To assess the structure and extracellular matrix molecule expression of osteogenic cell sheets created via culture in medium with both dexamethasone (Dex) and ascorbic acid phosphate (AscP) compared either Dex or AscP alone. Osteogenic cell sheets were prepared by culturing rat bone marrow stromal cells in a minimal essential medium (MEM), MEM with AscP, MEM with Dex, and MEM with Dex and AscP (Dex/AscP). The cell number and messenger (m)RNA expression were assessed Objectives
Methods
Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage. Human articular cartilage was obtained from patients with and without OA, and chondrocytes were isolated and stimulated by IL-1β. The expression levels of miR-138-5p in cartilage and chondrocytes were both determined. After transfection with miR-138-5p mimics, allele-specific oligonucleotide (ASO)-miR-138-5p, or their negative controls, the messenger RNA (mRNA) levels of aggrecan (ACAN), collagen type II and alpha 1 (COL2A1), the protein levels of glycosaminoglycans (GAGs), and both the mRNA and protein levels of matrix metalloproteinase (MMP)-13 were evaluated. Luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot were performed to explore whether Forkhead Box C1 (FOCX1) was a target of miR-138-5p. Further, we co-transfected OA chondrocytes with miR-138-5p mimics and pcDNA3.1 (+)-FOXC1 and then stimulated with IL-1β to determine whether miR-138-5p-mediated IL-1β-induced cartilage matrix degradation resulted from targeting FOXC1.Objectives
Materials and Methods
Demineralised bone matrix (DBM) is rarely used for the local
delivery of prophylactic antibiotics. Our aim, in this study, was
to show that a graft with a bioactive glass and DBM combination,
which is currently available for clinical use, can be loaded with
tobramycin and release levels of antibiotic greater than the minimum
inhibitory concentration for Antibiotic was loaded into a graft and subsequently evaluated
for drug elution kinetics and the inhibition of bacterial growth.
A rat femoral condylar plug model was used to determine the effect
of the graft, loaded with antibiotic, on bone healing.Aims
Materials and Methods
The need for bone tissue supplementation exists in a wide range
of clinical conditions involving surgical reconstruction in limbs,
the spine and skull. The bone supplementation materials currently
used include autografts, allografts and inorganic matrix components;
but these pose potentially serious side-effects. In particular the
availability of the autografts is usually limited and their harvesting
causes surgical morbidity. Therefore for the purpose of supplementation
of autologous bone graft, we have developed a method for autologous
extracorporeal bone generation. Human osteoblast-like cells were seeded on porous granules of
tricalcium phosphate and incubated in osteogenic media while exposed
to mechanical stimulation by vibration in the infrasonic range of
frequencies. The generated tissue was examined microscopically following
haematoxylin eosin, trichrome and immunohistochemical staining.Objectives
Methods
Neurogenic heterotopic ossification (NHO) is
a disorder of aberrant bone formation affecting one in five patients sustaining
a spinal cord injury or traumatic brain injury. Ectopic bone forms
around joints in characteristic patterns, causing pain and limiting
movement especially around the hip and elbow. Clinical sequelae
of neurogenic heterotopic ossification include urinary tract infection,
pressure injuries, pneumonia and poor hygiene, making early diagnosis
and treatment clinically compelling. However, diagnosis remains
difficult with more investigation needed. Our pathophysiological
understanding stems from mechanisms of basic bone formation enhanced
by evidence of systemic influences from circulating humor factors
and perhaps neurological ones. This increasing understanding guides
our implementation of current prophylaxis and treatment including
the use of non-steroidal anti-inflammatory drugs, bisphosphonates,
radiation therapy and surgery and, importantly, should direct future, more
effective ones.
Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) Objectives
Materials and Methods
As the number of younger and more active patients
treated with total knee arthroplasty (TKA) continues to increase,
consideration of better fixation as a means of improving implant
longevity is required. Cemented TKA remains the reference standard
with the largest body of evidence and the longest follow-up to support
its use. However, cementless TKA, may offer the opportunity of a
more bone-sparing procedure with long lasting biological fixation
to the bone. We undertook a review of the literature examining advances
of cementless TKA and the reported results. Cite this article:
Construction of a functional skeleton is accomplished
through co-ordination of the developmental processes of chondrogenesis,
osteogenesis, and synovial joint formation. Infants whose movement Cite this article:
We conducted a case-control study to examine
the merit of silver-coated tumour prostheses. We reviewed 85 patients
with Agluna-treated (silver-coated) tumour implants treated between
2006 and 2011 and matched them with 85 control patients treated
between 2001 and 2011 with identical, but uncoated, tumour prostheses. In all, 106 men and 64 women with a mean age of 42.2 years (18.4
to 90.4) were included in the study. There were 50 primary reconstructions
(29.4%); 79 one-stage revisions (46.5%) and 41 two-stage revisions
for infection (24.1%). The overall post-operative infection rate of the silver-coated
group was 11.8% compared with 22.4% for the control group (p = 0.033,
chi-square test). A total of seven of the ten infected prostheses
in the silver-coated group were treated successfully with debridement,
antibiotics, and implant retention compared with only six of the
19 patients (31.6%) in the control group (p = 0.048, chi-square
test). Three patients in the silver-coated group (3.5%) and 13 controls
(15.3%) had chronic periprosthetic infection (p = 0.009, chi-square
test). The overall success rates in controlling infection by two-stage
revision in the silver-coated group was 85% (17/20) compared with
57.1% (12/21) in the control group (p = 0.05, chi-square test).
The Agluna-treated endoprostheses were associated with a lower rate
of early periprosthetic infection. These silver-treated implants
were particularly useful in two-stage revisions for infection and
in those patients with incidental positive cultures at the time
of implantation of the prosthesis. Debridement with antibiotic treatment and retention of the implant
appeared to be more successful with silver-coated implants. Cite this article:
Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone. We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.
This study aims to evaluate if micro-CT can work as a method for the 3D assessment and analysis of cancellous bone by comparing micro-CT with undecalcified histological sections in OVX rats. The mandible and tibia of sham, ovariectomised (OVX) and zoledronate-injected ovariectomised (OVX-ZOL) rats were assessed morphometrically. Specimens were scanned by micro-CT. Undecalcified histological sections were manufactured from the specimen scanned by micro-CT and stained with haematoxylin and eosin. Bivariate linear regressions and one-way analysis of variance were undertaken for statistics using SPSS 16.0.1 software.Objectives
Methods
In order to ensure safety of the cell-based therapy for bone
regeneration, we examined BM cells obtained from a total of 13 Sprague-Dawley (SD) green
fluorescent protein transgenic (GFP-Tg) rats were culture-expanded
in an osteogenic differentiation medium for three weeks. Osteoblast-like
cells were then locally transplanted with collagen scaffolds to
the rat model of segmental bone defect. Donor cells were also intravenously infused
to the normal Sprague-Dawley (SD) rats for systemic biodistribution.
The flow cytometric and histological analyses were performed for
cellular tracking after transplantation.Objectives
Methods
Pathological assessment of periprosthetic tissues is important, not only for diagnosis, but also for understanding the pathobiology of implant failure. The host response to wear particle deposition in periprosthetic tissues is characterised by cell and tissue injury, and a reparative and inflammatory response in which there is an innate and adaptive immune response to the material components of implant wear. Physical and chemical characteristics of implant wear influence the nature of the response in periprosthetic tissues and account for the development of particular complications that lead to implant failure, such as osteolysis which leads to aseptic loosening, and soft-tissue necrosis/inflammation, which can result in pseudotumour formation. The innate response involves phagocytosis of implant-derived wear particles by macrophages; this is determined by pattern recognition receptors and results in expression of cytokines, chemokines and growth factors promoting inflammation and osteoclastogenesis; phagocytosed particles can also be cytotoxic and cause cell and tissue necrosis. The adaptive immune response to wear debris is characterised by the presence of lymphoid cells and most likely occurs as a result of a cell-mediated hypersensitivity reaction to cell and tissue components altered by interaction with the material components of particulate wear, particularly metal ions released from cobalt-chrome wear particles. Cite this article: Professor N. A. Athanasou. The pathobiology and pathology of aseptic implant failure.
Induced membrane technique is a relatively new technique in the reconstruction of large bone defects. It involves the implantation of polymethylmethacrylate (PMMA) cement in the bone defects to induce the formation of membranes after radical debridement and reconstruction of bone defects using an autologous cancellous bone graft in a span of four to eight weeks. The purpose of this study was to explore the clinical outcomes of the induced membrane technique for the treatment of post-traumatic osteomyelitis in 32 patients. A total of 32 cases of post-traumatic osteomyelitis were admitted to our department between August 2011 and October 2012. This retrospective study included 22 men and ten women, with a mean age of 40 years (19 to 70). Within this group there were 20 tibias and 12 femurs with a mean defect of 5 cm (1.5 to 12.5). Antibiotic-loaded PMMA cement was inserted into the defects after radical debridement. After approximately eight weeks, the defects were implanted with bone graft.Objectives
Methods
Periosteum is important for bone homoeostasis
through the release of bone morphogenetic proteins (BMPs) and their
effect on osteoprogenitor cells. Smoking has an adverse effect on
fracture healing and bone regeneration. The aim of this study was
to evaluate the effect of smoking on the expression of the BMPs
of human periosteum. Real-time polymerase chain reaction was performed
for BMP-2,-4,-6,-7 gene expression in periosteal samples obtained from
45 fractured bones (19 smokers, 26 non-smokers) and 60 non-fractured
bones (21 smokers, 39 non-smokers). A hierarchical model of BMP
gene expression (BMP-2 >
BMP-6 >
BMP-4 >
BMP-7) was demonstrated
in all samples. When smokers and non-smokers were compared, a remarkable
reduction in the gene expression of BMP-2, -4 and -6 was noticed
in smokers. The comparison of fracture and non-fracture groups demonstrated
a higher gene expression of BMP-2, -4 and -7 in the non-fracture
samples. Within the subgroups (fracture and non-fracture), BMP gene
expression in smokers was either lower but without statistical significance
in the majority of BMPs, or similar to that in non-smokers with
regard to BMP-4 in fracture and BMP-7 in non-fracture samples. In
smokers, BMP gene expression of human periosteum was reduced, demonstrating
the effect of smoking at the molecular level by reduction of mRNA
transcription of periosteal BMPs. Among the BMPs studied, BMP-2
gene expression was significantly
Total knee replacement (TKR) is an effective
method of treating end-stage arthritis of the knee. It is not, however,
a procedure without risk due to a number of factors, one of which
is diabetes mellitus. The purpose of this study was to estimate
the general prevalence of diabetes in patients about to undergo
primary TKR and to determine whether diabetes mellitus adversely
affects the outcome. We conducted a systematic review and meta-analysis
according to the Meta-analysis Of Observational Studies in Epidemiology
(MOOSE) guidelines. The Odds Ratio (OR) and mean difference (MD)
were used to represent the estimate of risk of a specific outcome.
Our results showed the prevalence of diabetes mellitus among patients
undergoing TKR was 12.2%. Patients with diabetes mellitus had an increased
risk of deep infection (OR = 1.61, 95% confidence interval (CI),
1.38 to 1.88), deep vein thrombosis (in Asia, OR = 2.57, 95% CI,
1.58 to 4.20), periprosthetic fracture (OR = 1.89, 95% CI, 1.04
to 3.45), aseptic loosening (OR = 9.36, 95% CI, 4.63 to 18.90),
and a poorer Knee Society function subscore (MD = -5.86, 95% CI,
-10.27 to -1.46). Surgeons should advise patients specifically about
these increased risks when obtaining informed consent and be meticulous about
their peri-operative care. Cite this article:
Short intense electrical pulses transiently increase the permeability of the cell membrane, an effect known as electroporation. This can be combined with antiblastic drugs for ablation of tumours of the skin and subcutaneous tissue. The aim of this study was to test the efficacy of electroporation when applied to bone and to understand whether the presence of mineralised trabeculae would affect the capability of the electric field to porate the membrane of bone cells. Different levels of electrical field were applied to the femoral bone of rabbits. The field distribution and modelling were simulated by computer. Specimens of bone from treated and control rabbits were obtained for histology, histomorphometry and biomechanical testing. After seven days, the area of ablation had increased in line with the number of pulses and/or with the amplitude of the electrical field applied. The osteogenic activity in the ablated area had recovered by 30 days. Biomechanical testing showed structural integrity of the bone at both times. Electroporation using the appropriate combination of voltage and pulses induced ablation of bone cells without affecting the recovery of osteogenic activity. It can be an effective treatment in bone and when used in combination with drugs, an option for the treatment of metastases.
There are many guidelines that help direct the management of
patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken
a study to compare the management of patients with MOM hip arthroplasties in
different countries. Six international tertiary referral orthopaedic centres were
invited to participate by organising a multi-disciplinary team (MDT)
meeting, consisting of two or more revision hip arthroplasty surgeons
and a musculoskeletal radiologist. A full clinical dataset including
history, blood tests and imaging for ten patients was sent to each
unit, for discussion and treatment planning. Differences in the
interpretation of findings, management decisions and rationale for
decisions were compared using quantitative and qualitative methods.Aims
Methods
This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay.Objectives
Methods
The most frequent cause of failure after total
hip replacement in all reported arthroplasty registries is peri-prosthetic
osteolysis. Osteolysis is an active biological process initiated
in response to wear debris. The eventual response to this process
is the activation of macrophages and loss of bone. Activation of macrophages initiates a complex biological cascade
resulting in the final common pathway of an increase in osteolytic
activity. The biological initiators, mechanisms for and regulation
of this process are beginning to be understood. This article explores current
concepts in the causes of, and underlying biological mechanism resulting
in peri-prosthetic osteolysis, reviewing the current basic science
and clinical literature surrounding the topic.