control participants (age=57±6 yr.; mass=82±11 kg; height=175±11 cm), eight patients (age=63±10 yr.; mass=87±20 kg; height=166±8 cm) with ten BKR systems (post-op time = 17±9 mo.), and nine patients (age=65±9 yr.; mass=90±35 kg; Height=169±12 cm) with twelve TKR systems (post-op time = 14±5 mo.) participated in the study. In a laboratory setting, maximal isometric knee strength was evaluated. Motion capture and 3D kinematic and kinetic analyses were conducted for level walking. One way ANOVA was used to determine differences among the BKR, TKR, and the healthy control knees.Background
Methods
Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis.Objectives
Methods
To investigate the biomechanical mechanism and report preliminary clinical efficacy of eccentric rotational acetabular osteotomy (ERAO) when conduct treatment for developmental dysplasia of the hip (DDH). Biomechanical model of the hip joint was established on six female cadaveric hips embalmed by formalin and stimulate ERAO was then performed on the model. Vertical force was loaded on the cadaveric spine from 0 N to 500 N and strain value on femoral head was measured preoperatively and postoperatively when loading force on spine reached the point of 100, 200, 300, 400 and 500 N. Stress value were then calculated base on the measurements. Besides, we reported postoperative follow up cases which were underwent ERAO to treat DDH in our hospital from July 2007 to October 2014. A total of 25 patients (26 hips) were reported, including 6 males and 19 females. Age varies from 11 to 57 years old, and the average age was 31 years old. Postoperative hip function was evaluated by Harris hip score and anteroposterior X⁃ray of pelvic was taken preoperatively and postoperatively to measure the Acetabular⁃head index (AHI), CE angle and Sharp angle.Objective
Methods
To investigate the biomechanical basis and report preliminary clinical efficacy of eccentric rotational acetabular osteotomy (ERAO) when treating developmental dysplasia of the hip (DDH). Biomechanical model of the hip joint was established on cadaveric hips. After performed ERAO on the biomechanical model, we explored the impact of this surgery on biomechanics of the hip joint. Meanwhile, we reported postoperative follow-up cases who underwent ERAO in our hospital between November 2007 to July 2012. A total of 14 patients (15 hips) were reported, including 4 males and 10 females, mean age was 30 years old. Harris hip score was defined as clinical evaluation standard and radiographic assessment was based on the measurement and further comparison of pre- and post-operative AHI (Acetabular-head index), CE angle (Center-edge angle) and Sharp angle.Objective
Methods
Wear debris from articulating joint implants is inevitable. Small debris particles are phagocytosed by macrophages. Larger particles initiate the fusion of many macrophages into multi-nucleated giant cells for particle encasement. Macrophages are recruited into inflamed tissues from the circulating monocyte population. Approximately 10% of white blood cells are monocytes which after release from the bone marrow circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating MRP8/14 (S100A8/A9) is a measure of monocyte recruitment, part of the monocyte-endothelial docking complex, and shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of debris production. 2114 blood samples were collected from arthroplasty patients with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before their primary arthroplasty, 1187 patients > 1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in health adults are 0.5–3 mg/ml. Joint specific scores, WOMAC knee or Oxford Hip adjusted to percent of maximum, together with SF-12 were completed.Introduction:
Methods:
The risk factors for degenerative joint disease are well established: increasing age, obesity, joint abnormalities, trauma and overuse, together with female gender, ethnic and genetic factors. That obesity is a significant risk factor for developing osteoarthritis in non-weight-bearing as well as weight-bearing and joints was one of the first indications that the risk was nor purely that of aberrant biomechanical loading. Low grade chronic systemic inflammation is a component of each of ageing and obesity, atherosclerosis and diabetes, culminating in Metabolic Syndrome. In our study of 1684 patients with joint degeneration 85% were overweight or obese and 65% older than 65 years with 62% being both, 73% of patients were taking medications for serious, ‘non-orthopaedic’ health problems such as cardiovascular or respiratory disease, obesity or NIDDM. Monocytes are a major component of chronic inflammation, approximately 10% of white blood cells are monocytes which circulate for 2–3 days, before being recruited into tissues as inflammatory macrophages or undergoing apoptosis. Circulating S100A8/A9 (MRP8/14) is a measure of monocyte recruitment being shed during monocyte transmigration across the endothelium. The higher the S100A8/A9 the more monocytes being recruited giving an indirect measure of chronic inflammatory status. 2154 blood samples were collected from arthroplasty patients (first or second joint replacement), 1135 Female and 1019 Male, age 29–93 years, body mass index (BMI) 18–56, with hip or knee osteoarthritis (primary, post-traumatic and secondary), 589 before a primary arthroplasty, 1187 patients >1 year post-arthroplasty, 101 patients before revision for aseptic loosening and 237 patients >1 year post-revision. All study patients received metal on UHMWPE implants. Plasma S100A8/A9 was measured using BMA Biomedicals Elisa kit, normal levels in healthy adults are 0.5–3 mg/ml. The data were analysed using SPSS, p values were calculated using Spearman's test.Introduction:
Methods:
Internal fixation of fractures in the presence of osteopenia has been associated with a failure rate as high as 25%. Enhancing bone formation and osseointegration of orthopaedic hardware is a priority when treating patients with impaired bone regenerative capacity. Fibroblast Growth Factor (FGF) 18 regulates skeletal development and could therefore have applications in implant integration. This study was designed to determine if FGF 18 promotes bone formation and osseointegration in the osteopenic FGFR3−/− mouse and to examine its effect on bone marrow derived mesenchymal stem cells (MSCs). In Vivo: Intramedullary implants were fabricated from 0.4 × 10mm nylon rods coated with 300nm of titanium by physical vapour deposition. Skeletally mature, age matched female FGFR3−/− and wild type mice received bilateral intramedullary femoral implants. Left femurs received an intramedullary injection of 0.1μg of FGF 18 (Merck Serono), and right femurs received saline only. Six weeks later, femurs were harvested, radiographed, scanned by micro CT, and processed for undecalcified for histology. In Vitro: MSCs were harvested from femurs and tibiae of skeletally mature age matched FGFR3−/− and wild type mice. Cells were cultured in Alpha Modified Eagles Medium (αMEM) to monitor proliferation or αMEM supplemented with ascorbic acid and sodium beta-glycerophosphate to monitor differentiation. Proliferation was assessed through cell counts and metabolic activity at days 3, 6 and 9. Differentiation was assessed through staining for osteoblasts and mineral deposition at days 6, 9 and 12.Purpose
Method
All patients were allocated to a 3-week multidisciplinary functional restoration programme that emphasized biopsychosocial factors and included continuous tapering of opioid dose. During the study all patients kept records of the medication they used.
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.
