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Bone & Joint Research
Vol. 7, Issue 4 | Pages 263 - 273
1 Apr 2018
Ferreira E Porter RM

Large bone defects remain a tremendous clinical challenge. There is growing evidence in support of treatment strategies that direct defect repair through an endochondral route, involving a cartilage intermediate. While culture-expanded stem/progenitor cells are being evaluated for this purpose, these cells would compete with endogenous repair cells for limited oxygen and nutrients within ischaemic defects. Alternatively, it may be possible to employ extracellular vesicles (EVs) secreted by culture-expanded cells for overcoming key bottlenecks to endochondral repair, such as defect vascularization, chondrogenesis, and osseous remodelling. While mesenchymal stromal/stem cells are a promising source of therapeutic EVs, other donor cells should also be considered. The efficacy of an EV-based therapeutic will likely depend on the design of companion scaffolds for controlled delivery to specific target cells. Ultimately, the knowledge gained from studies of EVs could one day inform the long-term development of synthetic, engineered nanovesicles. In the meantime, EVs harnessed from in vitro cell culture have near-term promise for use in bone regenerative medicine. This narrative review presents a rationale for using EVs to improve the repair of large bone defects, highlights promising cell sources and likely therapeutic targets for directing repair through an endochondral pathway, and discusses current barriers to clinical translation.

Cite this article: E. Ferreira, R. M. Porter. Harnessing extracellular vesicles to direct endochondral repair of large bone defects. Bone Joint Res 2018;7:263–273. DOI: 10.1302/2046-3758.74.BJR-2018-0006.


The Bone & Joint Journal
Vol. 100-B, Issue 5 | Pages 624 - 633
1 May 2018
Maredza M Petrou S Dritsaki M Achten J Griffin J Lamb SE Parsons NR Costa ML

Aim

The aim of this study was to compare the cost-effectiveness of intramedullary nail fixation and ‘locking’ plate fixation in the treatment of extra-articular fractures of the distal tibia.

Patients and Methods

An economic evaluation was conducted from the perspective of the United Kingdom National Health Service (NHS) and personal social services (PSS), based on evidence from the Fixation of Distal Tibia Fractures (UK FixDT) multicentre parallel trial. Data from 321 patients were available for analysis. Costs were collected prospectively over the 12-month follow-up period using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality adjusted life year (QALY) gained, and net monetary benefit. Sensitivity analyses were conducted to test the robustness of cost-effectiveness estimates.


The Bone & Joint Journal
Vol. 100-B, Issue 2 | Pages 190 - 196
1 Feb 2018
Chraim M Krenn S Alrabai HM Trnka H Bock P

Aims

Hindfoot arthrodesis with retrograde intramedullary nailing has been described as a surgical strategy to reconstruct deformities of the ankle and hindfoot in patients with Charcot arthropathy. This study presents case series of Charcot arthropathy patients treated with two different retrograde intramedullary straight compression nails in order to reconstruct the hindfoot and assess the results over a mid-term follow-up.

Patients and Methods

We performed a retrospective analysis of 18 consecutive patients and 19 operated feet with Charcot arthropathy who underwent a hindfoot arthrodesis using a retrograde intramedullary compression nail. Patients were ten men and eight women with a mean age of 63.43 years (38.5 to 79.8). We report the rate of limb salvage, complications requiring additional surgery, and fusion rate in both groups. The mean duration of follow-up was 46.36 months (37 to 70).


Bone & Joint Research
Vol. 5, Issue 10 | Pages 500 - 511
1 Oct 2016
Raina DB Gupta A Petersen MM Hettwer W McNally M Tägil M Zheng M Kumar A Lidgren L

Objectives

We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells.

Materials and Methods

We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.


Bone & Joint 360
Vol. 6, Issue 6 | Pages 14 - 16
1 Dec 2017


The Bone & Joint Journal
Vol. 99-B, Issue 2 | Pages 225 - 230
1 Feb 2017
Olsen LL Møller AM Brorson S Hasselager RB Sort R

Aims

Lifestyle risk factors are thought to increase the risk of infection after acute orthopaedic surgery but the evidence is scarce. We aimed to investigate whether smoking, obesity and alcohol overuse are risk factors for the development of infections after surgery for a fracture of the ankle.

Patients and Methods

We retrospectively reviewed all patients who underwent internal fixation of a fracture of the ankle between 2008 and 2013. The primary outcome was the rate of deep infection and the secondary outcome was any surgical site infection (SSI). Associations with the risk factors and possible confounding variables were analysed univariably and multivariably with backwards elimination.


The Bone & Joint Journal
Vol. 98-B, Issue 1_Supple_A | Pages 18 - 22
1 Jan 2016
Heller S Rezapoor M Parvizi J

The purpose of this article is to provide the reader with a seven-step checklist that could help in minimising the risk of PJI. The check list includes strategies that can be implemented pre-operatively such as medical optimisation, and reduction of the bioburden by effective skin preparation or actions taking during surgery such as administration of timely and appropriate antibiotics or blood conservation, and finally implementation of post-operative protocols such as efforts to minimise wound drainage and haematoma formation.

Cite this article: Bone Joint J 2016;98-B(1 Suppl A):18–22.


The Bone & Joint Journal
Vol. 99-B, Issue 11 | Pages 1502 - 1507
1 Nov 2017
Hong CC Tan JH Lim SH Nather A

Aims

Limb salvage for diabetic foot infections often require multiple procedures. Some patients will eventually end up with below knee amputation (BKA) when all limb salvage attempts fail. We seek to study the patients’ ability to return to normal life, functional status, prosthesis usage and perspectives on multiple limb salvage procedures that culminated in BKA to review if they would undertake a similar path if their situation was repeated.

Patients and Methods

A total of 41 patients who underwent BKA between July 2011 and June 2013 were reviewed. They were divided into primary and creeping (prior multiple salvage procedures) amputations. The Barthel’s Index (BI) and the Reintegration to Normal Living Index (RNLI) were used. A questionnaire was used to identify whether the patient would undergo the same multiple attempts at limb salvage again if faced with the same problem.


Bone & Joint 360
Vol. 5, Issue 3 | Pages 2 - 6
1 Jun 2016
Raglan M Scammell B


The Bone & Joint Journal
Vol. 98-B, Issue 5 | Pages 660 - 665
1 May 2016
Jung HJ Song JH Kekatpure AL Adikrishna A Hong HP Lee WJ Chun JM Jeon IH

Aims

The treatment of septic arthritis of the shoulder is challenging. The infection frequently recurs and the clinical outcome can be very poor. We aimed to review the outcomes following the use of continuous negative pressure after open debridement with a large diameter drain in patients with septic arthritis of the shoulder.

Patients and Methods

A total of 68 consecutive patients with septic arthritis of the shoulder underwent arthrotomy, irrigation and debridement. A small diameter suction drain was placed in the glenohumeral joint and a large diameter drain was placed in the subacromial space with continuous negative pressure of 15 cm H2O. All patients received a standardised protocol of antibiotics for a mean of 5.1 weeks (two to 11.1).


The Bone & Joint Journal
Vol. 98-B, Issue 12 | Pages 1697 - 1703
1 Dec 2016
Gilg MM Gaston CL Parry MC Jeys L Abudu A Tillman RM Carter SR Grimer RJ

Aims

Extendible endoprostheses have been available for more than 30 years and have become more sophisticated with time. The latest generation is ‘non-invasive’ and can be lengthened with an external magnetic force. Early results have shown a worryingly high rate of complications such as infection. This study investigates the incidence of complications and the need for further surgery in a cohort of patients with a non-invasive growing endoprosthesis.

Patients and Methods

Between 2003 and June 2014, 50 children (51 prostheses) had a non-invasive growing prosthesis implanted for a primary bone sarcoma. The minimum follow-up was 24 months for those who survived. Their mean age was 10.4 years (6 to 14). The incidence of complications and further surgery was documented.


Bone & Joint 360
Vol. 4, Issue 5 | Pages 15 - 16
1 Oct 2015

The October 2015 Foot & Ankle Roundup360 looks at: TightRope in Weber C fractures; A second look at the TightRope; Incisional VAC comes of age?; Platelet-derived growth factor and ankle fusions; Achilles tendon rehab in the longer term following surgery; Telemedicine for diabetic foot ulcer


The Bone & Joint Journal
Vol. 99-B, Issue 9 | Pages 1204 - 1209
1 Sep 2017
Fawi HMT Saba K Cunningham A Masud S Lewis M Hossain M Chopra I Ahuja S

Aims

To evaluate the incidence of primary venous thromboembolism (VTE), epidural haematoma, surgical site infection (SSI), and 90-day mortality after elective spinal surgery, and the effect of two protocols for prophylaxis.

Patients and Methods

A total of 2181 adults underwent 2366 elective spinal procedures between January 2007 and January 2012. All patients wore anti-embolic stockings, mobilised early and were kept adequately hydrated. In addition, 29% (689) of these were given low molecular weight heparin (LMWH) while in hospital. SSI surveillance was undertaken using the Centers for Disease Control and Prevention criteria.


Bone & Joint 360
Vol. 6, Issue 4 | Pages 16 - 18
1 Aug 2017


The Bone & Joint Journal
Vol. 98-B, Issue 8 | Pages 1011 - 1013
1 Aug 2016
Masters JPM Nanchahal J Costa ML


The Bone & Joint Journal
Vol. 98-B, Issue 10 | Pages 1418 - 1424
1 Oct 2016
Salandy A Malhotra K Goldberg AJ Cullen N Singh D

Aims

Smoking is associated with post-operative complications but smokers often under-report the amount they smoke. Our objective was to determine whether a urine dipstick test could be used as a substitute for quantitative cotinine assays to determine smoking status in patients.

Patients and Methods

Between September 2013 and July 2014 we conducted a prospective cohort study in which 127 consecutive patients undergoing a planned foot and ankle arthrodesis or osteotomy were included. Patients self-reported their smoking status and were classified as: ‘never smoked’ (61 patients), ‘ex-smoker’ (46 patients), or ‘current smoker’ (20 patients). Urine samples were analysed with cotinine assays and cotinine dipstick tests.


The Bone & Joint Journal
Vol. 98-B, Issue 9 | Pages 1197 - 1201
1 Sep 2016
Ashman BD Kong C Wing KJ Penner MJ Bugler KE White TO Younger ASE

Aims

Patients with diabetes are at increased risk of wound complications after open reduction and internal fixation of unstable ankle fractures. A fibular nail avoids large surgical incisions and allows anatomical reduction of the mortise.

Patients and Methods

We retrospectively reviewed the results of fluoroscopy-guided reduction and percutaneous fibular nail fixation for unstable Weber type B or C fractures in 24 adult patients with type 1 or type 2 diabetes. The re-operation rate for wound dehiscence or other indications such as amputation, mortality and functional outcomes was determined.


Bone & Joint 360
Vol. 6, Issue 4 | Pages 10 - 13
1 Aug 2017


Bone & Joint Research
Vol. 6, Issue 9 | Pages 535 - 541
1 Sep 2017
Zan P Mol MO Yao JJ Fan L Yang D Liu K Li G

Objectives

The length of the tourniquet time during total knee arthroplasty (TKA) is related to the incidence of post-operative deep vein thrombosis (DVT). Our aim in this study was to investigate the effect of the early release of the tourniquet on the incidence of DVT in patients undergoing TKA.

Methods

A total of 200 patients who underwent TKA between November 2015 and November 2016 were prospectively enrolled. The tourniquet was inflated before surgery and released immediately after the introduction of the components (early release group). This group was compared with a retrospective cohort of 200 primary TKAs, in which the tourniquet was released after the dressings had been applied (late release group). The presence of a DVT was detected using bilateral lower limb ultrasonography. Peri-operative clinical and follow-up data were collected for analysis.


The Bone & Joint Journal
Vol. 99-B, Issue 10 | Pages 1354 - 1365
1 Oct 2017
Patrick S McDowell A Lee A Frau A Martin U Gardner E McLorinan G Eames N

Aims

The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery.

Patients and Methods

A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery.

For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection.