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The Bone & Joint Journal
Vol. 97-B, Issue 3 | Pages 318 - 323
1 Mar 2015
Verdonk P Dhollander A Almqvist KF Verdonk R Victor J

The treatment of osteochondral lesions is of great interest to orthopaedic surgeons because most lesions do not heal spontaneously. We present the short-term clinical outcome and MRI findings of a cell-free scaffold used for the treatment of these lesions in the knee. A total of 38 patients were prospectively evaluated clinically for two years following treatment with an osteochondral nanostructured biomimetic scaffold. There were 23 men and 15 women; the mean age of the patients was 30.5 years (15 to 64). Clinical outcome was assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS), the Tegner activity scale and a Visual Analgue scale for pain. MRI data were analysed based on the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scoring system at three, 12 and 24 months post-operatively. There was a continuous significant clinical improvement after surgery. In two patients, the scaffold treatment failed (5.3%) There was a statistically significant improvement in the MOCART precentage scores. The repair tissue filled most of the defect sufficiently. We found subchondral laminar changes in all patients. Intralesional osteophytes were found in two patients (5.3%). We conclude that this one-step scaffold-based technique can be used for osteochondral repair. The surgical technique is straightforward, and the clinical results are promising. The MRI aspects of the repair tissue continue to evolve during the first two years after surgery. However, the subchondral laminar and bone changes are a concern.

Cite this article: Bone Joint J 2015; 97-B:318–23.


The Bone & Joint Journal
Vol. 95-B, Issue 11 | Pages 1544 - 1550
1 Nov 2013
Uchiyama S Itsubo T Nakamura K Fujinaga Y Sato N Imaeda T Kadoya M Kato H

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (se 0.16)) and the no-ALN group (3.1 months (se 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically.

Cite this article: Bone Joint J 2013;95-B:1544–50.


Bone & Joint Research
Vol. 1, Issue 7 | Pages 158 - 166
1 Jul 2012
Dean BJF Franklin SL Carr AJ

Introduction

The pathogenesis of rotator cuff disease (RCD) is complex and not fully understood. This systematic review set out to summarise the histological and molecular changes that occur throughout the spectrum of RCD.

Methods

We conducted a systematic review of the scientific literature with specific inclusion and exclusion criteria.


The Bone & Joint Journal
Vol. 97-B, Issue 10 | Pages 1423 - 1427
1 Oct 2015
Rand BCC Penn-Barwell JG Wenke JC

Systemic antibiotics reduce infection in open fractures. Local delivery of antibiotics can provide higher doses to wounds without toxic systemic effects. This study investigated the effect on infection of combining systemic with local antibiotics via polymethylmethacrylate (PMMA) beads or gel delivery.

An established Staphylococcus aureus contaminated fracture model in rats was used. Wounds were debrided and irrigated six hours after contamination and animals assigned to one of three groups, all of which received systemic antibiotics. One group had local delivery via antibiotic gel, another PMMA beads and the control group received no local antibiotics. After two weeks, bacterial levels were quantified.

Combined local and systemic antibiotics were superior to systemic antibiotics alone at reducing the quantity of bacteria recoverable from each group (p = 0.002 for gel; p = 0.032 for beads). There was no difference in the bacterial counts between bead and gel delivery (p = 0.62).

These results suggest that local antibiotics augment the antimicrobial effect of systemic antibiotics. Although no significant difference was found between vehicles, gel delivery offers technical advantages with its biodegradable nature, ability to conform to wound shape and to deliver increased doses. Further study is required to see if the gel delivery system has a clinical role.

Cite this article: Bone Joint J 2015;97-B:1423–7.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 203 - 211
1 Jun 2014
Onur T Wu R Metz L Dang A

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

Methods

T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis.


Bone & Joint Research
Vol. 5, Issue 4 | Pages 106 - 115
1 Apr 2016
Gruber HE Ode G Hoelscher G Ingram J Bethea S Bosse MJ

Objectives

The biomembrane (induced membrane) formed around polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone defect reconstruction. Few studies have evaluated its cellular, molecular or stem cell features. Our objective was to characterise induced membrane morphology, molecular features and osteogenic stem cell characteristics.

Methods

Following Institutional Review Board approval, biomembrane specimens were obtained from 12 patient surgeries for management of segmental bony defects (mean patient age 40.7 years, standard deviation 14.4). Biomembranes from nine tibias and three femurs were processed for morphologic, molecular or stem cell analyses. Gene expression was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular analyses compared biomembrane gene expression patterns with a mineralising osteoblast culture, and gene expression in specimens with longer spacer duration (> 12 weeks) with specimens with shorter durations. Statistical analyses used the unpaired student t-test (two tailed; p < 0.05 was considered significant).


The Bone & Joint Journal
Vol. 95-B, Issue 3 | Pages 305 - 313
1 Mar 2013
Ribbans WJ Collins M

The incidence of acute and chronic conditions of the tendo Achillis appear to be increasing. Causation is multifactorial but the role of inherited genetic elements and the influence of environmental factors altering gene expression are increasingly being recognised. Certain individuals’ tendons carry specific variations of genetic sequence that may make them more susceptible to injury. Alterations in the structure or relative amounts of the components of tendon and fine control of activity within the extracellular matrix affect the response of the tendon to loading with failure in certain cases.

This review summarises present knowledge of the influence of genetic patterns on the pathology of the tendo Achillis, with a focus on the possible biological mechanisms by which genetic factors are involved in the aetiology of tendon pathology. Finally, we assess potential future developments with both the opportunities and risks that they may carry.

Cite this article: Bone Joint J 2013;95-B:305–13.


Bone & Joint Research
Vol. 3, Issue 3 | Pages 51 - 59
1 Mar 2014
Kim HJ Braun HJ Dragoo JL

Background

Resveratrol is a polyphenolic compound commonly found in the skins of red grapes. Sirtuin 1 (SIRT1) is a human gene that is activated by resveratrol and has been shown to promote longevity and boost mitochondrial metabolism. We examined the effect of resveratrol on normal and osteoarthritic (OA) human chondrocytes.

Methods

Normal and OA chondrocytes were incubated with various concentrations of resveratrol (1 µM, 10 µM, 25 µM and 50 µM) and cultured for 24, 48 or 72 hours or for six weeks. Cell proliferation, gene expression, and senescence were evaluated.


Bone & Joint Research
Vol. 2, Issue 2 | Pages 18 - 25
1 Feb 2013
Kon E Filardo G Di Matteo B Perdisa F Marcacci M

Objectives

Matrix-assisted autologous chondrocyte transplantation (MACT) has been developed and applied in the clinical practice in the last decade to overcome most of the disadvantages of the first generation procedures. The purpose of this systematic review is to document and analyse the available literature on the results of MACT in the treatment of chondral and osteochondral lesions of the knee.

Methods

All studies published in English addressing MACT procedures were identified, including those that fulfilled the following criteria: 1) level I-IV evidence, 2) measures of functional or clinical outcome, 3) outcome related to cartilage lesions of the knee cartilage.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 1033 - 1040
1 Jul 2010
Nishino T Chang F Ishii T Yanai T Mishima H Ochiai N

We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.


Bone & Joint Research
Vol. 3, Issue 9 | Pages 262 - 272
1 Sep 2014
Gumucio J Flood M Harning J Phan A Roche S Lynch E Bedi A Mendias C

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

Methods

A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation.


The Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 54 - 58
1 Jan 2014
Vijayan S Bentley G Rahman J Briggs TWR Skinner JA Carrington RWJ

The management of failed autologous chondrocyte implantation (ACI) and matrix-assisted autologous chondrocyte implantation (MACI) for the treatment of symptomatic osteochondral defects in the knee represents a major challenge. Patients are young, active and usually unsuitable for prosthetic replacement. This study reports the results in patients who underwent revision cartilage transplantation of their original ACI/MACI graft for clinical or graft-related failure. We assessed 22 patients (12 men and 10 women) with a mean age of 37.4 years (18 to 48) at a mean of 5.4 years (1.3 to 10.9). The mean period between primary and revision grafting was 46.1 months (7 to 89). The mean defect size was 446.6 mm2 (150 to 875) and they were located on 11 medial and two lateral femoral condyles, eight patellae and one trochlea.

The mean modified Cincinnati knee score improved from 40.5 (16 to 77) pre-operatively to 64.9 (8 to 94) at their most recent review (p < 0.001). The visual analogue pain score improved from 6.1 (3 to 9) to 4.7 (0 to 10) (p = 0.042). A total of 14 patients (63%) reported an ‘excellent’ (n = 6) or ‘good’ (n = 8) clinical outcome, 5 ‘fair’ and one ‘poor’ outcome. Two patients underwent patellofemoral joint replacement. This study demonstrates that revision cartilage transplantation after primary ACI and MACI can yield acceptable functional results and continue to preserve the joint.

Cite this article: Bone Joint J 2014;96-B:54–8.


The Bone & Joint Journal
Vol. 96-B, Issue 3 | Pages 291 - 298
1 Mar 2014
Murray IR Corselli M Petrigliano FA Soo C Péault B

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.


The Bone & Joint Journal
Vol. 95-B, Issue 8 | Pages 1022 - 1026
1 Aug 2013
O’Neill SC Queally JM Devitt BM Doran PP O’Byrne JM

Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis.

In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition.

Cite this article: Bone Joint J 2013;95-B:1021–5.


Bone & Joint 360
Vol. 2, Issue 1 | Pages 2 - 5
1 Feb 2013
Khan M Roberts S Richardson JB McCaskie A

Stem cells are a key component of regenerative medicine strategies. Particular areas of musculoskeletal application include cartilage and bone regeneration in arthritis and trauma. There are several types of stem cell and this article will focus on the adult derived cells. The review includes current issues and future developments.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 721 - 729
1 May 2005
Yanai T Ishii T Chang F Ochiai N

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel.

The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 12 | Pages 1575 - 1578
1 Dec 2009
Jaiswal PK Macmull S Bentley G Carrington RWJ Skinner JA Briggs TWR

Smoking is known to have an adverse effect on wound healing and musculoskeletal conditions. This case-controlled study looked at whether smoking has a deleterious effect in the outcome of autologous chondrocyte implantation for the treatment of full thickness chondral defects of the knee.

The mean Modified Cincinatti Knee score was statistically significantly lower in smokers (n = 48) than in non-smokers (n = 66) both before and after surgery (p < 0.05). Smokers experienced significantly less improvement in the knee score two years after surgery (p < 0.05). Graft failures were only seen in smokers (p = 0.016). There was a strong negative correlation between the number of cigarettes smoked and the outcome following surgery (Pearson’s correlation coefficient −0.65, p = 0.004).

These results suggest that patients who smoke have worse pre-operative function and obtain less benefit from this procedure than non-smokers. The counselling of patients undergoing autologous chondrocyte implantation should include smoking, not only as a general cardiopulmonary risk but also because poorer results can be expected in smokers following this procedure.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 8 | Pages 987 - 996
1 Aug 2009
Alsousou J Thompson M Hulley P Noble A Willett K

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches.

The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research.


Bone & Joint Research
Vol. 1, Issue 1 | Pages 1 - 7
1 Jan 2012
Rosenberg N Rosenberg O

Objectives

The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation.

Methods

Human osteoblast-like cells were seeded on porous granules of tricalcium phosphate and incubated in osteogenic media while exposed to mechanical stimulation by vibration in the infrasonic range of frequencies. The generated tissue was examined microscopically following haematoxylin eosin, trichrome and immunohistochemical staining.


The Bone & Joint Journal
Vol. 96-B, Issue 4 | Pages 508 - 512
1 Apr 2014
van Amerongen EA Creemers LB Kaoui N Bekkers JEJ Kon M Schuurman AH

Damage to the cartilage of the distal radioulnar joint frequently leads to pain and limitation of movement, therefore repair of this joint cartilage would be highly desirable. The purpose of this study was to investigate the fixation of scaffold in cartilage defects of this joint as part of matrix-assisted regenerative autologous cartilage techniques. Two techniques of fixation of collagen scaffolds, one involving fibrin glue alone and one with fibrin glue and sutures, were compared in artificially created cartilage defects of the distal radioulnar joint in a human cadaver. After being subjected to continuous passive rotation, the methods of fixation were evaluated for cover of the defect and pull out force.

No statistically significant differences were found between the two techniques for either cover of the defect or integrity of the scaffold. However, a significantly increased mean pull out force was found for the combined procedure, 0.665 N (0.150 to 1.160) versus 0.242 N (0.060 to 0.730) for glue fixation (p = 0.001).

This suggests that although successful fixation of a collagen type I/III scaffold in a distal radioulnar joint cartilage defect is feasible with both forms of fixation, fixation with glue and sutures is preferable.

Cite this article: Bone Joint J 2014;96-B:508–12.