Material-driven fibronectin and vitronectin assembly enhances BMP-2 presentation and osteogenesis.

Mesenchymal stem cell (MSC)-based tissue engineering strategies are of interest in the field of bone tissue regenerative medicine. MSCs are commonly investigated in combination with growth factors (GFs) and biomaterials to provide a regenerative environment for the cells. However, optimizing how biomaterials interact with MSCs and efficiently deliver GFs, remains a challenge. Here, via plasma polymerization, tissue culture plates are coated with a layer of poly (ethyl acrylate) (PEA), which is able to spontaneously permit fibronectin (FN) to form fibrillar nanonetworks. However, vitronectin (VN), another important extracellular matrix (ECM) protein forms multimeric globules on the polymer, thus not displaying functional groups to cells. Interestingly, when FN and VN are co-absorbed onto PEA surfaces, VN can be entrapped within the FN fibrillar nanonetwork in the monomeric form providing a heterogeneous, open ECM network. The combination of FN and VN promote MSC adhesion and leads to enhanced GF binding; here we demonstrate this with bone morphogenetic protein-2 (BMP2). Moreover, MSC differentiation into osteoblasts is enhanced, with elevated expression of osteopontin (OPN) and osteocalcin (OCN) quantified by immunostaining, and increased mineralization observed by von Kossa staining. Osteogenic intracellular signalling is also induced, with increased activity in the SMAD pathway. The study emphasizes the need of recapitulating the complexity of native ECM to achieve optimal cell-material interactions.

Extended Tourniquet Times and the Impact on Wound Healing in Foot Surgery.

OBJECTIVE: The aim of this study was to compare the effect of tourniquet time less than or in excess of 120 minutes on foot surgery wound healing. NULL HYPOTHESIS: A tourniquet time of over 120 minutes will not affect wound healing in foot surgery. DESIGN, SETTING, PARTICIPANTS AND METHOD: A retrospective comparative cohort analysis was performed on 96 patients undergoing complex hindfoot surgery in a large central teaching hospital. Fifty-five patients receiving tourniquet pressure for >120 minutes and 41 receiving <120 minutes of tourniquet pressure were identified from electronic case records. The primary outcome was surgical wound healing. Secondary outcomes were discharge date and complication rate. RESULTS: There was no significant difference in reported time for wounds to heal in the <120-minute or >120-minute cohort. There were no other significant differences in secondary clinical outcomes and no significant variations in patient demographics. CONCLUSION: This study suggests that tourniquet times from 2 to 3 hours in foot and ankle surgery with pressures up to 300 mmHg are not associated with a significant effect on wound healing.

Cement-in-cement versus uncemented modular stem revision for Vancouver B2 periprosthetic fractures.

Background: To compare outcomes of revision to a long uncemented stem with cement-in-cement revision for Vancouver B2 periprosthetic fracture (PPF). Methods: Patients undergoing surgery for a Vancouver B2 PPF in a cemented stem from 2008 to 2018 were identified using our prospectively collated database. Results: We identified 43 uncemented and 29 cement-in-cement revisions. Cement-in-cement revision had a shorter operative time, reduction in certain complications, no increased rate of non-union, lower degree of stem subsidence and no difference in re-revision rate. Conclusion: With appropriate patient selection, both cement-in-cement and long uncemented stem revision represent appropriate treatment options for Vancouver B2 fractures.

Materials-driven fibronectin assembly on nanoscale topography enhances mesenchymal stem cell adhesion, protecting cells from bacterial virulence factors and preventing biofilm formation.

Post-operative infection is a major complication in patients recovering from orthopaedic surgery. As such, there is a clinical need to develop biomaterials for use in regenerative surgery that can promote mesenchymal stem cell (MSC) osteospecific differentiation and that can prevent infection caused by biofilm-forming pathogens. Nanotopographical approaches to pathogen control are being identified, including in orthopaedic materials such as titanium and its alloys. These topographies use high aspect ratio nanospikes or nanowires to prevent bacterial adhesion but these features also significantly reduce MSC adhesion and activity. Here, we use a poly (ethyl acrylate) (PEA) polymer coating on titanium nanowires to spontaneously organise fibronectin (FN) and to deliver bone morphogenetic protein 2 (BMP2) to enhance MSC adhesion and osteospecific signalling. Using a novel MSC-Pseudomonas aeruginosa co-culture, we show that the coated nanotopographies protect MSCs from cytotoxic quorum sensing and signalling molecules, enhance MSC adhesion and osteoblast differentiation and reduce biofilm formation. We conclude that the PEA polymer-coated nanotopography can both support MSCs and prevent pathogens from adhering to a biomaterial surface, thus protecting from biofilm formation and bacterial infection, and supporting osteogenic repair.

Interpretation and reporting of predictive or diagnostic machine-learning research in Trauma & Orthopaedics.

There is increasing popularity in the use of artificial intelligence and machine-learning techniques to provide diagnostic and prognostic models for various aspects of Trauma & Orthopaedic surgery. However, correct interpretation of these models is difficult for those without specific knowledge of computing or health data science methodology. Lack of current reporting standards leads to the potential for significant heterogeneity in the design and quality of published studies. We provide an overview of machine-learning techniques for the lay individual, including key terminology and best practice reporting guidelines. Cite this article: Bone Joint J 2021;103-B(12):1754-1758.

Cement-in-cement femoral component revision : a comparison of two different taper-slip designs with medium-term follow up.

AIMS: Cement-in-cement revision of the femoral component represents a widely practised technique for a variety of indications in revision total hip arthroplasty. In this study, we compare the clinical and radiological outcomes of two polished tapered femoral components. METHODS: From our prospectively collated database, we identified all patients undergoing cement-in-cement revision from January 2005 to January 2013 who had a minimum of two years' follow-up. All cases were performed by the senior author using either an Exeter short revision stem or the C-Stem AMT high offset No. 1 prosthesis. Patients were followed-up annually with clinical and radiological assessment. RESULTS: A total of 97 patients matched the inclusion criteria (50 Exeter and 47 C-Stem AMT components). There were no significant differences between the patient demographic data in either group. Mean follow-up was 9.7 years. A significant improvement in Oxford Hip Score (OHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 12-item Short-Form Survey (SF-12) scores was observed in both cohorts. Leg lengths were significantly shorter in the Exeter group, with a mean of -4 mm in this cohort compared with 0 mm in the C-Stem AMT group. One patient in the Exeter group had early evidence of radiological loosening. In total, 16 patients (15%) underwent further revision of the femoral component (seven in the C-Stem AMT group and nine in the Exeter group). No femoral components were revised for aseptic loosening. There were two cases of femoral component fracture in the Exeter group. CONCLUSION: Our series shows promising mid-term outcomes for the cement-in-cement revision technique using either the Exeter or C-Stem AMT components. These results demonstrate that cement-in-cement revision using a double or triple taper-slip design is a safe and reliable technique when used for the correct indications. Cite this article: Bone Joint J 2021;103-B(7):1215-1221.

Cobalt-induced cardiomyopathy - do circulating cobalt levels matter?

Elevated levels of circulating cobalt ions have been linked with a wide range of systemic complications including neurological, endocrine, and cardiovascular symptoms. Case reports of patients with elevated blood cobalt ions have described significant cardiovascular complications including cardiomyopathy. However, correlation between the actual level of circulating cobalt and extent of cardiovascular injury has not previously been performed. This review examines evidence from the literature for a link between elevated blood cobalt levels secondary to metal-on-metal (MoM) hip arthroplasties and cardiomyopathy. Correlation between low, moderate, and high blood cobalt with cardiovascular complications has been considered. Elevated blood cobalt at levels over 250 µg/l have been shown to be a risk factor for developing systemic complications and published case reports document cardiomyopathy, cardiac transplantation, and death in patients with severely elevated blood cobalt ions. However, it is not clear that there is a hard cut-off value and cardiac dysfunction may occur at lower levels. Clinical and laboratory research has found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Further work needs to be done to clarify the link between severely elevated blood cobalt ions and cardiomyopathy. Cite this article: Bone Joint Res 2021;10(6):340-347.

Anatomical pelvic loading of a monoblock polyethylene acetabular component.

AIMS: Uncemented metal acetabular components show good osseointegration, but material stiffness causes stress shielding and retroacetabular bone loss. Cemented monoblock polyethylene components load more physiologically; however, the cement bone interface can suffer fibrous encapsulation and loosening. It was hypothesized that an uncemented titanium-sintered monoblock polyethylene component may offer the optimum combination of osseointegration and anatomical loading. METHODS: A total of 38 patients were prospectively enrolled and received an uncemented monoblock polyethylene acetabular (pressfit) component. This single cohort was then retrospectively compared with previously reported randomized cohorts of cemented monoblock (cemented) and trabecular metal (trabecular) acetabular implants. The primary outcome measure was periprosthetic bone density using dual-energy x-ray absorptiometry over two years. Secondary outcomes included radiological and clinical analysis. RESULTS: Although there were differences in the number of males and females in each group, no significant sex bias was noted (p = 0.080). Furthermore, there was no significant difference in age (p = 0.910) or baseline lumbar bone mineral density (BMD) (p = 0.998) found between any of the groups (pressfit, cemented, or trabecular). The pressfit implant initially behaved like the trabecular component with an immediate fall in BMD in the inferior and medial regions, with preserved BMD laterally, suggesting lateral rim loading. However, the pressfit component subsequently showed a reversal in BMD medially with recovery back towards baseline, and a continued rise in lateral BMD. This would suggest that the pressfit component begins to reload the medial bone over time, more akin to the cemented component. Analysis of postoperative radiographs revealed no pressfit component subsidence or movement up to two years postoperatively (100% interobserver reliability). Medial defects seen immediately postoperatively in five cases had completely resolved by two years in four patients. CONCLUSION: Initially, the uncemented monoblock component behaved similarly to the rigid trabecular metal component with lateral rim loading; however, over two years this changed to more closely resemble the loading pattern of a cemented polyethylene component with increasing medial pelvic loading. This indicates that the uncemented monoblock acetabular component may result in optimized fixation and preservation of retroacetabular bone stock. Cite this article: Bone Joint J 2021;103-B(5):872-880.

Sport after total hip arthroplasty: undoubted progress but still some unknowns.

In this review, we discuss the evidence for patients returning to sport after hip arthroplasty. This includes the choices regarding level of sporting activity and revision or complications, the type of implant, fixation and techniques of implantation, and how these choices relate to health economics. It is apparent that despite its success over six decades, hip arthroplasty has now evolved to accommodate and support ever-increasing patient demands and may therefore face new challenges. Cite this article: Bone Joint J 2020;102-B(6):661-663.

Investigation of Taper Failure in a Contemporary Metal-on-Metal Hip Arthroplasty System Through Examination of Unused and Explanted Prostheses.

BACKGROUND: Large-diameter (≥36-mm) metal-on-metal (MoM) total hip replacements have been shown to fail at an unacceptably high rate. Globally, the DePuy Pinnacle prosthesis was the most widely used device of this type. There is evidence to suggest that one of the main reasons for the poor clinical performance of large-diameter MoM prostheses is the metal debris released from the head-stem taper junction-i.e., taper junction failure. The aim of this study was to investigate variation in the as-manufactured finish of the female taper surface and to determine its influence on material loss. We hypothesized that rougher surfaces with higher relative material peaks would be significantly associated with greater taper wear rates. METHODS: We analyzed 93 Articul/eze femoral head tapers with a 36-mm bearing diameter that had been used in combination with a Corail titanium uncemented stem. The influence of the surface topography of the as-manufactured female taper surface on taper wear was examined by means of a multiple regression model, taking into account other known variables. RESULTS: We identified great variation in the as-manufactured surface finish of the female taper surface, with a range of measured Ra values from 0.14 to 4.20 µm. The roughness of the female taper surface appeared to be the most important variable associated with taper wear (p < 0.001). The best-fitting regression model, including duration in vivo, head offset, reduced peak height (Rpk) value, stem shaft angle, and bearing surface wear rate, explained approximately 44% of the variation in taper wear rates. CONCLUSIONS: We concluded that the roughness of the female taper surface appears to be a significant factor in metal debris release from head-stem taper junctions. CLINICAL RELEVANCE: This study shows evidence that previously unappreciated variations in manufacturing processes may have a major impact on the clinical outcomes of patients.

The Tribology of Explanted Hip Resurfacings Following Early Fracture of the Femur.

A recognized issue related to metal-on-metal hip resurfacings is early fracture of the femur. Most theories regarding the cause of fracture relate to clinical factors but an engineering analysis of failed hip resurfacings has not previously been reported. The objective of this work was to determine the wear volumes and surface roughness values of a cohort of retrieved hip resurfacings which were removed due to early femoral fracture, infection and avascular necrosis (AVN). Nine resurfacing femoral heads were obtained following early fracture of the femur, a further five were retrieved due to infection and AVN. All fourteen were measured for volumetric wear using a co-ordinate measuring machine. Wear rates were then calculated and regions of the articulating surface were divided into "worn" and "unworn". Roughness values in these regions were measured using a non-contacting profilometer. The mean time to fracture was 3.7 months compared with 44.4 months for retrieval due to infection and AVN. Average wear rates in the early fracture heads were 64 times greater than those in the infection and AVN retrievals. Given the high wear rates of the early fracture components, such wear may be linked to an increased risk of femoral neck fracture.

Inflammation and Neovascularization in Hip Impingement: Not Just Wear and Tear.

BACKGROUND: Femoroacetabular impingement (FAI) is a significant cause of osteoarthritis (OA) in young active patients, but the pathophysiology remains unclear. Increasingly, mechanistic studies point toward an inflammatory component in OA. PURPOSE: This study aimed to characterize inflammatory cell subtypes and neovascularization in FAI by exploring the phenotype and quantification of inflammatory cells and neovascularization in FAI versus OA samples. STUDY DESIGN: Descriptive laboratory study. METHODS: Ten samples of the labrum were obtained from patients with FAI (confirmed diagnosis) during open osteochondroplasty or hip arthroscopic surgery. Control samples of the labrum were collected from 10 patients with OA who were undergoing total hip arthroplasty. Labral biopsy specimens were evaluated immunohistochemically by quantifying the presence of macrophages (CD68, CD206, interleukin-13 [IL-13]), T cells (CD3), mast cells (mast cell tryptase), and vascular endothelium (CD34, vascular endothelial growth factor). RESULTS: Labral biopsy specimens obtained from patients with FAI exhibited significantly greater macrophage, mast cell, and vascular endothelium expression compared with control OA labral samples (P < .05). The most significant difference was noted in macrophage (P < .01) and mast cell (P < .05) expression. Further subtyping of macrophages in FAI using the CD206 tissue marker and IL-13 revealed an M2 phenotype, suggesting that these cells are involved in a regenerate versus degenerate process. There was a modest but significant correlation between mast cells and CD34 expression (r = 0.4, P < .01) in FAI samples. CONCLUSION: This study provides evidence for an inflammatory cell infiltrate in FAI along with significant neovascularization. In particular, the significant infiltration of mast cells and macrophages was demonstrated, suggesting a role for innate immune pathways in the events that mediate hip impingement. CLINICAL RELEVANCE: Further mechanistic studies to evaluate the net contribution and hence therapeutic utility of these cellular lineages and their downstream processes may reveal novel therapeutic approaches to the management of early hip impingement.

Draft Genome Sequence of Isolate Staphylococcus aureus LHSKBClinical, Isolated from an Infected Hip.

We report here the genome sequence of a clinical isolate of Staphylococcus aureus from an orthopedic infection. Phenotypically diverse Staphylococcus aureus strains are associated with orthopedic infections and subsequent implant failure, and some are highly resistant to antibiotics. This genome sequence will support further analyses of strains causing orthopedic infections.

Three-dimensional CaP/gelatin lattice scaffolds with integrated osteoinductive surface topographies for bone tissue engineering.

Surface topography is known to influence stem cells and has been widely used as physical stimuli to modulate cellular behaviour including adhesion, proliferation and differentiation on 2D surfaces. Integration of well-defined surface topography into three-dimensional (3D) scaffolds for tissue engineering would be useful to direct the cell fate for intended applications. Technical challenges are remaining as how to fabricate such 3D scaffolds with controlled surface topography from a range of biodegradable and biocompatible materials. In this paper, a novel fabrication process using computer numerically controlled machining and lamination is reported to make 3D calcium phosphate/gelatin composite scaffolds with integrated surface micropatterns that are introduced by embossing prior to machining. Geometric analysis shows that this method is versatile and can be used to make a wide range of lattices with porosities that meet the basic requirements for bone tissue engineering. Both in vitro and in vivo studies show that micropatterned composite scaffolds with surfaces comprising 40 µm pits and 50 µm grooves were optimal for improved osteogenesis. The results have demonstrated the potential of a novel fabrication process for producing cell-instructive scaffolds with designed surface topographies to induce specific tissue regeneration.

Nanotopology potentiates growth hormone signalling and osteogenesis of mesenchymal stem cells.

Custom engineered materials can influence the differentiation of human mesenchymal stem cells (MSCs) towards osteoblasts, chondrocytes and adipocytes, through the control of chemistry, stiffness and nanoscale topography. Here we demonstrate that polycaprolactone growth surfaces engineered with disordered (but controlled) 120 nm diameter dots (NSQ50), but not flat surfaces, promote osteogenic conversion of MSCs in the absence of other osteogenic stimuli. Differentiating MSCs on NSQ50 were found to express growth hormone receptors (GH) and stimulation with recombinant human GH (rhGH) further enhanced NSQ50-driven osteogenic conversion of MSCs. This increased osteogenesis coincided with an enhanced ability of GH to activate ERK MAP kinase on NSQ50, but not on flat topology. The importance of ERK for MSC differentiation was demonstrated by using the inhibitor of ERK activation, U0126, which completely suppressed osteogenesis of GH-stimulated MSCs on NSQ50. The ability of GH to activate ERK in MSCs may therefore be a central control mechanism underlying bone development and growth.

Nanotopographical induction of osteogenesis through adhesion, bone morphogenic protein cosignaling, and regulation of microRNAs.

It is emerging that nanotopographical information can be used to induce osteogenesis from mesenchymal stromal cells from the bone marrow, and it is hoped that this nanoscale bioactivity can be utilized to engineer next generation implants. However, the osteogenic mechanism of surfaces is currently poorly understood. In this report, we investigate mechanism and implicate bone morphogenic protein (BMP) in up-regulation of RUNX2 and show that RUNX2 and its regulatory miRNAs are BMP sensitive. Our data demonstrate that osteogenic nanotopography promotes colocalization of integrins and BMP2 receptors in order to enhance osteogenic activity and that vitronectin is important in this interface. This provides insight that topographical regulation of adhesion can have effects on signaling cascades outside of cytoskeletal signaling and that adhesions can have roles in augmenting BMP signaling.

2D and 3D nanopatterning of titanium for enhancing osteoinduction of stem cells at implant surfaces.

The potential for the use of well-defined nanopatterns to control stem cell behaviour on surfaces has been well documented on polymeric substrates. In terms of translation to orthopaedic applications, there is a need to develop nanopatterning techniques for clinically relevant surfaces, such as the load-bearing material titanium (Ti). In this work, a novel nanopatterning method for Ti surfaces is demonstrated, using anodisation in combination with PS-b-P4VP block copolymer templates. The block copolymer templates allows for fabrication of titania nanodot patterns with precisely controlled dimensions and positioning which means that this technique can be used as a lithography-like patterning method of bulk Ti surfaces on both flat 2D and complex shaped 3D surfaces. In vitro studies demonstrate that precise tuning of the height of titania nanodot patterns can modulate the osteogenic differentiation of mesenchymal stem cells. Cells on both the 8 nm and 15 nm patterned surfaces showed a trend towards a greater number of the large, super-mature osteogenic focal adhesions than on the control polished Ti surface, but the osteogenic effect was more pronounced on the 15 nm substrate. Cells on this surface had the longest adhesions of all and produced larger osteocalcin deposits. The results suggest that nanopatterning of Ti using the technique of anodisation through a block copolymer template could provide a novel way to enhance osteoinductivity on Ti surfaces.

Titanium nanofeaturing for enhanced bioactivity of implanted orthopedic and dental devices.

Titanium (Ti) is used as a load-bearing material in the production of orthopedic devices. The clinical efficacy of these implants could be greatly enhanced by the addition of nanofeatures that would improve the bioactivity of the implants, in order to promote in situ osteo-induction and -conduction of the patient's stem and osteoprogenitor cells, and to enhance osseointegration between the implant and the surrounding bone. Nanofeaturing of Ti is also currently being applied as a tool for the biofunctionalization of commercially available dental implants. In this review, we discuss the different nanofabrication strategies that are available to generate nanofeatures in Ti and the cellular response to the resulting nanofeatures. In vitro research, in vivo studies and clinical trials are considered, and we conclude with a perspective about the future potential for use of nanotopographical features in a therapeutic setting.

Does orthopaedic surgical training induce hypertension? A pilot study.

BACKGROUND: Elevated blood pressure (BP) is associated with increased cardiovascular risks manifested by ischemic heart disease and stroke. Studies of cardiothoracic surgeons and neurosurgeons suggest surgery induces a hemodynamic stress malresponse. However, it is unclear whether these occur in orthopaedic surgeons. QUESTIONS/PURPOSES: We measured the BP of surgeons during hallux valgus surgery, TKA, and THA with the: (1) trainee assisting the trainer, (2) the trainer assisting the trainee, (3) the trainee operating independently, and (4) compared the intraoperative changes in BP and heart rate of orthopaedic surgeons with those of a clinic day and during an exercise tolerance test. METHODS: We used an ambulatory BP monitor to measure the BP and heart rate of three consultants and their respective trainees during hallux valgus surgery, TKA, or THA. We noted if there were any differences in the stress response of the lead surgeon in comparison to when the same individual was assisting a trainee, and vice versa. Additionally, we recorded the trainee's BP and heart rate when they were operating independently. The intraoperative changes in BP and heart rate of orthopaedic surgeons were compared with those measured during a clinic day and during an exercise tolerance test. RESULTS: When the trainer was leading the operation, their mean arterial pressure gradually increased to 105 (range, 102-109) until implant placement. However, when the trainee was operating and the trainer assisting, the trainer's BP peaked (mean, 101; range, 95-111) at the beginning of the procedure and slowly declined as it progressed. The trainee's BP remained elevated throughout. The highest peaks for trainees were noted during independent operating. All of the surgeons had higher average BP readings (mean, 100; range, 95-108) and heart rate (mean, 86; range, 57-117) on days when they did surgery compared with baseline. CONCLUSIONS: The elective operations studied induced a hypertensive response. The response was more marked in trainees than in trainers, particularly if the trainee was operating independently.