Hydrodynamic control of titania nanotube formation on Ti-6Al-4V alloys enhances osteogenic differentiation of human mesenchymal stromal cells.

In order to obtain bioactive bone-implant interfaces with enhanced osteogenic capacity, various approaches have been developed to modify surface physicochemical properties of bio-inert titanium and titanium alloys. One promising strategy involves fabricating highly ordered nanotubes (NT) on implant surfaces via electrochemical anodization. However, few studies have applied this technique to Ti-6Al-4V alloys most commonly adopted for the fabrication of osteo-integrated surfaces on orthopedic implants. In this study, we investigated the influence of electrolyte hydrodynamics to NT fabrication on Ti-6Al-4V in ethylene glycol based electrolyte and evaluated the osteogenic differentiation capacity of human mesenchymal stromal cells (hMSCs) on different diameter NT surfaces. Computational Fluid Dynamics (CFD) analysis was used to simulate electrolyte flow profiles under various stirring conditions (e.g. stirrer bar location and flow direction) and their correlation to NT formation. Polished Ti-6Al-4V disks (240 grit) were anodized at 20 and 40 V under optimal electrolyte flow conditions for comparison of NT diameter-controlled osteogenic differentiation and mineralization potential of hMSCs over 21 days culture in osteogenic media. Ti-6Al-4V surfaces anodized with 20 and 40 V resulted with NTs diameter approx. 39 and 83 nm, respectively. Electrolyte hydrodynamics (flow profile) significantly influenced the uniformity of NT formation. Here, a uniform velocity and shear stress profile at the surface promoted homogeneous NT growth, whereas large variation in either flow velocity or shear stress to the surface impaired mature NT formation. After 21 days of culture, fluorescence staining demonstrated significantly greater osteocalcin and osteopontin expression, and increased mineralized deposits (xylenol orange staining) on fluctuating NT surfaces anodized under 20 V (Ø 39 nm) relative to flat NT layer anodized with 40 V (Ø 83 nm) and polished controls. This study provides a systematic investigation of NT formation with respect to the electrolyte hydrodynamic effects to NT growth on Ti-6Al-4V alloys, demonstrating the feasibility of a one-step anodization process for generating uniform NT under optimal hydrodynamics. Optimized wavy micro-/nano-topography with Ø 39 nm NT stimulated osteogenic differentiation capacity of hMSCs on Ti-6Al-4V alloys and confirmed the potential application of anodization to improve osteo-integrative surfaces in orthopedic implants.

Intact vitreous humor as a potential extracellular matrix hydrogel for cartilage tissue engineering applications.

Decellularisation of tissues, utilising their biochemical cues, poses exciting tissue engineering (TE) opportunities. However, removing DNA from cartilage (dCart) requires harsh treatments due to its dense structure, causing loss of bioactivity and limiting its application as a cartilaginous extra cellular matrix (ECM). In this study, we demonstrate for the first time the successful application of vitreous humor (VH), a highly hydrated tissue closely resembling the glycosaminoglycan (GAG) and collagen composition of cartilage, as an ECM hydrogel to support chondrogenic differentiation. Equine VH was extracted followed by biochemical quantifications, histological examinations, cytotoxicity (human mesenchymal stromal cells, hMSCs and human articular chondrocytes, hACs) and U937 cell proliferation studies. VH was further seeded with hACs or hMSCs and cultured for 3-weeks to study chondrogenesis compared to scaffold-free micro-tissue pellet cultures and collagen-I hydrogels. Viability, metabolic activity, GAG and DNA content, chondrogenic gene expression (aggrecan, collagen I/II mRNA) and mechanical properties were quantified and matrix deposition was visualised using immunohistochemistry (Safranin-O, collagen I/II). VH was successfully extracted, exhibiting negligible amounts of DNA (0.4 ±â€¯0.4 µg/mg dry-weight) and notable preservation of ECM components. VH displayed neither cytotoxic responses nor proliferation of macrophage-like U937 cells, instead enhancing both hMSC and hAC proliferation. Interestingly, encapsulated cells self-assembled the VH-hydrogel into spheroids, resulting in uniform distribution of both GAGs and collagen type II with increased compressive mechanical properties, rendering VH a permissive native ECM source to fabricate cartilaginous hydrogels for potential TE applications. STATEMENT OF SIGNIFICANCE: Fabricating bioactive and cell-instructive cartilage extracellular matrix (ECM) derived biomaterials and hydrogels has over recent years proven to be a challenging task, often limited by poor retention of inherent environmental cues post decellularisation due to the dense and avascular nature of native cartilage. In this study, we present an alternative route to fabricate highly permissive and bioactive ECM hydrogels from vitreous humor (VH) tissue. This paper specifically reports the discovery of optimal VH extraction protocols and cell seeding strategy enabling fabrication of cartilaginous matrix components into a hydrogel support material for promoting chondrogenic differentiation. The work showcases a naturally intact and unmodified hydrogel design that improves cellular responses and may help guide the development of cell instructive and stimuli responsive hybrid biomaterials in a number of TERM applications.

A 96-well microplate bioreactor platform supporting individual dual perfusion and high-throughput assessment of simple or biofabricated 3D tissue models.

Traditional 2D monolayer cell cultures and submillimeter 3D tissue construct cultures used widely in tissue engineering are limited in their ability to extrapolate experimental data to predict in vivo responses due to their simplistic organization and lack of stimuli. The rise of biofabrication and bioreactor technologies has sought to address this through the development of techniques to spatially organize components of a tissue construct, and devices to supply these tissue constructs with an increasingly in vivo-like environment. Current bioreactors supporting both parenchymal and barrier tissue constructs in interconnected systems for body-on-a-chip platforms have chosen to emphasize study throughput or system/tissue complexity. Here, we report a platform to address this disparity in throughput and both system complexity (by supporting multiple in situ assessment methods) and tissue complexity (by adopting a construct-agnostic format). We introduce an ANSI/SLAS-compliant microplate and docking station fabricated via stereolithography (SLA), or precision machining, to provide up to 96 samples (Ø6 × 10 mm) with two individually-addressable fluid circuits (192 total), loading access, and inspection window for imaging during perfusion. Biofabricated ovarian cancer models were developed to demonstrate the in situ assessment capabilities via microscopy and a perfused resazurin-based metabolic activity assay. In situ microscopy highlighted flexibility of the sample housing to accommodate a range of sample geometries. Utility for drug screening was demonstrated by exposing the ovarian cancer models to an anticancer drug (doxorubicin) and generating the dose-response curve in situ, while achieving an assay quality similar to static wellplate culture. The potential for quantitative analysis of temporal tissue development and screening studies was confirmed by imaging soft- (gelatin) and hard-tissue (calcium chloride) analogs inside the bioreactor via spectral computed tomography (CT) scanning. As a proof-of-concept for particle tracing studies, flowing microparticles were visualized to inform the design of hydrogel constructs. Finally, the ability for mechanistic yet high-throughput screening was demonstrated in a vascular coculture model adopting endothelial and mesenchymal stem cells (HUVEC-MSC), encapsulated in gelatin-norbornene (gel-NOR) hydrogel cast into SLA-printed well inserts. This study illustrates the potential of a scalable dual perfusion bioreactor platform for parenchymal and barrier tissue constructs to support a broad range of multi-organ-on-a-chip applications.

The impact of patient and surgical factors on the rate of infection after primary total knee arthroplasty: an analysis of 64,566 joints from the New Zealand Joint Registry.

AIMS: The aim of this study was to identify risk factors for prosthetic joint infection (PJI) following total knee arthroplasty (TKA). PATIENTS AND METHODS: The New Zealand Joint Registry database was analysed, using revision surgery for PJI at six and 12 months after surgery as primary outcome measures. Statistical associations between revision for infection, with common and definable surgical and patient factors were tested. RESULTS: A total of 64 566 primary TKAs have been recorded on the registry between 1999 and 2012 with minimum follow-up of 12 months. Multivariate analysis showed statistically significant associations with revision for PJI between male gender (odds ratio (OR) 1.85, 95% confidence interval (CI) 1.24 to 2.74), previous surgery (osteotomy (OR 2.45 95% CI 1.2 to 5.03), ligament reconstruction (OR 1.85, 95% CI 0.68 to 5.00)), the use of laminar flow (OR 1.6, 95% CI 1.04 to 2.47) and the use of antibiotic-laden cement (OR 1.93, 95% CI 1.19 to 3.13). There was a trend towards significance (p = 0.052) with the use of surgical helmet systems at six months (OR 1.53, 95% CI 1.00 to 2.34). CONCLUSION: These findings show that patient factors remain the most important in terms of predicting early PJI following TKA. Furthermore, we found no evidence that modern surgical helmet systems reduce the risk of PJI and laminar flow systems may actually increase risk in TKA. The use of this registry data assists the estimation of the risk of PJI for individual patients, which is important for both informed consent and the interpretation of infection rates at different institutions. TAKE HOME MESSAGE: Infection rates in TKA are related to both individual patient and surgical factors, and some modern methods of reducing infection may actually increase infection risk.

Cementless fixation in Oxford unicompartmental knee replacement: a multicentre study of 1000 knees.

The Cementless Oxford Unicompartmental Knee Replacement (OUKR) was developed to address problems related to cementation, and has been demonstrated in a randomised study to have similar clinical outcomes with fewer radiolucencies than observed with the cemented device. However, before its widespread use it is necessary to clarify contraindications and assess the complications. This requires a larger study than any previously published. We present a prospective multicentre series of 1000 cementless OUKRs in 881 patients at a minimum follow-up of one year. All patients had radiological assessment aligned to the bone-implant interfaces and clinical scores. Analysis was performed at a mean of 38.2 months (19 to 88) following surgery. A total of 17 patients died (comprising 19 knees (1.9%)), none as a result of surgery; there were no tibial or femoral loosenings. A total of 19 knees (1.9%) had significant implant-related complications or required revision. Implant survival at six years was 97.2%, and there was a partial radiolucency at the bone-implant interface in 72 knees (8.9%), with no complete radiolucencies. There was no significant increase in complication rate compared with cemented fixation (p = 0.87), and no specific contraindications to cementless fixation were identified. Cementless OUKR appears to be safe and reproducible in patients with end-stage anteromedial osteoarthritis of the knee, with radiological evidence of improved fixation compared with previous reports using cemented fixation.

The early radiological results of the uncemented Oxford medial compartment knee replacement.

We carried out a prospective investigation into the radiological outcomes of uncemented Oxford medial compartment unicondylar replacement in 220 consecutive patients (231 knees) performed in a single centre with a minimum two-year follow-up. The functional outcomes using the mean Oxford knee score and the mean high-activity arthroplasty score were significantly improved over the pre-operative scores (p < 0.001). There were 196 patients with a two-year radiological examination performed under fluoroscopic guidance, aiming to provide images acceptable for analysis of the bone-implant interface. Of the six tibial zones examined on each knee on the anteroposterior radiograph, only three had a partial radiolucent line. All were in the medial aspect of the tibial base plate (zone 1) and all measured < 1 mm. All of these patients were asymptomatic. There were no radiolucent lines seen around the femoral component or on the lateral view. There was one revision for loosening at one year due to initial inadequate seating of the tibial component. These results confirm that the early uncemented Oxford medial unicompartmental compartmental knee replacements were reliable and the incidence of radiolucent lines was significantly decreased compared with the reported results of cemented versions of this implant. These independent results confirm those of the designing centre.

Does the use of laminar flow and space suits reduce early deep infection after total hip and knee replacement?: the ten-year results of the New Zealand Joint Registry.

We have investigated whether the use of laminar-flow theatres and space suits reduced the rate of revision for early deep infection after total hip (THR) and knee (TKR) replacement by reviewing the results of the New Zealand Joint Registry at ten years. Of the 51 485 primary THRs and 36 826 primary TKRs analysed, laminar-flow theatres were used in 35.5% and space suits in 23.5%. For THR there was a significant increase in early infection in those procedures performed with the use of a space suit compared with those without (p < 0.0001), in those carried out in a laminar-flow theatre compared with a conventional theatre (p < 0.003) and in those undertaken in a laminar-flow theatre with a space suit (p < 0.001) when compared with conventional theatres without such a suit. The results were similar for TKR with the use of a space suit (p < 0.001), in laminar-flow theatres (p < 0.019) and when space suits were used in those theatres (p < 0.001). These findings were independent of age, disease and operating time and were unchanged when the surgeons and hospital were analysed individually. The rate of revision for early deep infection has not been reduced by using laminar flow and space suits. Our results question the rationale for their increasing use in routine joint replacement, where the added cost to the health system seems to be unjustified.

Survival and functional outcome after revision of a unicompartmental to a total knee replacement: the New Zealand National Joint Registry.

We reviewed the rate of revision of unicompartmental knee replacements (UKR) from the New Zealand Joint Registry between 1999 and 2008. There were 4284 UKRs, of which 236 required revision, 205 to a total knee replacement (U2T) and 31 to a further unicompartmental knee replacement (U2U). We used these data to establish whether the survival and functional outcome for revised UKRs were comparable with those of primary total knee replacement (TKR). The rate of revision for the U2T cohort was four times higher than that for a primary TKR (1.97 vs 0.48; p < 0.05). The mean Oxford Knee Score was also significantly worse in the U2T group than that of the primary TKR group (30.02 vs 37.16; p < 0.01). The rate of revision for conversion of a failed UKR to a further UKR (U2U cohort) was 13 times higher than that for a primary TKR. The poor outcome of a UKR converted to a primary TKR compared with a primary TKR should contra-indicate the use of a UKR as a more conservative procedure in the younger patient.

An analysis of the Oxford hip and knee scores and their relationship to early joint revision in the New Zealand Joint Registry.

We analysed data from the Oxford hip and knee questionnaires collected by the New Zealand Joint Registry at six months and five years after joint replacement, to determine if there was any relationship between the scores and the risk of early revision. Logistic regression of the six-month scores indicated that for every one-unit decrease in the Oxford score, the risk of revision within two years increased by 9.7% for total hip replacement (THR), 9.9% for total knee replacement (TKR) and 12.0% for unicompartmental knee replacement (UKR). Our findings showed that 70% of the revisions within two years for TKR and 67% for THR and UKR would have been captured by monitoring the lowest 22%, 28% and 28%, respectively, of the Oxford scores. When analysed using the Kalairajah classification a score of < 27 (poor) was associated with a risk of revision within two years of 7.6% for THR, 7.0% for TKR and 24.3% for UKR, compared with risks of 0.7%, 0.7% and 1.8%, respectively, for scores > 34 (good or excellent). Our study confirms that the Oxford hip and knee scores at six months are useful predictors of early revision after THR and TKR and we recommend their use for the monitoring of the outcome and potential failure in these patients.

Revision following cemented and uncemented primary total hip replacement: a seven-year analysis from the New Zealand Joint Registry.

We have reviewed the rate of revision of fully cemented, hybrid and uncemented primary total hip replacements (THRs) registered in the New Zealand Joint Registry between 1999 and December 2006 to determine whether there was any statistically significant difference in the early survival and reason for revision in these different types of fixation. The percentage rate of revision was calculated per 100 component years and compared with the reason for revision, the type of fixation and the age of the patients. Of the 42 665 primary THRs registered, 920 (2.16%) underwent revision requiring change of at least one component. Fully-cemented THRs had a lower rate of revision when considering all causes for failure (p < 0.001), but below the age of 65 years uncemented THRs had a lower rate (p < 0.01). The rate of revision of the acetabular component for aseptic loosening was less in the uncemented and hybrid groups compared with that in the fully cemented group (p < 0.001), and the rate of revision of cemented and uncemented femoral components was similar, except in patients over 75 years of age in whom revision of cemented femoral components was significantly less frequent (p < 0.02). Revision for infection was more common in patients aged below 65 years and in cemented and hybrid THRs compared with cementless THRs (p < 0.001). Dislocation was the most common cause of revision for all types of fixation and was more frequent in both uncemented acetabular groups (p < 0.001). The experience of the surgeon did not affect the findings. Although cemented THR had the lowest rate of revision for all causes in the short term (90 days), uncemented THR had the lowest rate of aseptic loosening in patients under 65 years of age and had rates comparable with international rates of aseptic loosening in those over 65 years.

Screening for breast cancer: time, travel, and out-of-pocket expenses.

BACKGROUND: We estimated the personal costs to women found to have a breast problem (either breast cancer or benign breast disease) in terms of time spent, miles traveled, and cash payments made for detection, diagnosis, initial treatment, and follow-up. METHODS: We analyzed data from personal interviews with 465 women from four communities in Florida. These women were randomly selected from those with a recent breast biopsy (within 6-8 months) that indicated either breast cancer (208 women) or benign breast disease (257 women). One community was the site of a multifaceted intervention to promote breast screening, and the other three communities were comparison sites for evaluation of that intervention. All P values are two-sided. RESULTS: In comparison with time spent and travel distance for women with benign breast disease (13 hours away from home and 56 miles traveled), time spent and travel distance were statistically significantly higher (P<.001) for treatment and follow-up of women with breast cancer (89 hours and 369 miles). Personal financial costs for treatment of women with breast cancer were also statistically significantly higher (breast cancer = $604; benign breast disease = $76; P < .001) but were statistically significantly lower for detection and diagnosis (breast cancer = $170; benign breast disease = $310; P < .001). Among women with breast cancer, time spent for treatment was statistically significantly lower (P = .013) when their breast cancer was detected by screening (68.9 hours) than when it was detected because of symptoms (84.2 hours). Personal cash payments for detection, diagnosis, and treatment were statistically significantly lower among women whose breast problems were detected by screening than among women whose breast problems were detected because of symptoms (screening detected = $453; symptom detected = $749; P = .045). CONCLUSION: There are substantial personal costs for women who are found to have a breast problem, whether the costs are associated with problems identified through screening or because of symptoms.

Conservative management or closed nailing for tibial shaft fractures. A randomised prospective trial.

We performed a prospective randomised trial on matched groups of patients with displaced tibial shaft fractures to compare conservative treatment with closed intramedullary nailing. The results showed conclusively that intramedullary nailing gave more rapid union with less malunion and shortening. Nailed patients had less time off work with a more predictable and rapid return to full function. We therefore consider that closed intramedullary nailing is the most efficient treatment for displaced fractures of the tibial shaft.

Closed unlocked nailing for comminuted femoral fractures.

Fifty consecutive comminuted fractures of the femoral shaft were treated by closed unlocked intramedullary nailing. Twelve unstable fractures also had cast-bracing. There were no cases of infection or non-union, and satisfactory results were achieved in 38 fractures (76%). More severe comminution led to a higher incidence of unsatisfactory results, but malrotation deformity was seen more often in less comminuted fractures and appeared to be due to poor operative reduction. Shortening in severe comminution was the main complication and was not controlled by supplementary cast-bracing. Closed unlocked intramedullary nailing is effective for lesser grades of comminution, but fractures with no cortical continuity at reduction should be treated with a locking nail.

Reconstruction of the anterior cruciate ligament using the bone-block iliotibial-tract transfer.

The results of reconstructing the torn anterior cruciate ligament using the bone-block iliotibial-tract transfer in thirty-seven patients were reviewed. After the operation, only one patient considered the function of the knee to be normal, but most (all but four) could participate in moderately strenuous work activities and some sports activities. The athletes who were operated on rarely were able to return to their pre-injury level of activity. Most of the patients continued to have clinical evidence of deficiency of the anterior cruciate ligament. All but five had a positive Lachman test and most had a positive pivot-shift sign. Fifteen results were rated satisfactory and ten were rated poor. Because of these disappointing results we have discontinued using the procedure.

An unusual variety of skier's thumb.

An unusual thumb injury with an avulsion of the ulnar collateral ligament of the metacarpophalangeal joint and simultaneous dislocation of the carpometacarpal joint is presented. Immediate repair of the ruptured structures at both joints produced a satisfactory result.

Radiological assessment of anterior cruciate ligament deficiency. A new technique.

A new method of demonstrating sagittal laxity in the anterior cruciate-deficient knee is described. Seventy such knees were compared to 70 normal knees. Sagittal laxity was recorded as the average displacement of the medial and lateral femoral condyles. This displacement index was significantly different between the two groups of knees (P less than 0.0001). A range for normal and abnormal knees is discussed. Quantitative assessment of the degree of sagittal laxity by clinical evaluation is shown to be unreliable. Only the pivot-shift test demonstrated any significant correlation with the amount of sagittal displacement (P less than 0.05).