Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells.

Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

Does delay to theatre influence morbidity or mortality in femoral periprosthetic fractures?

Aims: Femoral periprosthetic fractures are rising in incidence. Their management is complex and carries a high associated mortality. Unlike native hip fractures, there are no guidelines advising on time to theatre in this group. We aim to determine whether delaying surgical intervention influences morbidity or mortality in femoral periprosthetic fractures. Methods: We identified all periprosthetic fractures around a hip or knee arthroplasty from our prospectively collated database between 2012 and 2021. Patients were categorized into early or delayed intervention based on time from admission to surgery (early = ≤ 36 hours, delayed > 36 hours). Patient demographics, existing implants, Unified Classification System fracture subtype, acute medical issues on admission, preoperative haemoglobin, blood transfusion requirement, and length of hospital stay were identified for all patients. Complication and mortality rates were compared between groups. Results: A total of 365 patients were identified: 140 in the early and 225 in the delayed intervention group. Mortality rate was 4.1% at 30 days and 19.2% at one year. There was some indication that those who had surgery within 36 hours had a higher mortality rate, but this did not reach statistical significance at 30 days (p = 0.078) or one year (p = 0.051). Univariate analysis demonstrated that age, preoperative haemoglobin, acute medical issue on admission, and the presence of postoperative complications influenced 30-day and one-year mortality. Using a multivariate model, age and preoperative haemoglobin were independently predictive factors for one-year mortality (odds ratio (OR) 1.071; p < 0.001 and OR 0.980; p = 0.020). There was no association between timing of surgery and postoperative complications. Postoperative complications were more likely with increasing age (OR 1.032; p = 0.001) and revision arthroplasty compared to internal fixation (OR 0.481; p = 0.001). Conclusion: While early intervention may be preferable to reduce prolonged immobilization, there is no evidence that delaying surgery beyond 36 hours increases mortality or complications in patients with a femoral periprosthetic fracture.

Proceedings of the United Kingdom Periprosthetic Joint Infection Meeting 2022: Combined and Arthroplasty Sessions.

Considerable variation in practice exists in the prevention, diagnosis, and treatment of periprosthetic joint infection (PJI), which is a devastating complication for patients and surgeons. The consensus principle has been increasingly embraced by the orthopaedic community to help guide practice, especially where high-level evidence remains unavailable. The third United Kingdom Periprosthetic Joint Infection (UK PJI) Meeting was held in Glasgow on April 1, 2022, with more than 180 delegates in attendance, representing orthopaedics, microbiology, infectious diseases, plastic surgery, anesthetics, and allied health professions, including pharmacy and arthroplasty nurses. The meeting comprised a combined session for all delegates, and separate breakout sessions for arthroplasty and fracture-related infection. Consensus questions for each session were prepared in advance by the UK PJI working group, based upon topics that were proposed at previous UK PJI Meetings, and delegates participated in an anonymized electronic voting process. We present the findings of the combined and arthroplasty sessions of the meeting in this article, and each consensus topic is discussed in relation to the contemporary literature.

Consultant revision hip arthroplasty volumes and new consultant volume trajectories in England, Wales, Northern Ireland, and the Isle of Man.

Aims: This study describes the variation in the annual volumes of revision hip arthroplasty (RHA) undertaken by consultant surgeons nationally, and the rate of accrual of RHA and corresponding primary hip arthroplasty (PHA) volume for new consultants entering practice. Methods: National Joint Registry (NJR) data for England, Wales, Northern Ireland, and the Isle of Man were received for 84,816 RHAs and 818,979 PHAs recorded between April 2011 and December 2019. RHA data comprised all revision procedures, including first-time revisions of PHA and any subsequent re-revisions recorded in public and private healthcare organizations. Annual procedure volumes undertaken by the responsible consultant surgeon in the 12 months prior to every index procedure were determined. We identified a cohort of 'new' HA consultants who commenced practice from 2012 and describe their rate of accrual of PHA and RHA experience. Results: The median annual consultant RHA volume, averaged across all cases, was 21 (interquartile range (IQR) 11 to 34; range 0 to 181). Of 1,695 consultants submitting RHA cases within the study period, the top 20% of surgeons by annual volume performed 74.2% of total RHA case volume. More than half of all consultants who had ever undertaken a RHA maintained an annual volume of just one or fewer RHA, however, collectively contributed less than 3% of the total RHA case volume. Consultant PHA and RHA volumes were positively correlated. Lower-volume surgeons were more likely to undertake RHA for urgent indications (such as infection) as a proportion of their practice, and to do so on weekends and public holidays. Conclusion: The majority of RHAs were undertaken by higher-volume surgeons. There was considerable variation in RHA volumes by indication, day of the week, and between consultants nationally. The rate of accrual of RHA experience by new consultants is low, and has important implications for establishing an experienced RHA consultant workforce.

Periprosthetic joint infection: what next?

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.Cite this article: Bone Joint J 2022;104-B(11):1193-1195.

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.

Bdellovibrio bacteriovorus phosphoglucose isomerase structures reveal novel rigidity in the active site of a selected subset of enzymes upon substrate binding.

Glycolysis and gluconeogenesis are central pathways of metabolism across all domains of life. A prominent enzyme in these pathways is phosphoglucose isomerase (PGI), which mediates the interconversion of glucose-6-phosphate and fructose-6-phosphate. The predatory bacterium Bdellovibrio bacteriovorus leads a complex life cycle, switching between intraperiplasmic replicative and extracellular 'hunter' attack-phase stages. Passage through this complex life cycle involves different metabolic states. Here we present the unliganded and substrate-bound structures of the B. bacteriovorus PGI, solved to 1.74 Å and 1.67 Å, respectively. These structures reveal that an induced-fit conformational change within the active site is not a prerequisite for the binding of substrates in some PGIs. Crucially, we suggest a phenylalanine residue, conserved across most PGI enzymes but substituted for glycine in B. bacteriovorus and other select organisms, is central to the induced-fit mode of substrate recognition for PGIs. This enzyme also represents the smallest conventional PGI characterized to date and probably represents the minimal requirements for a functional PGI.

Improving outcomes in acute and chronic periprosthetic hip and knee joint infection with a multidisciplinary approach.

AIMS: Periprosthetic hip and knee infection remains one of the most severe complications following arthroplasty, with an incidence between 0.5% to 1%. This study compares the outcomes of revision surgery for periprosthetic joint infection (PJI) following hip and knee arthroplasty prior to and after implementation of a specialist PJI multidisciplinary team (MDT). METHODS: Data was retrospectively analyzed from a single centre. In all, 29 consecutive joints prior to the implementation of an infection MDT in November 2016 were compared with 29 consecutive joints subsequent to the MDT conception. All individuals who underwent a debridement antibiotics and implant retention (DAIR) procedure, a one-stage revision, or a two-stage revision for an acute or chronic PJI in this time period were included. The definition of successfully treated PJI was based on the Delphi international multidisciplinary consensus. RESULTS: There were no statistically significant differences in patient demographics or comorbidities between the groups. There was also no significant difference in length of overall hospital stay (p = 0.530). The time taken for formal microbiology advice was significantly shorter in the post MDT group (p = 0.0001). There was a significant difference in failure rates between the two groups (p = 0.001), with 12 individuals (41.38%) pre-MDT requiring further revision surgery compared with one individual (6.67%) post-MDT inception. CONCLUSION: Our standardized multidisciplinary approach for periprosthetic knee and hip joint infection shows a significant reduction in failure rates following revision surgery. Following implementation of our MDT, our success rate in treating PJI is 96.55%, higher than what current literature suggests. We advocate the role of a specialist infection MDT in the management of patients with a PJI to allow an individualized patient-centred approach and care plan, thereby reducing postoperative complications and failure rates. Cite this article: Bone Jt Open 2021;2(7):509-514.

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.

Outcomes of modular femoral revision implants and the effect of component design on subsidence.

AIMS: Femoral revision component subsidence has been identified as predicting early failure in revision hip surgery. This comparative cohort study assessed the potential risk factors of subsidence in two commonly used femoral implant designs. METHODS: A comparative cohort study was undertaken, analyzing a consecutive series of patients following revision total hip arthroplasties using either a tapered-modular (TM) fluted titanium or a porous-coated cylindrical modular (PCM) titanium femoral component, between April 2006 and May 2018. Clinical and radiological assessment was compared for both treatment cohorts. Risk factors for subsidence were assessed and compared. RESULTS: In total, 65 TM and 35 PCM cases were included. At mean follow-up of seven years (1 to 13), subsidence was noted in both cohorts during the initial three months postoperatively (p < 0.001) then implants stabilized. Subsidence noted in 58.7% (38/65 cases) of the TM cohort (mean 2.3 mm, SD 3.5 mm) compared to 48.8% (17/35) of PCM cohort (mean 1.9 mm, SD 2.6 mm; p = 0.344). Subsidence of PCM cohort were significantly associated with extended trochanteric osteotomy (ETO) (p < 0.041). Although the ETO was used less frequently in PCM stem cohort (7/35), subsidence was noted in 85% (6/7) of them. Significant improvement of the final mean Oxford Hip Score (OHS) was reported in both treatment groups (p < 0.001). CONCLUSION: Both modular TM and PCM revision femoral components subsided within the femur. TM implants subsided more frequently than PCM components if the femur was intact but with no difference in clinical outcomes. However, if an ETO is performed then a PCM component will subside significantly more and suggests the use of a TM implant may be advisable. Cite this article: Bone Joint J 2020;102-B(6):709-715.

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.