Even Experts Can Be Fooled: Reliability of Clinical Examination for Diagnosing Hip Dislocations in Newborns.

BACKGROUND: The aim of this study was to assess the accuracy of clinical screening examination in newborns with dislocated hips compared with ultrasound scan (USS). METHODS: Newborns, up to 3 months of age, with confirmed hip dislocations on USS were prospectively enrolled in a multinational observational study. Data from 2010 to 2016 were reviewed to determine pretreatment clinical examination findings of the treating orthopaedic surgeon as well as baseline ultrasound indices of developmental dysplasia of the hip (DDH). All infants had been referred to specialist centres with expertise in DDH, due to abnormal birth examination or risk factor. RESULTS: The median age of the study population was 2.3 weeks and 84% of patients were female. Of the total 515 USS-confirmed dislocated hips included in the study, 71 (13.8%) were incorrectly felt to be reduced on clinical examination by the treating orthopaedist (P<0.001). Full hip abduction was documented in 106 hips. Of the hips correctly identified as dislocated, 322 hips were further analyzed based on clinical reducibility. Thirty-three of 322 (10.2%) were incorrectly thought to be reducible when in fact they were irreducible or vice versa. CONCLUSIONS: Expert examiners missed a significant number of frankly dislocated hips on clinical examination and their ability to classify hips based on clinical reducibility was only moderately accurate. This study provides evidence that, even in experienced hands, physical examination findings in DDH are often too subtle to elicit clinically in the first few months of life. This may explain the persistent and measurable rate of late presenting dislocations in countries with screening programmes reliant on clinical examination. LEVEL OF EVIDENCE: Level 1-testing of previously developed diagnostic criteria in series of consecutive patients (with universally applied reference "gold" standard).

Preoperative Gallows traction as an adjunct to hip open reduction surgery: Is it safe and is it effective?

Background: Traction is used at our hospital before open reduction in infants with developmental dysplasia of the hip. Theoretically, it reduces soft-tissue tension, allowing an easier surgical reduction and therefore lower surgical complications. Owing to extended hospital stays, potential complications, and lack of evidence, the use of traction has decreased. This study aims to quantify whether traction is safe and whether it has any demonstrable effect. Methods: The perioperative course of 80 patients undergoing preoperative traction and hip open reduction were reviewed. The height of hip dislocation was classified using the International Hip Dysplasia Institute classification system on both radiographs taken before and after traction. Any complications related to traction were recorded, along with the requirement for femoral shortening osteotomies, incidence of re-dislocation, and longer-term rate of avascular necrosis. Results: Traction lowered the resting position of the majority of hips, with the median International Hip Dysplasia Institute grade before traction improving from 4 to 3, a statistically significant improvement (p < 0.00001). There were no neurovascular complications. Two babies were complicated with broken skin sores; however, surgery still progressed uneventfully. Zero hips in the cohort required femoral shortening osteotomies to achieve a tension-free reduction, and the re-dislocation rate was 0%. However, 96% of hips were Severin 1 or 2 at 6-year follow-up. Conclusion: Notably, 1 week of preoperative traction significantly improves the resting position of the hip in high dislocations. It is safe when used in infants weighing <12 kg, and subsequent surgical outcomes are excellent, thus supporting its use ahead of developmental dysplasia of the hip open reduction surgery. Level of evidence: Level IV.

Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration.

BACKGROUND: Recent approaches have sought to harness the potential of stem cells to regenerate bone that is lost as a consequence of trauma or disease. Bone marrow aspirate (BMA) provides an autologous source of osteoprogenitors for such applications. However, previous studies indicated that the concentration of osteoprogenitors present in BMA is less than required for robust bone regeneration. We provide further evidence for the importance of BMA enrichment for skeletal tissue engineering strategies using a novel acoustic wave-facilitated filtration strategy to concentrate BMA for osteoprogenitors, clinically applicable for intraoperative orthopedic use. METHODS: Femoral BMA from 15 patients of an elderly cohort was concentrated for the nucleated cell fraction against erythrocytes and excess plasma volume via size exclusion filtration facilitated by acoustic agitation. The effect of aspirate concentration was assessed by assays for colony formation, flow cytometry, multilineage differentiation and scaffold seeding efficiency. RESULTS: BMA was filtered to achieve a mean 4.2-fold reduction in volume with a corresponding enrichment of viable and functional osteoprogenitors, indicated by flow cytometry and assays for colony formation. Enhanced osteogenic and chondrogenic differentiation was observed using concentrated aspirate and enhanced cell-seeding efficiency onto allogeneic bone graft as an effect of osteoprogenitor concentration relative specifically to the concentration of erythrocytes in the aspirate. CONCLUSIONS: These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing.

The management of developmental dysplasia of the hip in children aged under three months : a consensus study from the British Society for Children's Orthopaedic Surgery.

AIMS: A national screening programme has existed in the UK for the diagnosis of developmental dysplasia of the hip (DDH) since 1969. However, every aspect of screening and treatment remains controversial. Screening programmes throughout the world vary enormously, and in the UK there is significant variation in screening practice and treatment pathways. We report the results of an attempt by the British Society for Children's Orthopaedic Surgery (BSCOS) to identify a nationwide consensus for the management of DDH in order to unify treatment and suggest an approach for screening. METHODS: A Delphi consensus study was performed among the membership of BSCOS. Statements were generated by a steering group regarding aspects of the management of DDH in children aged under three months, namely screening and surveillance (15 questions), the technique of ultrasound scanning (eight questions), the initiation of treatment (19 questions), care during treatment with a splint (ten questions), and on quality, governance, and research (eight questions). A two-round Delphi process was used and a consensus document was produced at the final meeting of the steering group. RESULTS: A total of 60 statements were graded by 128 clinicians in the first round and 132 in the second round. Consensus was reached on 30 out of 60 statements in the first round and an additional 12 in the seond. This was summarized in a consensus statement and distilled into a flowchart to guide clinical practice. CONCLUSION: We identified agreement in an area of medicine that has a long history of controversy and varied practice. None of the areas of consensus are based on high-quality evidence. This document is thus a framework to guide clinical practice and on which high-quality clinical trials can be developed.Cite this article: Bone Joint J 2023;105-B(2):209-214.

The Free-Gliding screw for slipped capital femoral epiphysis : is it safe, does it glide, and does age matter?

AIMS: Fixation techniques used in the treatment of slipped capital femoral epiphysis (SCFE) that allow continued growth of the femoral neck, rather than inducing epiphyseal fusion in situ, have the advantage of allowing remodelling of the deformity. The aims of this study were threefold: to assess whether the Free-Gliding (FG) SCFE screw prevents further slip; to establish whether, in practice, it enables lengthening and gliding; and to determine whether the age of the patient influences the extent of glide. METHODS: All patients with SCFE who underwent fixation using FG SCFE screws after its introduction at our institution, with minimum three years' follow-up, were reviewed retrospectively as part of ongoing governance. All pre- and postoperative radiographs were evaluated. The demographics of the patients, the grade of slip, the extent of lengthening of the barrel of the screw and the restoration of Klein's line were recorded. Subanalysis was performed according to sex and age. RESULTS: A total of 19 hips in 13 patients were included. The mean age of the patients at the time of surgery was 11.5 years (9 to 13) and the mean follow-up was 63 months (45 to 83). A total of 13 FG SCFE screws were used for the fixation of mild or moderate SCFE, with six contralateral prophylactic fixations. No hip with SCFE showed a further slip after fixation and there were no complications. Lengthening occurred in 15 hips (79%), with a mean lengthening of the barrel of 6.8 mm (2.5 to 13.6) at final follow-up. Remodelling occurred in all hips with lengthening of the barrel. There was statistically more lengthening in patients who were aged < 12 years, regardless of sex (p = 0.002). CONCLUSION: The FG SCFE screw is effective in preventing further slip in patients with SCFE. Lengthening of the barrel occurred in most hips, and thus allowed remodelling. This was most marked in younger children, regardless of sex. Based on this study, this device should be considered for use in patients with SCFE aged < 12 years instead of standard pinning in situ.Cite this article: Bone Joint J 2023;105-B(2):215-219.

An Explorative Study into the Aetiology of Developmental Dysplasia of the Hip Using Targeted Urine Metabolomics.

Developmental dysplasia of the hip (DDH) is the most prevalent congenital musculoskeletal disorder, yet its cause remains unknown. Adequate nutrient provision and coordinated electron exchange (redox) processes are critical for foetal growth and tissue development. This novel study sought to explore specific biochemical pathways in skeletal development for potential involvement in the aetiology of DDH. Spot urine samples were collected from infants, aged 13-61 days, with and without DDH. Ion chromatography-mass spectrometry was used to quantify thiosulphate, sulphate, nitrate, and phosphate, whilst nitrite was quantified using high-performance liquid chromato-graphy. Thiobarbituric acid reactive substances (TBARS) were measured as markers of lipid peroxidation. Creatinine and osmolality were determined by a 96-well plate assay and micro-osmometer to potentially normalise values for renal function, lean body mass, and hydration status. Urine samples were analysed from 99 babies: 30 with DDH and 69 age-matched non-DDH controls. Thiosulphate, TBARS, and creatinine concentrations differed between the DDH group and the controls (p = 0.025, 0.015, and 0.004 respectively). Urine osmolality was significantly lower in DDH compared to the controls (p = 0.036), indicative of the production of a more diluted urine in DDH infants. Following adjustment for osmolality, significant differences became apparent in urinary sulphate levels in DDH (p = 0.035) whereas all other parameters were similar between the groups. This is the first study to assess the potential role of these inorganic anions in DDH. The higher levels of sulphate found in infants with DDH suggests either enhanced intake from milk, increased endogenous formation, or impaired renal reabsorption. This investigation demonstrates the power of urine metabolomics and highlights the importance of normalisation for hydration status to disentangle developmental disorders. Our results strongly suggest that DDH is a systemic disease associated with altered uptake, formation, or handling of sulphate. There is potential for new opportunities in the prevention or treatment of DDH via nutritional intervention.

Cost Analysis of Screening Programmes for Developmental Dysplasia of the Hip: A Systematic Review.

AIMS: The aim of this study was to assess screening costs in developmental dysplasia of the hip (DDH), to provide any clarity on the cost-effectiveness of various hip screening programmes internationally. METHODS: A PROSPERO-registered systematic review was performed by examining cost analysis studies of various DDH screening programmes, including those based around clinical examination, selective ultrasound and universal ultrasound. Costs were analysed using narrative synthesis. RESULTS: There were 14 studies included in this review. Two studies found that clinical hip screening is advantageous over no screening at all, both in terms of overall cost and favourable outcomes. When considering selective ultrasound imaging versus clinical screening, two studies found it to be more expensive, one found it cheaper and three studies calculated the overall programme costs to be similar. With universal ultrasound, four studies calculated this to be cheaper than clinical or selective ultrasound screening due to a reduced late detection and surgery rate. However, a comparable number of studies concluded that the increased financial costs of universal ultrasound were greater than the reduction in surgical costs. No studies included any long-term data. CONCLUSION: There is a dearth of information on DDH screening costs, with significant heterogeneity amongst the existing literature. Future research should include the cost analysis of long-term complications of DDH, including the social and psychological impact of early onset arthritis, as well as gender specific ultrasound screening programmes.

There is No Link Between Birth Weight and Developmental Dysplasia of the Hip.

AIMS: Developmental Dysplasia of the Hip (DDH) has been linked to high birth weight and packaging disorders, though the evidence is limited. This has implications on screening strategies. The aim of this study was to establish whether birth weight was truly associated with the incidence of DDH. PATIENTS AND METHODS: This cohort study analysed the birth weights of all babies born at our institution over a 24 month period, between 01/01/2017 and 01/01/2019. Babies with DDH and those without DDH were compared. Babies were excluded if born before 38 weeks, had incomplete data or were a non-singleton pregnancy. Sub-analysis was performed for DDH severity (dysplastic versus subluxed/dislocated hips), breech presentation, gestational age, gender and ethnicity. Statistical analysis was performed using SPSS. RESULTS: There were 10,113 babies born at our institution during the selected timeframe, of which 884 were excluded for prematurity, 336 for being non-singleton and 19 for incomplete data. This left 8874 for analysis, of which 95 babies had confirmed DDH. Both the Non-DDH and DDH data sets had normal distribution (Shapiro-Wilkes, p = 0.308 and 0.629, respectively), with mean birth weights of 3477.7 g with DDH and 3492.8 g without DDH. No difference in birth weight was found (Independent T test, p = 0.789). Females had a lower birth weight than males (3293.1 g versus 3416.6 g (p < 0.001)) yet have a higher incidence of DDH (ratio 6:1 in this dataset). No significant difference was found between birth weights of females with and without DDH (p = 0.068), nor between males with and without DDH (p = 0.513). There were no significant differences in birth weights even when only displaced hips were analysed (p = 0.543), nor according to breech presentation (p = 0.8). Longer gestation babies weighed more (p < 0.00001), yet showed no increase in DDH incidence (p = 0.64). CONCLUSION: This study discredits the belief that DDH may be related to higher birth weight, thus casting doubt on the link to DDH being a packaging problem in utero. This, therefore, allows future research to prioritise the investigation of alternative aetiologies.

Dynamic deformation of the femoral head occurs on weightbearing in Legg-Calves-Perthes disease: a translational pilot study.

AIMS: Though the pathogenesis of Legg-Calve-Perthes disease (LCPD) is unknown, repetitive microtrauma resulting in deformity has been postulated. The purpose of this study is to trial a novel upright MRI scanner, to determine whether any deformation occurs in femoral heads affected by LCPD with weightbearing. METHODS: Children affected by LCPD were recruited for analysis. Children received both standing weightbearing and supine scans in the MROpen upright MRI scanner, for coronal T1 GFE sequences, both hips in field of view. Parameters of femoral head height, width, and lateral extrusion of affected and unaffected hips were assessed by two independent raters, repeated at a one month interval. Inter- and intraclass correlation coefficients were determined. Standing and supine measurements were compared for each femoral head. RESULTS: Following rigorous protocol development in healthy age-matched volunteers, successful scanning was performed in 11 LCPD-affected hips in nine children, with seven unaffected hips therefore available for comparison. Five hips were in early stage (1 and 2) and six were in late stage (3 and 4). The mean age was 5.3 years. All hips in early-stage LCPD demonstrated dynamic deformity on weightbearing. Femoral head height decreased (mean 1.2 mm, 12.4% decrease), width increased (mean 2.5 mm, 7.2% increase), and lateral extrusion increased (median 2.5 mm, 23% increase) on standing weightbearing MRI compared to supine scans. Negligible deformation was observed in contra-lateral unaffected hips, with less deformation observed in late-stage hips. Inter- and intraclass reliability for all measured parameters was good to excellent. CONCLUSION: This pilot study has described an effective novel research investigation for children with LCPD. Femoral heads in early-stage LCPD demonstrated dynamic deformity on weightbearing not previously seen, while unaffected hips did not. Expansion of this protocol will allow further translational study into the effects of loading hips with LCPD.Cite this article: Bone Joint Open 2020;1-7:364-369.

Repeated Pelvic Radiographs in Infants, After Harness Treatment for Developmental Dysplasia of the Hip, Carry Very Low Radiation Risk.

OBJECTIVE: There are no data on the effect of X-Ray irradiation to the vulnerable pelvic organs of babies during DDH follow-up. This study aims to calculate, for the first time, the radiation exposure to infants during follow-up for DDH harness treatment, and thus quantify the lifetime risk of malignancy. METHODS: Patients who had completed 5 years' follow-up following successful Pavlik harness treatment were identified from the hospital DDH database. The radiation dose was extracted from the Computerised Radiology Information System database for every radiograph of every patient. The effective dose (ED) was calculated using conversion coefficients for age, sex and body region irradiated. Cumulative ED was compared to Health Protection Agency standards to calculate lifetime risk of malignancy from the radiographs. RESULTS: All radiographs of 40 infants, successfully treated in Pavlik harness for DDH, were assessed. The mean number of AP pelvis radiographs was 7.00 (range: 6-9, mode: 7). The mean cumulative ED was 0.25 mSv (Range: 0.11-0.46, SD: 0.07). This is far lower than the annual 'safe' limit for healthcare workers of 20 mSv and is categorised as "Very Low Risk". CONCLUSION: Clinicians involved in the treatment DDH can be re-assured that the cumulative radiation exposure from pelvic radiographs following Pavlik harness treatment is "Very Low Risk". Whilst being mindful of any radiation exposure in children, this study provides a scientific answer that help addresses parental concerns.

Evolution of Legg-Calvé-Perthes disease following proximal femoral varus osteotomy performed in the avascular necrosis stage:a prospective study.

PURPOSE: This prospective study was undertaken to describe patterns of fragmentation of the femoral epiphysis following a proximal femoral varus osteotomy (PFVO) done during stage I of LCPD and to assess the disease duration and outcome in each pattern. METHODS: A total of 25 children treated by a PFVO in stage I of LCPD were followed until healing. The MRI Perfusion Index, radiographic changes in the femoral epiphysis, disease duration and the Sphericity Deviation Score (SDS) at healing were documented. The reproducibility of classification of the pattern of fragmentation, estimation of disease duration and SDS were assessed. The duration of the disease and SDS in the patterns of fragmentation were compared. RESULTS: Four patterns of fragmentation were noted, namely, typical fragmentation, bypassing fragmentation, abortive fragmentation and atypical fragmentation with horizontal fissuring. The reproducibility of classifying the pattern of fragmentation was moderate (Kappa: 0.48) while the reproducibility of other continuous variables was excellent. The Perfusion Index was less than 50% in every affected hip. The duration of the disease and SDS were lowest in children in whom the stage of fragmentation was bypassed but these differences were not statistically significant. CONCLUSION: Following a proximal femoral osteotomy during stage I of LCPD the fragmentation stage may be bypassed partially or completely and the chances of a good outcome appear to be very good if fragmentation is bypassed. LEVEL OF EVIDENCE: Level II Prognostic Study.

Is the modified Gartland classification system important in deciding the need for operative management of supracondylar humerus fractures?

PURPOSE: This study examined levels of agreement between paediatric orthopaedic surgeons in the need for operative management of extension-type supracondylar humerus fractures. METHODS: This was the second phase of a two-part study. De-identified baseline anteroposterior and lateral elbow radiographs from 60 paediatric patients with extension-type supracondylar humerus fractures were compiled. After classifying each fracture according to Gartland classification guidelines, radiographs were randomized, and surgeons indicated whether they would use operative or non-operative management to treat each fracture. Kappa statistics using pairwise comparisons were calculated to determine agreement levels. RESULTS: In total, 11 international surgeons participated, and 10/11 completed both survey rounds. The overall weighted interobserver agreement was moderate (0.530, 95%CI [0.215,0.854]) while overall weighted intraobserver agreement was substantial (0.740, 95%CI [0.513,0.963]). The largest variability in preferred treatment methods between surgeons was observed for type IIA fractures, with 6/11 preferring non-operative and 5/11 preferring operative management. The largest individual surgeon variability was observed for type IIA fractures, with 8/11 showing variability (defined by not having made the same decision for at least 90% of the cases) in choosing whether to operate. CONCLUSIONS: Our findings suggest moderate interobserver, and substantial intraobserver agreement in treatment decision making. The largest disagreements between surgeons were observed for type IIA and IIB fractures and treatment decisions did not follow expected trends based on surgeons' preferred treatment methods for each fracture type. This suggests differences in treatment approaches between surgeons in the management of type IIA fractures and highlights the role of other variables that underlie differences between surgeons' treatment preferences. LEVEL OF EVIDENCE: III.

Paediatric axillary artery pseudo-aneurysm after simple shoulder dislocation.

We report the unique case of a 14-year-old male with axillary artery pseudo-aneurysm associated with brachial plexus compression after a simple shoulder dislocation. Following shoulder reduction under anaesthetic, the child was discharged on chemical deep vein thrombosis (DVT) prophylaxis. However, progressive shoulder swelling and upper limb neurological symptoms developed. A multi-disciplinary approach was taken to diagnose and treat this complication. After stopping the anti-coagulants, a combination of endovascular stent-graft and open surgical decompression of the brachial plexus was employed. Paediatric guidelines on DVT prophylaxis are scarce but DVT has never been reported in children following upper limb trauma.

Triplane Fracture of the Proximal Tibia: A Case Report and Literature Review.

BACKGROUND: The triplane fracture, a unique transitional physeal injury, is classically described in the distal tibia. A small number of additional anatomic locations are documented in the orthopaedic literature. METHODS: Available literature surrounding triplane fractures was reviewed. We describe a rare case of a proximal tibial triplane fracture in a thirteen-year-old girl, suffered during a skiing accident. RESULTS: Using arthroscopically assisted percutaneous reduction techniques an anatomic reduction was achieved. CONCLUSION: We outline the surgical and postoperative techniques for management of this unique injury.

Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies; translational issues.

Binary blend polymers offer the opportunity to combine different desirable properties into a single scaffold, to enhance function within the field of tissue engineering. Previous in vitro and murine in vivo analysis identified a polymer blend of poly(l-lactic acid)-poly(ε-caprolactone) (PLLA:PCL 20:80) to have characteristics desirable for bone regeneration. Polymer scaffolds in combination with marrow-derived skeletal stem cells (SSCs) were implanted into mid-shaft ovine 3.5 cm tibial defects, and indices of bone regeneration were compared to groups implanted with scaffolds alone and with empty defects after 12 weeks, including micro-CT, mechanical testing and histological analysis. The critical nature of the defect was confirmed via all modalities. Both the scaffold and scaffold/SSC groups showed enhanced quantitative bone regeneration; however, this was only found to be significant in the scaffold/SSCs group (p = 0.04) and complete defect bridging was not achieved in any group. The mechanical strength was significantly less than that of contralateral control tibiae (p < 0.01) and would not be appropriate for full functional loading in a clinical setting. This study explored the hypothesis that cell therapy would enhance bone formation in a critical-sized defect compared to scaffold alone, using an external fixation construct, to bridge the scale-up gap between small animal studies and potential clinical translation. The model has proved a successful critical defect and analytical techniques have been found to be both valid and reproducible. Further work is required with both scaffold production techniques and cellular protocols in order to successfully scale-up this stem cell/binary blend polymer scaffold. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

The effect of porosity of a biphasic ceramic scaffold on human skeletal stem cell growth and differentiation in vivo.

Skeletal stem cell (SSC) growth on a novel porous HA/TCP scaffold has been investigated in vivo. The effect of porosity on osteogenic differentiation was assessed by comparing two groups of scaffolds with differing porosity but controlled pore size. Histology, microCT, scanning electron microscopy, and biochemical analysis were used to assess SSC proliferation and differentiation. The 45 pores per inch (ppi) scaffold demonstrated a greater increase in density than the 30 ppi scaffold following in vivo culture, and a reduction in dimensions of the pores and channels of the higher porosity scaffold was observed, indicating generation of new tissue within the pores. All scaffolds supported SSC proliferation but the higher scaffold porosity augmented osteogenic differentiation. ALP specific activity was enhanced on the 45 ppi scaffold compared to the 30 ppi scaffold. These studies demonstrate the importance of porosity in scaffold design and impact therein for tissue engineering application.

Effects of setting bone cement on tissue-engineered bone graft: a potential barrier to clinical translation?

BACKGROUND: Strategies to improve mechanical strength, neovascularization, and the regenerative capacity of allograft include both the addition of skeletal stem cells and the investigation of novel biomaterials to reduce and ultimately obviate the need for allograft altogether. Use of bone cement is a common method of stabilizing implants in conjunction with impacted allograft. Curing cement, however, can reach temperatures in excess of 70°C, which is potentially harmful to skeletal stem cells. The aim of this study was to investigate the effects of setting bone cement on the survival of human adult skeletal stem cells within tissue-engineered allograft and a novel allograft substitute. METHODS: Milled allograft and a polymer graft substitute were seeded with skeletal stem cells, impacted into a graduated chamber, and exposed to curing bone cement. Sections were removed at 5-mm increments from the allograft-cement interface. A quantitative WST-1 assay was performed on each section as a measure of remaining cell viability. A second stage of the experiment involved assessment of methods to potentially enhance cell survival, including pretreating the allograft or polymer by either cooling to 5°C or coating with 1% Laponite, or both. RESULTS: There was a significant drop in cellular activity in the sections taken from within 0.5 cm of the cement interface in both the allograft and the polymer (p < 0.05), although there was still measurable cellular activity. Pretreatment methods did not significantly improve cell survival in any group. CONCLUSIONS: While the addition of bone cement reduced cellular viability of tissue-engineered constructs, this reduction occurred only in close proximity to the cement and measurable numbers of skeletal stem cells were observed, confirming the potential for cell population recovery.

The role of osteoblast cells in the pathogenesis of unicameral bone cysts.

PURPOSE: The pathogenesis of unicameral bone cysts (UBCs) remains largely unknown. Osteoclasts have been implicated, but the role of osteoblastic cells has, to date, not been explored. This study investigated the pathophysiology of UBCs by examining the interactions between the cyst fluid and human bone marrow stromal cells (hBMSCs) and the effect of the fluid on osteogenesis. METHODS: Fluid was aspirated from two UBCs and analysed for protein, electrolyte and cytokine levels. Graded concentrations of the fluid were used as culture media for hBMSCs to determine the effects of the fluid on hBMSC proliferation and osteogenic differentiation. The fibrocellular lining was analysed histologically and by electron microscopy. RESULTS: Alkaline phosphatase (ALP) staining of hBMSCs that were cultured in cyst fluid demonstrated increased cell proliferation and osteogenic differentiation compared to basal media controls. Biochemical analysis of these hBMSCs compared to basal controls confirmed a marked increase in DNA content (as a marker of proliferation) and ALP activity (as a marker of osteogenic differentiation) which was highly significant (p < 0.001). Osteoclasts were demonstrated in abundance in the cyst lining. The cyst fluid cytokine profile revealed levels of the pro-osteoclast cytokines IL-6, MIP-1α and MCP-1 that were 19×, 31× and 35× greater than those in reference serum. CONCLUSIONS: Cyst fluid promoted osteoblastic growth and differentiation. Despite appearing paradoxical that the cyst fluid promoted osteogenesis, osteoblastic cells are required for osteoclastogenesis through RANKL signalling. Three key cytokines in this pathway (IL-6, MIP-1α, MCP-1) were highly elevated in cyst fluid. These findings may hold the key to the pathogenesis of UBCs, with implications for treatment methods.

An analysis of polymer type and chain length for use as a biological composite graft extender in impaction bone grafting: a mechanical and biocompatibility study.

Impaction bone grafting (IBG) with human allograft remains the preferred approach for replacement of lost bone stock during revision hip surgery. Associated problems include cost, disease transmission, and stem subsidence. Synthetic grafts are therefore appealing, and ideally display similar mechanical characteristics as allograft, but with enhanced ability to form de novo bone. High and low molecular weight forms of three different polymers [poly(DL-lactide) (P(DL) LA), poly(DL-lactide-co-glycolide) (P(DL) LGA), and poly(ε-caprolactone) (PCL)] were milled, impacted into discs, and then examined in a shear testing rig, in comparison to allograft. In addition, skeletal stem cells (SSCs) were combined with each of the milled polymers, followed by impaction and examination for cell viability and number, via fluorostaining and biochemical assays. The shear strengths of high/low mwt P(DL) LA, and high/low mwt P(DL) LGA were significantly higher than allograft (p < 0.01). High/low mwt PCL had significantly lower shear strengths (p < 0.01). WST-1 assay and fluorstaining indicated significantly increased cell viability on high mwt P(DL) LA and high mwt P(DL) LGA over allograft (p < 0.05). Mechanical and biochemical analysis indicated improved properties of high mwt P(DL) LA and high mwt P(DL) LGA over allograft. This study indicates the potential of these polymers for use as substitute human allograft, creating a living composition with SSC for application in IBG.

Skeletal tissue regeneration: current approaches, challenges, and novel reconstructive strategies for an aging population.

Loss of skeletal tissue as a consequence of trauma, injury, or disease is a significant cause of morbidity with often wide-ranging socioeconomic impacts. Current approaches to replace or restore significant quantities of lost bone come with substantial limitations and inherent disadvantages that may in themselves cause further disability. In addition, the spontaneous repair capacity of articular cartilage is limited; thus, investigation into new cartilage replacement and regeneration techniques are warranted. Along with the challenges of an increasingly aging demographic, changing clinical scenarios and rising functional expectations provide the imperative for new, more reliable skeletal regeneration strategies. The science of tissue engineering has expanded dramatically in recent years, notably in orthopedic applications, and it is clear that new approaches for de novo skeletal tissue formation offer exciting opportunities to improve the quality of life for many, particularly in the face of increasing patient expectations. However, significant scientific, financial, industrial, and regulatory challenges should be overcome before the successful development of an emergent tissue engineering strategy can be realized. We outline current practice for replacement of lost skeletal tissue and the innovative approaches in tissue regeneration that have so far been translated to clinical use, along with a discussion of the significant hurdles that are presented in the process of translating research strategies to the clinic.