The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI). This is a retrospective cohort study of operatively managed orthopaedic trauma patients from 1 January 2007 to 31 December 2016, performed in Queensland, Australia. Record linkage was used to develop a person-centric, population-based dataset incorporating routinely collected administrative, clinical, and health economic information. The FRI group consisted of patients with International Classification of Disease 10th Revision diagnosis codes for deep infection associated with an implanted device within two years following surgery, while all others were deemed not infected. Demographic and clinical variables, as well as healthcare utilization costs, were compared.Aims
Methods
There is an increasing incidence of revision for periprosthetic joint infection. The addition of vancomycin to beta-lactam antimicrobial prophylaxis in joint arthroplasty may reduce surgical site infections, however, the efficacy and safety have not been established. This was a multicenter, double-blind, superiority, placebo-controlled trial. We randomized 4239 adult patients undergoing joint arthroplasty surgery to receive 1.5g vancomycin or normal saline placebo, in addition to standard cefazolin antimicrobial prophylaxis. The primary outcome was surgical site infection at 90-days from index surgery. Perioperative carriage of In the 4113 patients included in the modified intention-to-treat population, surgical site infections occurred in 72/2069 (3.5%) in the placebo group and 91/2044 (4. 5%) in the vancomycin group (risk ratio 1.28; 95% confidence interval 0.94 to 1.73; p value 0.11). No difference was observed between the two groups for primary hip arthroplasty procedures. A higher proportion of infections occurred in knee arthroplasty patients in the vancomycin group (63/1109 [4.7%]) compared with the placebo group (42/1124 [3.7%]; risk ratio 1.52; 95% confidence interval 1.04 to 2.23; p value 0.031). Hypersensitivity reactions occurred in 11 (0.5%) patients in the placebo group and 24 (1.2%) in the vancomycin group (risk ratio 2.20; 95% confidence interval 1.08, 4.49) and acute kidney injury in 74 (3.7%) patients in the placebo group and 42 (2.1%) in the vancomycin group (risk ratio 0.57; 95% confidence interval 0.39, 0.83). Perioperative This is the first randomized controlled trial examining the addition of a glycopeptide antimicrobial to standard beta-lactam surgical antimicrobial prophylaxis in joint arthroplasty. The addition of vancomycin to standard cefazolin prophylaxis
Local antimicrobial therapy is an integral aspect of treating orthopaedic device related infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibioticloaded hydrogel in a single- stage revision for chronic methicillin-resistant sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture negative. Antibiotic delivery via hydrogel resulted in 10–100 times greater local concentrations for the first 2–3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.
To produce objective evidence that lifting is more comfortable in lumbar flexion than lumbar extension. Traditionally, lifting is taught in lumbar extension (“straight back”) but in our experience is more comfortable and stronger in flexion with backward lumbar tilt. 58 subjects performed maximal comfortable static lifts: ‘Natural’ lifting position - hip flexion, knee extension, lumbar extension Traditionally taught position - hip flexion, knee flexion, lumbar extension Backward pelvic tilt - hip flexion, knee flexion, lumbar flexion The order of these lifting methods varied to allow for variation due to fatigue/recruitment. All lifts were measured with a computerised dynamometer. The mean force for natural lifting was 13.4 kgs, for traditionally taught lifting 15.1 kgs and for backward pelvic tilt lifting 22.2 kgs This represented a 13% greater load for traditionally taught lift compared with natural lift, 66% greater for backward pelvic tilt compared with natural lift and 48% greater for backward pelvic tilt compared with traditionally taught lift.Purpose:
Method and results:
An analysis of significant neuromonitoring changes (NMCs) and evaluation of the efficacy of multimodality neuromonitoring in spinal deformity surgery. A retrospective review of prospectively collected data in 320 consecutive paediatric and adult spinal deformity operations. Patients were sub-grouped according to demographics (age, gender), diagnosis, radiographic findings (Cobb angles, MR abnormalities) and operative features (surgical approach, duration, levels of fixation). Post-operative neurological deficit was documented and defined as either spinal cord or nerve root deficit.Aim:
Method:
The risk for late periprosthetic fractures is higher in patients treated for a neck of femur fracture compared to those treated for osteoarthritis. It has been hypothesised that osteopenia and consequent decreased stiffness of the proximal femur are responsible for this. We investigated if a femoral component with a bigger body would increase the torque to failure in a biaxially loaded composite sawbone model. A biomechanical composite sawbone model was used. Two different body sizes (Exeter 44-1 vs 44-4) of a polished tapered cemented stem were implanted by an experienced surgeon, in 7 sawbones each and loaded at 40 deg/s internal rotation until failure. Torque to fracture and fracture energy were measured using a biaxial materials testing device (Instron 8874). Data are non-parametric and tested with Mann-Whitney U-test.Introduction:
Method:
In an attempt to reduce stress shielding in the proximal femur multiple new shorter stem design have become available. We investigated the load to fracture of a new polished tapered cemented short stem in comparison to the conventional polished tapered Exeter stem. A total of forty-two stems, twenty-one short stems and twenty-one conventional stems both with three different offsets were cemented in a composite sawbone model and loaded to fracture.Introduction:
Method:
The Exeter cemented polished tapered stem design was introduced into clinical practice in the early 1970's. [i] Design and cement visco-elastic properties define clinical results [ii]; a recent study by Carrington et al. reported the Exeter stem has 100% survivorship at 7 years. [iii] Exeter stems with offsets 37.5–56 mm have length 150 mm (shoulder to tip). Shorter stems, lengths 95–125 mm, exist in offsets 30–35.5 mm. The Australian National Joint Replacement Registry recently published that at 7 years the shorter stems are performing as well as longer stems on the registry [iv]. Clinical observation indicates in some cases of shorter, narrower femora that fully seating a 150 mm stem's rasp in the canal can be difficult, which may affect procedural efficiency. This study investigates the comparative risk of rasp distal contact for the Exeter 150 mm stem or a 125 mm stem. Rasps for 37.5, 44, 50 mm offset, No.1, 150 mm length stems (Exeter, Stryker Orthopaedics, Mahwah NJ) were compared with shortened length models using SOMA™ (Stryker Orthopaedics Modeling and Analytics technology). 637 patients' CT scanned femora were filtered for appropriate offset and size by measuring femoral-head to femoral-axis distance and midsection cancellous bone width (AP view). These femora were analyzed for distal contact (rasp to cortices) for 150 mm and 125 mm models (Figure 1). The widths of the rasp's distal tip and the cancellous bone boundary were compared to assess contact for each femur in the AP and ML views; the rasp was aligned along an ideal axis and flexed in order to pass through the femoral neck (ML view only).Introduction
Materials and Methods
This prospective cohort study investigated whether the use of preoperative anticoagulants is an independent risk factor for the outcomes of surgical treatment of patients with a neck of femur fracture. Data was obtained from a prospectively collected database. All patients admitted for a neck of femur fracture between Nov 2010 and Oct 2011 were included. This resulted in three hundred twenty-eight patients with 330 neck of femur fractures. Four groups were defined; patients preoperatively (i) on aspirin (n = 105); (ii) on clopidogrel (n = 28); (iii) on warfarin (n = 30); and (iv) without any anticoagulation history (n = 167, the control group). The non-warfarin group included the aspirin group, clopidogrel group and the control group. Primary outcome was the in-hospital mortality. Secondary outcomes were the postoperative complications, return to theatre and length of stay.Aim:
Methods:
There has been much discussion and controversy in the media recently regarding metal toxicity following large head metal on metal (MoM) total hip replacement (THR). Patients have been reported as having hugely elevated levels of metal ions with, at times, devastating systemic, neurolgical and/or orthopaedic sequelae. However, no direct correlation between metal ion level and severity of metallosis has yet been defined. Normative levels of metal ions in well functioning, non Cobalt-Chrome hips have also not been defined to date. The Exeter total hip replacement contains no Cobalt-Chrome (Co-Cr) as it is made entirely from stainless steel. However, small levels of these metals may be present in the modular head of the prosthesis, and their effect on metal ion levels in the well functioning patient has not been investigated. We proposed to define the “normal” levels of metal ions detected by blood test in 20 well functioning patients at a minimum 1 year post primary Exeter total hip replacement, where the patient had had only one joint replaced. Presently, accepted normal levels of blood Chromium are 10–100 nmol/L and plasma Cobalt are 0–20 nmol/L. The UK Modern Humanities Research Association (MHRA) has suggested that levels of either Cobalt or Chromium above 7 ppb (equivalent to 135 nmol/L for Chromium and 120 nmol/L for Cobalt) may be significant. Below this level it is indicated that significant soft tissue reaction and tissue damage is less likely and the risk of implant failure is reduced. Hips were a mixture of cemented and hybrid procedures performed by two experienced orthopaedic consultants. Seventy percent were female, with a mixture of head sizes used. In our cohort, there were no cases where the blood Chromium levels were above the normal range, and in more than 70% of cases, levels were below recordable levels. There were also no cases of elevated plasma Cobalt levels, and in 35% of cases, levels were negligible. We conclude that the implantation with an Exeter total hip replacement does not lead to elevation of blood metal ion levels.
Bleeding related wound complications including deep infection, superficial infection and haematoma cause significant morbidity in lower limb joint arthroplasty surgery. It has been observed anecdotally that patients requiring therapeutic anti-coagulation within the peri-operative period have higher rates of bleeding related complications and those requiring intravenous heparin particularly appear to do poorly. The aim of this study is to investigate the relationship between post-operative bleeding and wound complications in the patient requiring therapeutic warfarin, plus or minus heparin, in total hip arthroplasty surgery. This is a retrospective cohort study reviewing 1047 primary total hip replacements performed in a single centre over a five year period and comparing outcomes of the patients on warfarin (89) with a double-matched control group of patients not on warfarin (179). Outcomes included rates of deep infection, excessive wound ooze or haematoma, superficial infection, return to OT for washout and need for revision operation. The study group was then sub analysed comparing those on IV heparin plus oral warfarin, to those on warfarin alone. The warfarin group had significantly higher risk of deep joint infection (9% vs 2.2% p= 0.023), haematoma/wound ooze (28% vs 4% p < 0.001) and superficial infection (13.5% vs 2.2% p < 0.001) compared to the control group. In the sub analysis of the study group, those on IV heparin had significantly higher risk of haematoma/wound ooze (44% vs 28% p= 0.023) than those on warfarin alone. The requirement of therapeutic anti-coagulation in the peri-operative period is a tenuous balance between the complications of thrombo-embolic disease and bleeding-related morbidity. In the past, perhaps the full burden of bleeding related complications has not been appreciated, but now improved understanding will enable the both the surgeon and the patient to make more informed decisions regarding therapeutic anticoagulation in elective arthroplasty surgery.
Favourable long-term results have been reported with the standard Exeter cemented stem. We report our experience with a version for use in smaller femora, the Exeter 35.5 mm stem. Although, also a collarless polished taper, the stem is slimmer and 25 mm shorter than a standard stem. Between August 1988 and August 2003, 192 primary hip arthroplasties were performed in 165 patients using the Exeter 35.5 mm stem. Clinical and operative data were collected prospectively. Clinical evaluation was by the Charnley, Harris and Oxford hip scores and radiographs were analysed post-operatively and at latest follow up. The mean age at time of operation was 53 years (18 to 86), with 73 patients under the age of 50 years. The diagnosis was osteoarthritis in 91, hip dysplasia in 77, inflammatory arthritis in 18, septic arthritis of the hip in three, secondary to Perthes disease in two and avascular necrosis of the hip in one patient. The fate of every implant is known. At a median follow-up of 8 years (5 to 19), survivorship with revision of the femoral stem for aseptic loosening as the endpoint was 100%. Fifteen cases (7.8%) underwent further surgery 11 for acetabular revision, one for stem fracture and three others. Although, smaller than a standard Exeter Universal polished tapered cemented stem—with a shorter, slimmer taper—the performance of the Exeter 35.5 mm stem was equally good even in this young, diverse group of patients.
Impaction bone grafting (IBG) of the acetabulum in cemented primary total hip replacement is a useful technique in the management of acetabular deficiencies. It has the capacity to restore anatomy and bone stock with good long-term outcome. We present 125 consecutive cases of IBG with a cemented polyethylene component. All patients who received full IBG of the acetabulum in primary cemented Exeter total hip replacements and who underwent surgery between August 1995 and August 2003 were identified. All operative and follow-up data was collected prospectively and no patients were lost to follow-up. All patients underwent pre-operative and regular post-operative hip scores with the Harris, Oxford and the modified Charnley scoring systems. Data on indication, surgical technique, socket position and migration and revision was reviewed at a mean follow-up of 7.6 (range 5 to13.4) years. Between August 1995 and August 2003, 113 patients (85 females) with an average age of 67.8 (range 22.9–99.2) years underwent 125 primary Exeter cemented total hip replacements with IBG of acetabular defects. Acetabular defects were classified according to the AAOS classification as cavitatory in 62 hips and as segmental, requiring application of a rim mesh prior to IBG, in 63 hips. Life tables were constructed demonstrating 86.4% survival of the acetabular component at 13.4 years with revision for any reason as the endpoint and 89.3% survival with revision for aseptic loosening as the endpoint. Of the seven patients who underwent revision for aseptic loosening, all had pre-operative segmental acetabular defects requiring application of a rim mesh. No patient who underwent IBG for a cavitatory defect required revision surgery for aseptic loosening. Survival of the Exeter cemented femoral component was 100% at 13.4 years with revision for aseptic loosening as the endpoint. There were 11 radiographic failures of the acetabular component, which have not been revised at latest review. One of these is symptomatic but not fit for revision surgery, two were asymptomatic at time of death and eight are asymptomatic but under review. This is the largest series of IBG in the acetabulum in cemented primary THR. Our results suggest that the medium term survival of this technique is good, particularly when used for cavitatory defects. Although there were radiographic failures, these are largely asymptomatic and may not require revision.
The cement in cement technique for revision total hip arthroplasty (THA) has shown good results in selected cases. However, results of its use in the revision of hemiarthroplasty to THA has not been previously reported. Between May 1994 and May 2007 28 (20 Thompson's and 8 Exeter bipolar) hip hemiarthroplasties were revised to THA in 28 patients using the cement in cement technique. All had an Exeter stem inserted at the time of revision. Clinical and operative data were collected prospectively. Clinical evaluation was by the Charnley, Harris and Oxford. Hip scores and radiographs were analysed post-operatively and at latest follow up. The mean age at time of hemiarthroplasty revision was 80 (35 to 93) years. The reason for revision was acetabular erosion in 12 (43%), recurrent dislocation in eight (29%), aseptic stem loosening in four (14%), periprosthetic fracture in two (7%) and infection in a further two (7%) patients. No patient has been lost to follow up. Three patients died within three months of surgery. The mean follow up of the remainder was 50 (16 to 119) months. Survivorship with revision of the femoral stem for aseptic loosening as the endpoint was 100%. Three cases (11%) have since undergone further revision, one for recurrent dislocation, one for infection, and one for periprosthetic fracture. The cement in cement technique can be successfully applied to revision of hip hemiarthroplasty to THA. It has a number of advantages in this elderly population including minimising bone loss, blood loss and operative time.
Removal of well-fixed cement at the time of revision THA for sepsis is time consuming and risks bone stock loss, femoral perforation or fracture. We report our experience of two-stage revision for infection in a series of cases in which we have retained well-fixed femoral cement. All patients underwent two-stage revision for infection. At the first stage the prostheses and acetabular cement were removed but when the femoral cement mantle demonstrated good osseo-integration it was left in-situ. Following Girdlestone excision arthroplasty (GEA), patients received local antibiotics delivered by cement spacers, as well as systemic antibiotics. At the second stage the existing cement mantle was reamed, washed and dried and then a femoral component was cemented into the old mantle. Sixteen patients (M:F 5:11) had at least three years follow-up (mean 80 months – range 43 to 91). One patient died of an unrelated cause at 53 months. Recurrence of infection was not suspected in this case. The mean time to first stage revision was 57 months (3 to 155). The mean time between first and second stages was nine months (1 to 35). Organisms were identified in 14 (87.5%) cases (5 Staphylococcus Aureas, 4 Group B Streptococcus, 2 Coagulase negative Staphylococcus, 2 Enterococcus Faecalis, 1 Escheria Coli). At second stage, five (31.2%) acetabulae were uncemented and 11 (68.8%) were cemented. There were two complications; one patient dislocated 41 days post-operatively and a second patient required an acetabular revision at 44 days for failure of fixation. No evidence of infection was found at re-revision. One patient (1/16, 7%) has been re-revised for recurrent infection. Currently no other patients are suspected of having a recurrence of infection (93%). Retention of a well-fixed femoral cement mantle during two-stage revision for infection and subsequent cement-in-cement reconstruction appears safe with a success rate of 93%. Advantages include a shorter operating time, reduced loss of bone stock, improved component fixation and a technically easier second stage procedure.
Surgery for degenerative lumbar spondylolisthesis may entail both decompression and fusion. The knee-chest position facilitates the decompression, but fixation in this position risks fusion in kyphosis. This can be avoided by intra-operative re-positioning to the prone position. The aim of this study was to quantify the restoration of lordosis achieved by intra-operative repositioning and to assess the clinical and radiological outcome. A total of forty consecutive patients with degenerative lumbar spondylolisthesis and stenosis were treated by posterior decompression and interbody fusion with pedicle screw fixation. The screw insertion, decompression and interbody grafting were performed with the patient in the knee-chest position. The patient was then re-positioned to the fully prone position for fusion. Sagittal plane angles were measured pre-, intra- and post-operatively. Clinical assessment was performed using SF-36 scores and visual analogue scores for back and leg pain. The sagittal plane angle increased from median 16.0 degrees pre-operatively to 23.1 degrees post-operatively (p<0.01) and this was maintained at the last follow-up (mean 21 months). The SF-36 scores improved for 7 out of 8 domains and the physical score improved from 29% to 40% (p<0.05). The mean pain scores improved significantly from 7.5 to 3.8 for back pain and from 7.6 to 3.7 for leg pain (p<0.001). Lumbar spondylolisthesis was found to be associated with a reduction of normal lumbar lordosis and the knee-chest position exacerbates this loss of lordosis. Intra-operative repositioning restored lordosis to greater than the pre-operative angle and was associated with a good clinical outcome.
Data from recent AOANJRR shows a higher incidence of acetabular revision for dislocation of THA in uncemented compared to cemented THA (RR 1.59). We hypothesized that a difference in accuracy of component placement may be a factor. We aimed to assess any difference in accuracy between these 2 types of THA. Patients undergoing navigated THA were prospectively recruited. Choice of uncemented or cemented THA was based on individual surgeon’s routine practice and preference and no adjustments were made for this study. All THAs (Cemented Exeter-21 and uncemented Trident/Secur fit-20) were performed through a posterior approach. Statistical analysis: the mean and 95% confidence intervals (or median and interquartile range (IQR) for non parametric data) for each measure in both groups. ANOVA and nonparametric Mann-Whitney U test (significance level 5%). Levene’s test for homogeneity, Comparison of frequencies with chi-squared test or Fishers Exact test. Bonferroni correction where necessary. We demonstrated a significant difference in reproducibility between components. Four of 20 (20%) uncemented cups deviated from the target inclination by 5 degrees or more compared to none of 21 in the cemented group (p=0.048). Seven of the 20 (35%) of the uncemented cups deviated from the target version by 5 degrees or more compared to none of 21 in the cemented group (p=0.003). There was a significant difference between the groups with regard to deviation from planned leg length (p<
0.001). Deviation from target leg length of greater than 5mm was found in 36.4% of the uncemented cases as compared to 8.3% of the cemented cases although due to the small numbers this was not statistically significant (p=0.16). Statistically significant reduced accuracy of cup placement is demonstrated with uncemented compared to cemented implants. It is harder to control implant positioning in uncemented implants than cemented implants.
Less blood loss and operative times were found with skip laminectomy. Similar degrees of decompression with both techniques. Significantly improved axial pain scores with skip laminectomy. Significantly improved preservation of range of movement with skip laminectomy.
Tissue engineering is a rapidly expanding field of research. Bone and cartilage engineering are being undertaken in an attempt to treat osteoarthritis and repair bone defects. In spite of extensive research little successful clinical application of this work has been seen. There are however many advances in the field that one day may have therapeutic interest. One particular area of interest is the potential for using osteophyte tissue in repairing osteoarthritic defects. Osteophytes represent an attempt by the body to regenerate bone and cartilage. They present an obvious source of cells for tissue engineering. Research ay QUT has shown that cells within the osteophytes are a better source of bone and cartilage regeneration in the laboratory than matched patient’s bone marrow stem cells. Osteoarthritis remains the ultimate challenge for orthopaedic tissue engineering. Understanding the chemical and mechanical signals occurring in osteoarthritis presents opportunities for targeted drug delivery and potential slowing of disease. We have identified changes within the MMP profile of cells at the osteochondral junction. Subchondral sclerosis appears to be associated with changes in the nature of chondrocytes deep within the cartilage layer. This transformation of chondrocytes into osteoblast-like tissue in many ways mimics the changes seen in the growth plate once maturity is reached. Understanding the parallels between these processes may help answer some of the mechanisms of the development of osteoarthritis. This talk will discuss the above topics as well as other areas of interest to an orthopaedic surgeon working within a group of 10 cell biologists.
This presentation introduces a new tool to be used in the cementing of acetabular components in total hip arthroplasty, the ‘Rim Cutter’. The Rim Cutter is designed to cut a ledge in the rim of the acetabulum into which a flanged cup can be cemented. The flange is trimmed such that it fits precisely into the ledge cut in the acetabulum. We present the in vitro pilot study of the effect of using this tool on the intra-acetabular cement mantle pressure during cup insertion and also the effect on the depth of cement penetration as the cup is inserted. A significant improvement in both cement pressure and cement penetration over conventional flanged and unflanged cups is noted. Improved cement penetration around the rim of the acetabulum in THR has implications for reducing the rate of aseptic loosening. The pilot study also suggests other beneficial features of using the rim cutter such as improved cup centralisation, control of orientation and the prevention of the cup ‘bottoming out’. Further in vivo studies are required to better assess its efficacy.
To regenerate the complex tissue such as bone-cartilage construct using tissue engineering approaches, controllable differentiation of mesenchymal stem cells (BMSCs) into chondrogenic and osteogenic lineages is crucially important. Although bilayered scaffolds have been investigated in vitro and in vivo, no culture system is available to test BMSCs differentiation into bone and cartilage simultaneously in bilayered scaffolds. This study investigated a defined culture media, which supported osteoblast and chondrocyte differentiation depending on growth factors implemented in biomaterials. In 2-dimensional culture, BMSCs differentiated to chondrocytes when transforming growth factor-beta 3 (TGF-β3) was added to the defined media, whereas osteogenic differentiation was induced by adding bone morphogenetic protein 7 (BMP-7). BMSC differentiation to osteogenic and chondrogenic lineages was further strengthen in 3-dimensional culture. Proteoglycan formation, type II collagen, and aggrecan were upregulated in the defined media when BMSCs were mixed with fibrin gel impregnated with TGF-β3. Mineralization and the expression of osteogenic markers such as alkaline phosphatase, osteopontin, and osteoclacin were noticeable when BMSCs cultured in hydroxyapatite-tricalcium phosphate (HA/TCP) scaffolds coated with BMP-7. This study generated and tested a growth media, which could induce osteogenic and chondrogenic differentiation of BMSCs in one culture system. These results will help the development of tissue substitutes for multi-complexed tissues such as subchondral replacement.
Bone Tissue Engineering Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia Adult mesenchymal stem cells (MSCs) are a topic of immense research interest in the field of tissue engineering. Since, depletion of multipotent cells has been implicated in degenerative joint diseases, cell based therapies have been proposed for tissue regeneration, especially for cartilage repair. The aim of the present study is to focus on the possibility of deriving and expanding multipotential MSCs from the heterogeneous bone marrow stromal samples of patients with osteoarthritis (OA) by characterising MSCs at the single cell level. Single cell clonal cultures were established by limiting dilution of marrow stromal cells from three OA patients. A total of 14 clones with a wide variation in their cell doubling time were isolated. The clones were grouped into fast-growing and slow-growing clones. All except one of the fast-growing clones were tripotential. However the slow-growing clones showed limited differentiation potential and morphological changes associated with cellular senescence with extended duration in culture. Flow cytometric analysis did not depict any difference in the expression of the selected putative MSC cell surface markers CD29, CD44, CD90, CD105 and CD166 between fast-growing and slow-growing clones indicating a strong need to investigate for novel cell-surface markers. Further, proteomic analysis to understand the sub-cellular processes responsible for the existence of varying sub-populations identified 11 differentially expressed proteins. These proteins were reported to be associated with cellular organization, signal transduction, energy pathways and stress related proteins. Identification of signaling pathway proteins and cell cycle related proteins, such as calmodulin and caldesmon in the clonal populations, suggest that high-throughput proteomic technologies like two dimensional liquid chromatography (2D LC) coupled with mass spectrometry (MS) may facilitate the discovery of therapeutically useful biomarkers. This study demonstrated the existence of a fast-growing multipotential MSC population from bone marrow samples of patients with OA. Therefore, despite a supposedly smaller stem cell compartment in these patients, we demonstrate here that they can still yield a potentially therapeutically useful source of syngeneic MSCs.
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.
In both physiological and pathological processes, periosteum plays a determinant role in both bone formation and fracture healing. However, no specific reports are available so far focusing on the detailed structural and major cellular differences between the periostea covering different bone surface areas in relation to ageing. The aim of this study is to compare the structural and cellular differences in diaphyseal and epiphyseal periostea in different-aged rats using histological and immunohistochemical methods. Four female Lewis rats from each group of juvenile (7-week old), mature (7-month old) and aged groups (2-year old) were sacrificed and the right femur of each rat was retrieved, fixed, decalcified and embedded. 5μm thick serial sagittal sections were cut and stained with Hematoxylin and Eosin, Stro-1 (stem cell marker), F4/80 (macrophage marker), TRAP (osteoclast marker) and vWF (endothelial cell marker). 1mm length of middle diaphyseal and epiphyseal periosteum were selected for observation. The thickness, total cell number and positive cell number for each antibody in each periosteal area and different-aged groups were measured and compared. The results were subjected to ANOVA and SNK-q tests. The results showed that the thickness and cell number in diaphyseal periosteum decreased with age (p<
0.001). In comparison with diaphyseal area, the thickness and cell number in epiphyseal periosteum were much higher (p<
0.001). There were no significant differences between the juvenile and aged groups in the thickness and cell number in cambial layer of epiphyseal periosteum (p>
0.05). However, the juvenile rats had more Stro1+, F4/80+ cells and blood vessels and few TRAP+ cells in different periosteal areas compared with other groups(p<
0.001). The aged rats showed much less Stro1+ cells, but more F4/80+,TRAP+ cells and blood vessels in the cambial layer of epiphyseal periosteum (p<
0.001). In conclusion, the age-related structure and cell population in diaphyseal and epiphyseal periostea are different, especially in aged rats. The epiphyseal periosteum of aged rats seems more destructive than diaphyseal part and other age groups. Macrophages in the periosteum play a dual important role in osteogenesis and osteoclastogenesis.
Bone Tissue Engineering Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia. Osteophytes are the most remarkable and consistently distinct feature of osteoarthritis (OA). Their formation may be related to pluripotential cells in the periosteum responding to stimulus during OA. This study aimed to isolate stem cells from osteophyte tissues, and characterise their phenotype, proliferation and differentiation potential, and immuno-modulatory properties. Osteophyte derived cells were isolated from five osteophyte tissue samples collected during knee replacement surgery. These cells were characterised by the expression of cell surface antigens, differentiation potential into mesenchymal lineages, growth kinetics and modulation of allo-immune responses. Multipotential stem cells (MSCs) were identified from all osteophyte samples namely osteophyte derived MSCs (oMSCs). The surface antigen expression of oMSCs was consistent with that of mesenchymal stem cells, such as lacking the haematopoietic and common leukocyte markers (CD34, CD45) while expressing those related to adhesion (CD29, CD166, CD44) and stem cells (CD90, CD105, CD73). The longevity of oMSCs in culture was superior to that of bone marrow derived MSC (bMSCs), and they readily differentiated into tissues of the mesenchymal lineages. oMSCs also demonstrated the ability to suppress allogeneic T-cell proliferation, which was associated with the expression of tryptophan degrading enzyme indoleamine 2,3 dioxygenase (IDO). Our results showed that osteophyte derived cells had similar properties to mesenchymal stem cells in the expression of antigen phenotype, differential potential and suppression of allo-immune response. Furthermore, when compared to bMSCs, oMSCs maintained a higher proliferative capacity, which may offer an alternative source for therapeutic stem cell based tissue regeneration.
We are comparing the above two techniques with 25 patients in each group operated by 3 surgeons. The first group had conventional laminoplasty and the second group underwent the skip laminectomy. The groups were comparable in age, sex, pathology and clinical presentation. Both these group had clinical outcome measurements using SF 12 questionnaires, pre and postoperative clinical assessment with standard tools performed by independent surgeon and a specialist spinal physiotherapist. We also routinely performed pre and postoperative MRI scans to assess the adequacy of decompression.
58,109 primary hip replacements for osteoarthritis were investigated for effect of age group, sex and fixation method. Age group and sex were not significant risk factors in revision for dislocation. Studying fixation method, cementless acetabular components were implanted more frequently (49,027, 84%) than cemented (9,082, 15.6%). In total, there were 428 (0.7%) revisions for dislocation, 369(0.8%) with a cementless acetabulum and 59 (0.6%) with cemented. Relative risk (cementless v cemented acetabulum adjusted for age group, sex and head size) of 1.59 (CI 1.19 to 2.12, p<
0.01). Head sizes of >
30mm, 28mm, 26mm and 22mm had significantly increasing relative risk (p<
0.001).
There was no significant correlation between clinical leg length change, measured in the operating theatre and the leg length change predicted by navigation. Accuracy of cup and stem placement was assessed by comparison of the homogeneity of variances, the Levene statistic, in the navigated and control groups. The range of cup inclination, cup version and stem version was significantly narrowed in the navigation group (p<
0.05).
We are comparing the above two techniques with 25 patients in each group operated by 3 surgeons. The first group had conventional laminoplasty and the second group underwent the skip laminectomy. The groups were comparable in age, sex, pathology and clinical presentation. Both these group had clinical outcome measurements using SF 12 questionnaires, pre and postoperative clinical assessment with standard tools performed by independent surgeon and a specialist spinal physiotherapist. We also routinely performed pre and postoperative MRI scans to assess the adequacy of decompression.
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).
Computer aided joint replacement surgery has become very popular during recent years and is being done in increasing numbers all over the world. The accuracy of the system depends to a major extent, on accurate registration and immobility of the tracker attachment devices to the bone. This study was designed to assess the forces needed to displace the tracker attachment devices in the bone simulators. Bone simulators were used to maintain the uniformity of the bone structure during the study. The fixation devices tested were 3mm diameter self drilling, self tapping threaded pin, 4mm diameter self tapping cortical threaded pin, 5mm diameter self tapping cancellous threaded pin and a triplanar fixation device ‘ortholock’ used with three 3mm pins. All the devices were tested for pull out, translational and rotational forces in unicortical and bicortical fixation modes. Also tested was the normal bang strength and forces generated by leaning on the devices. The forces required to produce translation increased with the increasing diameter of the pins. These were 105 N, 185 N, and 225 N for the unicortical fixations and 130N, 200N, 225 N for the bicortical fixations for 3mm, 4mm and 5 mm diameter pins respectively. The forces required to pull out the pins were 1475N, 1650N, 2050N for the unicortical, 1020N, 3044N and 3042N for the bicortical fixated 3mm, 4mm and 5mm diameter pins. The ortholock translational and pull out strength was tested to 900N and 920N respectively and still it did not fail. Rotatory forces required to displace the tracker on pins was to the magnitude of 30N before failure. The ortholock device had rotational forces applied up to 135N and still did not fail. The manual leaning forces and the sudden bang forces generated were of the magnitude of 210 N and 150 N respectively. The strength of the fixation pins increases with increasing diameter from three to five mm for the translational forces. There is no significant difference in pull out forces of four mm and five mm diameter pins though it is more than the three mm diameter pins. This is because of the failure of material at that stage rather than the fixation device. The rotatory forces required to displace the tracker are very small and much less than that can be produced by the accidental leaning or bang produced by the surgeon or assistants in single pins. Although the ortholock device was tested to 135 N in rotation without failing, one has to be very careful not to put any forces during the operation on the tracker devices to ensure the accuracy of the procedure.
Urist performed a similar series of experiments in guinea pigs as Huggins did in his canine model. After two weeks, mesenchymal cells condensed against the columnar epithelium and membranous bone with haversian systems and marrow began to form juxtapose the basement membrane. At no time was cartilage formation noted, only direct membranous bone formation. They also demonstrated the expression of BMP’s in migrating epithelium and suggested that BMP is the osteoinductive factor in heterotopic bone formation.
In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a commercial source.