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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). Results. Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular bone was present in 33.3% of the biomembrane specimens; bone presence did not correlate with spacer duration. Biomembrane morphology showed high vascularity and collagen content and positive staining for the key bone forming regulators, bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis was found in cells from patients with PMMA present for six to 17 weeks. Stem cell differentiation showed greater variability in pluripotency for osteogenic potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and 90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens, and bone gla protein was present in biomembrane compared with the cultured cell line. Biomembranes with longer resident PMMA spacer duration (vs those with shorter residence) showed significant upregulation of bone-related, stem cell, and vascular-related genes. Conclusion. The biomembrane technique is gaining favour in the management of complicated bone defects. Novel data on biological mechanisms provide improved understanding of the biomembrane’s osteogenic potential and molecular properties. Cite this article: Dr H. E. Gruber. Osteogenic, stem cell and molecular characterisation of the human induced membrane from extremity bone defects. Bone Joint Res 2016;5:106–115. DOI: 10.1302/2046-3758.54.2000483


Bone & Joint Research
Vol. 5, Issue 10 | Pages 512 - 519
1 Oct 2016
Mills L Tsang J Hopper G Keenan G Simpson AHRW

Objectives

A successful outcome following treatment of nonunion requires the correct identification of all of the underlying cause(s) and addressing them appropriately. The aim of this study was to assess the distribution and frequency of causative factors in a consecutive cohort of nonunion patients in order to optimise the management strategy for individual patients presenting with nonunion.

Methods

Causes of the nonunion were divided into four categories: mechanical; infection; dead bone with a gap; and host. Prospective and retrospective data of 100 consecutive patients who had undergone surgery for long bone fracture nonunion were analysed.


Bone & Joint Research
Vol. 5, Issue 10 | Pages 481 - 489
1 Oct 2016
Handoll HHG Brealey SD Jefferson L Keding A Brooksbank AJ Johnstone AJ Candal-Couto JJ Rangan A

Objectives

Accurate characterisation of fractures is essential in fracture management trials. However, this is often hampered by poor inter-observer agreement. This article describes the practicalities of defining the fracture population, based on the Neer classification, within a pragmatic multicentre randomised controlled trial in which surgical treatment was compared with non-surgical treatment in adults with displaced fractures of the proximal humerus involving the surgical neck.

Methods

The trial manual illustrated the Neer classification of proximal humeral fractures. However, in addition to surgical neck displacement, surgeons assessing patient eligibility reported on whether either or both of the tuberosities were involved. Anonymised electronic versions of baseline radiographs were sought for all 250 trial participants. A protocol, data collection tool and training presentation were developed and tested in a pilot study. These were then used in a formal assessment and classification of the trial fractures by two independent senior orthopaedic shoulder trauma surgeons.


Bone & Joint Research
Vol. 1, Issue 8 | Pages 174 - 179
1 Aug 2012
Alfieri KA Forsberg JA Potter BK

Heterotopic ossification (HO) is perhaps the single most significant obstacle to independence, functional mobility, and return to duty for combat-injured veterans of Operation Enduring Freedom and Operation Iraqi Freedom. Recent research into the cause(s) of HO has been driven by a markedly higher prevalence seen in these wounded warriors than encountered in previous wars or following civilian trauma. To that end, research in both civilian and military laboratories continues to shed light onto the complex mechanisms behind HO formation, including systemic and wound specific factors, cell lineage, and neurogenic inflammation. Of particular interest, non-invasive in vivo testing using Raman spectroscopy may become a feasible modality for early detection, and a wound-specific model designed to detect the early gene transcript signatures associated with HO is being tested. Through a combined effort, the goals of early detection, risk stratification, and development of novel systemic and local prophylaxis may soon be attainable.


Bone & Joint Research
Vol. 2, Issue 6 | Pages 112 - 115
1 Jun 2013
Ismail HD Phedy P Kholinne E Kusnadi Y Sandhow L Merlina M

Objectives

Nonunion is one of the most troublesome complications to treat in orthopaedics. Former authors believed that atrophic nonunion occurred as a result of lack of mesenchymal stem cells (MSCs). We evaluated the number and viability of MSCs in site of atrophic nonunion compared with those in iliac crest.

Methods

We enrolled five patients with neglected atrophic nonunions of long bones confirmed by clinical examinations and plain radiographs into this study. As much as 10 ml bone marrow aspirate was obtained from both the nonunion site and the iliac crest and cultured for three weeks. Cell numbers were counted using a haemocytometer and vitality of the cells was determined by trypan blue staining. The cells were confirmed as MSCs by evaluating their expression marker (CD 105, CD 73, HLA-DR, CD 34, CD 45, CD 14, and CD 19). Cells number and viability were compared between the nonunion and iliac creat sites.


Bone & Joint Research
Vol. 1, Issue 11 | Pages 289 - 296
1 Nov 2012
Savaridas T Wallace RJ Muir AY Salter DM Simpson AHRW

Objectives

Small animal models of fracture repair primarily investigate indirect fracture healing via external callus formation. We present the first described rat model of direct fracture healing.

Methods

A rat tibial osteotomy was created and fixed with compression plating similar to that used in patients. The procedure was evaluated in 15 cadaver rats and then in vivo in ten Sprague-Dawley rats. Controls had osteotomies stabilised with a uniaxial external fixator that used the same surgical approach and relied on the same number and diameter of screw holes in bone.


Bone & Joint Research
Vol. 1, Issue 3 | Pages 31 - 35
1 Mar 2012
Fowler JR Kleiner MT Das R Gaughan JP Rehman S

Introduction

Negative pressure wound therapy (NPWT) and vessel loop assisted closure are two common methods used to assist with the closure of fasciotomy wounds. This retrospective review compares these two methods using a primary outcome measurement of skin graft requirement.

Methods

A retrospective search was performed to identify patients who underwent fasciotomy at our institution. Patient demographics, location of the fasciotomy, type of assisted closure, injury characteristics, need for skin graft, length of stay and evidence of infection within 90 days were recorded.