Our previous research has demonstrated that minor adjustments to in vitro cellular aggregation parameters, i.e. alterations to aggregate size, can influence temporal and spatial mineral depositions within maturing bone cell nodules. What remains unclear, however, is how aggregate size might affect mineralisation within said nodules over long-term in vivo culture. In this study, we used an osteoblast cell line, MLO-A5, and a primary cell culture, mesenchymal stem cells (MSC), to compare small (approximately 80 µm) with large (approximately 220 µm) cellular aggregates for potential bone nodule development after 8 weeks of culturing in a mouse model (n = 4 each group). In total, 30 chambers were implanted into the intra-peritoneal cavity of 20 male, immunocompromised mice (MF1-Nu/Nu, 4 – 5 weeks old). Nine small or three large aggregates were used per chamber. Neoveil mesh was seeded directly with 2 × 103 cells for monolayer control. At 8 weeks, the animals were euthanised and chambers fixed with formalin. Aggregate integrity and extracellular material growth were assessed via light microscopy and the potential mineralisation was assessed via micro-CT. Many large aggregates appeared to disintegrate, whilst the small aggregates maintained their form and produced additional extracellular material with increased sizes. Both MLO-A5 cells and MSC cells saw similar results. Interestingly, however, the MSCs were also seen to produce a significantly higher volume of dense material compared to the MLO-A5 cells from micro-CT analysis. Overall, a critical cell aggregate size appeared to exist balancing optimal tissue growth with oxygen diffusion, and cell source may influence differentiation pathway despite similar experimental parameters. The MSCs, for example, were likely producing bone via the endochondral ossification pathway, whilst the matured bone cells, MLO-A5 cells, were likely producing bone via the intramembranous ossification pathway.
The aim of this study was to investigate whether the type of cervical disc herniation influences the severity of symptoms at the time of presentation, and the outcome after surgical treatment. The type and extent of disc herniation at the time of presentation in 108 patients who underwent anterior discectomy for cervical radiculopathy were analyzed on MRI, using a four-point scale. These were dichotomized into disc bulge and disc herniation groups. Clinical outcomes were evaluated using the Neck Disability Index (NDI), 36-Item Short Form Survey (SF-36), and a visual analogue scale (VAS) for pain in the neck and arm at baseline and two years postoperatively. The perceived recovery was also assessed at this time.Aims
Methods
We aimed to evaluate the utility of 68Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with 99mTc-methylene bisphosphonates (99mTc-MDP) bone scan. We studied 39 patients with suspected PJI or AL. These patients underwent 68Ga-citrate PET/CT, 99mTc-MDP three-phase bone scan and single-photon emission CT (SPECT)/CT. PET/CT was performed at ten minutes and 60 minutes after injection, respectively. Images were evaluated by three nuclear medicine doctors based on: 1) visual analysis of the three methods based on tracer uptake model, and PET images attenuation-corrected with CT and those not attenuation-corrected with CT were analyzed, respectively; and 2) semi-quantitative analysis of PET/CT: maximum standardized uptake value (SUVmax) of lesions, SUVmax of the lesion/SUVmean of the normal bone, and SUVmax of the lesion/SUVmean of the normal muscle. The final diagnosis was based on the clinical and intraoperative findings, and histopathological and microbiological examinations.Aims
Methods
To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology.Aims
Methods
There is conflicting evidence on the safety of intra-articular injections of hyaluronic acid (HA) or corticosteroids (CSs) before total knee arthroplasty (TKA). We performed a meta-analysis of the relationship between intra-articular injections and subsequent infection rates after TKA. We searched PubMed, EMBASE, and the Cochrane Library for cohort studies that assessed the effect of preoperative injection of drugs into the joint cavity on the infection rate after TKA. The outcomes analyzed included the total infection rate, as well as those for different preoperative injection time periods and different drugs.Aims
Methods
To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI). This study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed.Aims
Methods
Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD. A total of 3,321 independent loci of gut microbiota were used to calculate the individual polygenic risk score (PRS) for 114 gut microbiota-related traits. The individual genotype data were obtained from UK Biobank cohort. Linear regressions were then conducted to evaluate the possible association of gut microbiota with L1-L4 BMD (n = 4,070), total BMD (n = 4,056), and femur total BMD (n = 4,054), respectively. PLINK 2.0 was used to detect the single-nucleotide polymorphism (SNP) × gut microbiota interaction effect on the risks of L1-L4 BMD, total BMD, and femur total BMD, respectively.Aims
Methods
MicroRNA-183 ( Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (Aims
Methods
Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Aims
Methods
Assess and characterise the suitability of a novel silk reinforced biphasic 3D printed scaffold for osteochondral tissue regeneration. Biphasic hybrid scaffolds consisted of 3D printed poly(ethylene glycol)-terephthalate-poly(butylene terephthalate)(PEGT/PBT) scaffold frame work (pore size 0.75mm), which has been infilled with a cast and freeze dried porous silk scaffold (5×5×2mm3), in addition to a seamless silk top layer (1mm). Silk scaffolds alone were used as controls. Both the biphasic and control scaffolds were characterised via uniaxial compression testing (strain rate 0.1mm/min), and the potential biocompatibility of the scaffolds was tested via in vitro culture of seeded bone marrow stromal cells post fabrication.Abstract
Objectives
Methods
Initial post-operative implant instability leads to impaired osseointegration, one of the most common reasons for aseptic loosening and revision surgery. In this study, we developed a novel murine model of implant instability and demonstrated the anabolic effect of immediate and delayed intermittent Parathyroid Hormone (iPTH) treatment in the setting of instability-induced osseointegration failure. 3D-printed titanium implants were inserted in an oversized drill-hole in the tibia of C57Bl/6 mice (n=54). After implantation, the mice were randomly divided in 3 treatment groups (control: PBS-vehicle; iPTH; delayed iPTH). Radiographic analysis was performed to confirm signs of implant loosening. Peri-implant tissue formation was assessed through histology. Osseointegration was assessed through µCT and biomechanical pullout testing.Introduction
Methods
Surgical failure, mainly caused by loosening implants, causes great mental and physical trauma to patients. Improving the physicochemical properties of implants to achieve favourable osseointegration will continue to be the focus of future research. Strontium (Sr), a trace element, is often incorporated into hydroxyapatite (HA) to improve its osteogenic activity. Our previous studies have shown that miR-21 can promote the osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway. The aim of this study is to fabricate a SrHA and miR-21 composite coating and it is expected to have a favorable bone healing capability. Ti discs (20 mm diameter and one mm thickness for the in vitro section) and rods (four mm diameter and seven mm length for the in vivo section) were prepared by machining pure Ti. The Ti cylinders were placed in a Teflon-lined stainless-steel autoclave for treating at 150°C for 24 h to form SrHA layer. The miR-21 was encapsulated in nanocapsules. The miR-21 nanocapsules were mixed with CMCS powder to form a gel-like sample and uniformly coated on the SrHA modifed Ti. Osteoblast-like MG63 cells were cultured on SrHA and miR-21 modified Ti, Cell proliferation activity and osteogenesis-related gene expression were evaluated. A bone defect model was established with mature New Zealand to evaluate the osseointegration. Cylindrical holes (four mm in diameter) were created at the distal femur and tibial plateau. Each rabbit was implanted with four of the aforementioned rods (distal femur and tibial plateau of the hind legs). After implantation for one, two and three months, the rabbits were observed by X-ray and scanned using u-CT. Histological and Immunohistochemical analysis were performed to examine the osteogenic markers. A biomechanical push-in test was used to assess the bone-implant bonding strength. Both SrHA nanoparticles with good superhydrophilicity and miR-21 nanocapsules with uniform sizes were distributed evenly on the surface of the Ti. In vitro experiments revealed that the composite coating was beneficial to osteoblast proliferation, differentiation and mineralization. In vivo evaluations demonstrated that this coating could not only promote the expression of angiogenic factor CD31 but also enhance the expression of osteoblastic genes to facilitate angio-osteogenesis. In addition, the composite coating also showed a decreased RANKL expression compared with the miR-21 coating. As a result, the SrHA/miR-21 composite coating promoted new bone formation and mineralization and thus enhanced osseointegration and bone-implant bonding strength. A homogeneous SrHA and miR-21 composite coating was fabricated by generating pure Ti through a hydrothermal process, followed by adhering miR-21 nanocapsules. This coating combined the favorable physicochemical properties of SrHA and miR-21 that synergistically promoted angiogenesis, osteogenesis, osseointegration, bone mineralization and thus bone-implant bonding strength. This study provided a new strategy for surface modification of biomedical implants.
Current treatments of prosthetic joint infection (PJI) are minimally effective against The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.Aims
Methods
PJI is a devastating complication following total joint arthroplasty. In this study, we explore the efficacy of a bacteriophage-derived lysin, PlySs2, against
Introduction
Methods
The aim of this study was to explore the prognostic factors for postoperative neurological recovery and survival in patients with complete paralysis due to neoplastic epidural spinal cord compression. The medical records of 135 patients with complete paralysis due to neoplastic cord compression were retrospectively reviewed. Potential factors including the timing of surgery, muscular tone, and tumour characteristics were analyzed in relation to neurological recovery using logistical regression analysis. The association between neurological recovery and survival was analyzed using a Cox model. A nomogram was formulated to predict recovery.Aims
Patients 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
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, CD31hiEMCNhi 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 CD31hiEMCNhi endothelium in osseointegration. 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 CD31hiEMCNhi 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.Introduction
Methods
The incidence of acute Achilles tendon rupture appears to be increasing. The aim of this study was to summarize various therapies for acute Achilles tendon rupture and discuss their relative merits. A PubMed search about the management of acute Achilles tendon rupture was performed. The search was open for original manuscripts and review papers limited to publication from January 2006 to July 2017. A total of 489 papers were identified initially and finally 323 articles were suitable for this review.Objectives
Methods
Poly-lactic acid (PLA) scaffolds are widely used in bone tissue engineering. The introduction of 3D printing has greatly increased the ability for tailoring different geometrical designs of these scaffolds for improved cellular attachment, growth and differentiation. This study aimed to investigate the effect of PLA fibre angle in 3D printed PLA scaffolds on hDPSC attachment and growth Two types of PLA scaffolds were prepared via 3D printing containing fibres angled at either 45° or 90°. hDPSCs (P4, 2*105 cells per scaffold) were statically seeded for 4 hours on to the scaffolds (7×3.5×3 mm3, n=3). Cellular attachment was checked using fluorescence microscopy and the number of unattached cells was counted using a haemocytometer (HCM). The cell-scaffold constructs were then cultured in osteogenic medium for up to 5 weeks. ALP staining and SEM were performed for one construct from each group at week 3. Cellular viability was determined using CMFDA/EHD1 live/dead labelling at week 4. After 5 weeks, constructs were processed for histology. Fluorescence micrographs showed high numbers of hDPSCs attached to scaffold surfaces in both groups after seeding irrespective of fibre angle. However, HCM cell count revealed that the 45° angled PLA scaffolds had significantly greater cell attachment compared to the 90° angled PLA group ( This study showed that 45° angled PLA 3D printed scaffolds enhanced hDPSC attachment and cellular bridging, which may help to rapidly close the macro-pores within the scaffold compared to the 90° angled group. This illustrates the potential of 45° angled 3D printed PLA scaffolds as good candidates for bone tissue engineering.
